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Sample records for tissue drug concentrations

  1. Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

    Science.gov (United States)

    Tylutki, Zofia; Polak, Sebastian

    2015-03-12

    Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

    Science.gov (United States)

    Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.; Vashakidze, Sergo

    2017-01-01

    ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

  3. Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

    Science.gov (United States)

    Kempker, Russell R; Heinrichs, M Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A; Blumberg, Henry M; Vashakidze, Sergo

    2017-06-01

    Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

  4. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    Energy Technology Data Exchange (ETDEWEB)

    Ozolinš, Terence R.S., E-mail: ozolinst@queensu.ca [Department of Biomedical and Molecular Sciences, Program in Pharmacology and Toxicology, Queen’s University, Botterell Hall, Kingston, ON K7L 3N6 (Canada); Weston, Andrea D. [Currently at Applied Biotechnology/Lead Discovery, Bristol-Myers Squibb, 5 Research Pkwy Wallingford, CT 06492-1996 (United States); Perretta, Anthony [Currently at Pfizer Research and Development, Eastern Point Road, Groton, CT 06340 (United States); Thomson, Jason J. [Currently at Yale Stem Cell Center, Yale School of Medicine, PO Box 208073, New Haven, CT 06520-8073 (United States); Brown, Nigel A. [Division of Basic Medical Sciences, St. George’s University of London, UK SW17 0RE (United Kingdom)

    2015-11-15

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  5. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    International Nuclear Information System (INIS)

    Ozolinš, Terence R.S.; Weston, Andrea D.; Perretta, Anthony; Thomson, Jason J.; Brown, Nigel A.

    2015-01-01

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  6. Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy

    Science.gov (United States)

    Ong, Yi Hong; Padawer-Curry, Jonah; Finlay, Jarod C.; Kim, Michele M.; Dimofte, Andreea; Cengel, Keith; Zhu, Timothy C.

    2018-02-01

    PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption μa (λ) and scattering μs ' (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%StO2), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

  7. Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

    1983-03-01

    A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

  8. Drugs Approved for Soft Tissue Sarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for soft tissue sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  9. Methamphetamine and amphetamine concentrations in postmortem rabbit tissues.

    Science.gov (United States)

    Nagata, T; Kimura, K; Hara, K; Kudo, K

    1990-11-01

    The feasibility of detecting methamphetamine and its major metabolite, amphetamine, in postmortem tissues over a 2-year period was examined. It is important to determine if the abuse and toxic effects of drugs can be proved from evidence found in decayed, submerged, or stained tissue materials. The blood, urine, liver, skeletal muscle, skin and extremity bones from rabbits given methamphetamine intravenously were kept at room temperature, under 4 different conditions: sealed in a test tube, dried in the open air, submerged in tap water and stained on gauze. Methamphetamine was present in all the samples, with slight change in concentration in case of sealed and air dried tissues. Changes varied in bones kept in water. There were considerable decreases in methamphetamine in blood and urine stains. Despite long term storage, drug abuse and/or toxicity could be determined, in all tissues examined.

  10. Concentrations of trimethoprim and sulphadoxine in tissues from goats and a cow

    International Nuclear Information System (INIS)

    Nielsen, P.; Rasmussen, F.

    1975-01-01

    The concentration of trimethoprim and sulphadoxine in plasma and tissue from goats and a cow have been determined after a single intravenous injection. Furthermore, the concentration of the two drugs and their metabolites in plasma and tissues have been determined after continuous intravenous infusion for 2 1/2 - 3 hrs. Trimethoprim was present in all tissues but brain at higher concentrations than in plasma while the concentration of sulphadoxine in the different tissues were lower than in plasma. The highest concentration of the 2 drugs and their metabolites was found in the kidney. The distribution pattern of trimethoprim and sulphadoxine was similar in cow and goats. (author)

  11. Concentrations of trimethoprim and sulphadoxine in tissues from goats and a cow

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, P; Rasmussen, F [Kongelige Veterinaer- og Landbohoejskole, Copenhagen (Denmark)

    1975-01-01

    The concentration of trimethoprim and sulphadoxine in plasma and tissue from goats and a cow have been determined after a single intravenous injection. Furthermore, the concentration of the two drugs and their metabolites in plasma and tissues have been determined after continuous intravenous infusion for 2 1/2 - 3 hrs. Trimethoprim was present in all tissues but brain at higher concentrations than in plasma while the concentration of sulphadoxine in the different tissues were lower than in plasma. The highest concentration of the 2 drugs and their metabolites was found in the kidney. The distribution pattern of trimethoprim and sulphadoxine was similar in cow and goats.

  12. Concentrations of buparvaquone in milk and tissue of dairy cows.

    Science.gov (United States)

    McDougall, S; Hillerton, J E; Pegram, D

    2016-11-01

    To determine the concentration of the anti-theilerial drug buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of buparvaquone in milk. Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5 mg/kg of one of two formulations of buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018 mg/kg for muscle and 0.00023 mg/L for milk. Concentrations of buparvaquone in milk and tissues were log10-transformed for analysis using multivariate models. In healthy cows, concentrations of buparvaquone in milk declined with time post-treatment (pcows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3). Concentrations of buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows. Detectable concentrations of buparvaquone were found in

  13. Controlled drug release for tissue engineering.

    Science.gov (United States)

    Rambhia, Kunal J; Ma, Peter X

    2015-12-10

    Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Effect of vitamin D3, other drugs altering serum calcium or phosphorus concentrations, and desoxycorticosterone on the distribution of Tc-99m pyrophosphate between target and nontarget tissues

    International Nuclear Information System (INIS)

    Carr, E.A. Jr.; Carroll, M.; Montes, M.

    1981-01-01

    Radioactive imaging agents are chemically designed for selective distribution. Another approach to selectivity is to find stable compounds that favorably influence this distribution. Using a rat model of myocardial necrosis, we studied effects of various stable compounds (as a single, large dose or fractionated into short series) on the ratio, uptake of Tc-99m pyrophosphate (PPi) by the target lesion/uptake by the principal nontarget, bone (L/B). Vitamin D3s ability to increase L/B was mediated by the hypercalcemia and hyperphosphatemia that it caused. The hypercalcemia was accompanied by increased [Ca] in the lesion. In contrast, pulse doses of desoxycorticosterone acetate (DOCA) at 7 and 6 hr before killing increased uptake by lesion, increasing L/B from 0.19 +/- 0.03 to 0.45 +/- 0.08 (p less than 0.01), with no change in serum [Ca] and minimal changes in serum [P], [Na], and [K]. DOCA also increased the lesion-to-blood ratio from 6.5 +/- 0.07 to 15.4 +/- 3.9 (p less than 0.05). These results encourage further study of DOCA's effect and investigation of other stable drugs that may influence distribution of other imaging agents

  15. Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.

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    Oranat Chuchuen

    Full Text Available Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold

  16. Quantitative Analysis of Microbicide Concentrations in Fluids, Gels and Tissues Using Confocal Raman Spectroscopy

    Science.gov (United States)

    Chuchuen, Oranat; Henderson, Marcus H.; Sykes, Craig; Kim, Min Sung; Kashuba, Angela D. M.; Katz, David F.

    2013-01-01

    Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data

  17. Cadmium Concentration in Human Autopsy Tissues.

    Science.gov (United States)

    Lech, Teresa; Sadlik, Józefa K

    2017-10-01

    The concentration of cadmium in human tissues obtained on the basis of autopsies of non-poisoned Polish people (n = 150), aged from 1 to 80 years, examined between 1990 and 2010, is presented. The following values were found in wet digested samples by flame atomic absorption spectrometry (FAAS) (mean ± SD, median, and range, μg/g of wet weight): brain 0.020 ± 0.031, 0.084, 0-0.120 (n = 41); stomach 0.148 ± 0.195, 0.084, 0-1.25 (n = 89); small intestine 0.227 ± 0.231, 0.130, 0-0.830 (n = 39); liver 1.54 ± 1.55, 1.01, 0.015-9.65 (n = 99); kidney 16.0 ± 13.2, 14.0, 0.62-61.3 (n = 91); lung 0.304 ± 0.414, 0.130, 0-1.90 (n = 25); and heart 0.137 ± 0.107, 0.140, 0.017-0.250 (n = 4). Additionally, results (n = 13 people, aged from 2 to 83 years, 63 samples) obtained by inductively coupled plasma optical emission spectrometry (ICP OES) between 2010 and 2015 are given. The obtained data on Cd concentration in the human body can be used to estimate the amounts occurring in "healthy" people and those occurring in cases of chronic or acute poisonings with Cd compounds, which are examined for forensic purposes or to assess environmental exposure levels.

  18. Influence of drug concentration on the diffusion parameters of caffeine

    Science.gov (United States)

    Mustapha, R.Ben; Lafforgue, C.; Fenina, N.; Marty, J.P.

    2011-01-01

    Background and Objectives: In the fields of the pharmaceutical and cosmetic industries and in toxicology, the study of the skin penetration of molecules is very interesting. Various studies have considered the impact of different physicochemical drug characteristics, skin thickness, and formulations, on the transition from the surface of the skin to the underlying tissues or to the systemic circulation; however, the influence of drug concentration on the permeation flux of molecules has rarely been raised. Our study aims to discover the influence of caffeine concentration in a formulation on the percutaneous penetration from gels, as a result of different dose applications to polysulfate membrane and human skin. Materials and Methods: For this purpose, three identical base gels were used at 1, 3, and 5% of caffeine, to evaluate the effect of the concentration of caffeine on in vitro release through the synthetic membrane and ex vivo permeation through the human skin, using diffusion FranzTM cells. Results: The diffusion through the epidermal tissue was significantly slower than through the synthetic membrane, which recorded an increase of flux with an increase in the concentration of caffeine. The skin permeation study showed that diffusion depended not only on the concentration, but also on the deposited amount of gel. Nevertheless, for the same amount of caffeine applied, the flux was more significant from the less concentrated gel. Conclusion: Among all the different concentrations of caffeine examined, 1% gel of caffeine applied at 5 mg / cm2 showed the highest absorption characteristics across human skin. PMID:21572649

  19. Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    Science.gov (United States)

    Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

    2013-07-01

    Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

  20. Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles.

    Science.gov (United States)

    Oh, Jin Sun; Kwon, Yong Seok; Lee, Kyung Ho; Jeong, Woowon; Chung, Sang Kug; Rhee, Kyehan

    2014-01-01

    Drug delivery into neurological tissue is challenging because of the low tissue permeability. Ultrasound incorporating microbubbles has been applied to enhance drug delivery into these tissues, but the effects of a streaming flow by microbubble oscillation on drug perfusion have not been elucidated. In order to clarify the physical effects of steady streaming on drug delivery, an experimental study on dye perfusion into a tissue model was performed using microbubbles excited by acoustic waves. The surface concentration and penetration length of the drug were increased by 12% and 13%, respectively, with streaming flow. The mass of dye perfused into a tissue phantom for 30s was increased by about 20% in the phantom with oscillating bubbles. A computational model that considers fluid structure interaction for streaming flow fields induced by oscillating bubbles was developed, and mass transfer of the drug into the porous tissue model was analyzed. The computed flow fields agreed with the theoretical solutions, and the dye concentration distribution in the tissue agreed well with the experimental data. The computational results showed that steady streaming with a streaming velocity of a few millimeters per second promotes mass transfer into a tissue. © 2013 Published by Elsevier Ltd.

  1. Methadone Recycling Sustains Drug Reservoir in Tissue.

    Science.gov (United States)

    Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie; Schiesser, William E; Boston, Raymond C

    2015-09-01

    We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels. We studied a random sample of six opioid-naïve healthy subjects. We performed a clinical trial simulation in silico using pharmacokinetic modeling. We found a large tissue store of methadone content whose size was much larger than methadone's size in plasma in response to a single oral dose of methadone 10 mg. The tissue store measured 13-17 mg. This finding could only be explained by the contemporaneous storage of methadone in tissue with dose recycling. We found that methadone recycles 2-5 times through an inaccessible extravascular compartment (IAC), from an accessible plasma-containing compartment (AC), before exiting irreversibly. We estimate the rate of accumulation (or storage) of methadone in tissue was 0.029-7.29 mg/h. We predict 39 ± 13% to 83 ± 6% of methadone's tissue stores "spillover" into the circulation. Our results indicate that there exists a large quantifiable tissue store of methadone in humans. Our results support the notion that methadone in humans undergoes tissue uptake, storage, release into the circulation, reuptake from the circulation, and re-release into the circulation, and that spillover of methadone from tissue stores, in part, maintain plasma methadone levels in humans.

  2. Determination of some heavy metals concentration in the tissues of ...

    African Journals Online (AJOL)

    Lead (Pb), Cobalt (Co), and Copper (Cu) concentrations were determined in bone, muscle and gill of two fish species (tilapia fish and cat-fish) collected from Tiga dam Kano, Nigeria during October, 2010. The mean concentrations of the heavy metals varied depending on the type of the tissue and fish species. Generally ...

  3. Polycaprolactone thin films for retinal tissue engineering and drug delivery

    Science.gov (United States)

    Steedman, Mark Rory

    This dissertation focuses on the development of polycaprolactone thin films for retinal tissue engineering and drug delivery. We combined these thin films with techniques such as micro and nanofabrication to develop treatments for age-related macular degeneration (AMD), a disease that leads to the death of rod and cone photoreceptors. Current treatments are only able to slow or limit the progression of the disease, and photoreceptors cannot be regenerated or replaced by the body once lost. The first experiments presented focus on a potential treatment for AMD after photoreceptor death has occurred. We developed a polymer thin film scaffold technology to deliver retinal progenitor cells (RPCs) to the affected area of the eye. Earlier research showed that RPCs destined to become photoreceptors are capable of incorporating into a degenerated retina. In our experiments, we showed that RPC attachment to a micro-welled polycaprolactone (PCL) thin film surface enhanced the differentiation of these cells toward a photoreceptor fate. We then used our PCL thin films to develop a drug delivery device capable of sustained therapeutic release over a multi-month period that would maintain an effective concentration of the drug in the eye and eliminate the need for repeated intraocular injections. We first investigated the biocompatibility of PCL in the rabbit eye. We injected PCL thin films into the anterior chamber or vitreous cavity of rabbit eyes and monitored the animals for up to 6 months. We found that PCL thin films were well tolerated in the rabbit eye, showing no signs of chronic inflammation due to the implant. We then developed a multilayered thin film device containing a microporous membrane. We loaded these devices with lyophilized proteins and quantified drug elution for 10 weeks, finding that both bovine serum albumin and immunoglobulin G elute from these devices with zero order release kinetics. These experiments demonstrate that PCL is an extremely useful

  4. Heavy metals concentration in various tissues of two freshwater ...

    African Journals Online (AJOL)

    Heavy metals like cadmium, zinc, copper, chromium, lead and mercury were measured in the various tissues of Labeo rohita and Channa striatus and in the water samples collected from ... The values of heavy metals concentration in the present study are within the maximum permissible levels for drinking water and fish.

  5. Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs.

    Science.gov (United States)

    Assmus, Frauke; Houston, J Brian; Galetin, Aleksandra

    2017-11-15

    The prediction of tissue-to-plasma water partition coefficients (Kpu) from in vitro and in silico data using the tissue-composition based model (Rodgers & Rowland, J Pharm Sci. 2005, 94(6):1237-48.) is well established. However, distribution of basic drugs, in particular into lysosome-rich lung tissue, tends to be under-predicted by this approach. The aim of this study was to develop an extended mechanistic model for the prediction of Kpu which accounts for lysosomal sequestration and the contribution of different cell types in the tissue of interest. The extended model is based on compound-specific physicochemical properties and tissue composition data to describe drug ionization, distribution into tissue water and drug binding to neutral lipids, neutral phospholipids and acidic phospholipids in tissues, including lysosomes. Physiological data on the types of cells contributing to lung, kidney and liver, their lysosomal content and lysosomal pH were collated from the literature. The predictive power of the extended mechanistic model was evaluated using a dataset of 28 basic drugs (pK a ≥7.8, 17 β-blockers, 11 structurally diverse drugs) for which experimentally determined Kpu data in rat tissue have been reported. Accounting for the lysosomal sequestration in the extended mechanistic model improved the accuracy of Kpu predictions in lung compared to the original Rodgers model (56% drugs within 2-fold or 88% within 3-fold of observed values). Reduction in the extent of Kpu under-prediction was also evident in liver and kidney. However, consideration of lysosomal sequestration increased the occurrence of over-predictions, yielding overall comparable model performances for kidney and liver, with 68% and 54% of Kpu values within 2-fold error, respectively. High lysosomal concentration ratios relative to cytosol (>1000-fold) were predicted for the drugs investigated; the extent differed depending on the lysosomal pH and concentration of acidic phospholipids among

  6. Actinide concentrations in tissues from cattle grazing a contaminated range

    International Nuclear Information System (INIS)

    Smith, D.D.; Bernhardt, D.E.

    1977-01-01

    Actinide concentrations in the tissues of beef animals periodically sacrificed and sampled during a 3-year grazing study on a plutonium-contaminated range of the Nevada Test Site are discussed. Actinide concentrations in the skeletons of the cows originally introduced into the study areas showed little increase with increased time of exposure, while those of animals born in the study areas showed a continued upward trend with time. Plutonium-239/americium-241 ratios in tissues and ingesta suggest little differentiation in the uptake of these radionuclides. However, the plutonium-239/plutonium-238 ratios indicate that plutonium-238 is more readily absorbed. The gonadal concentrations of the actinides were significantly higher than those of blood and muscle and approached those of bone. These data indicate that consideration should be given to the plutonium-239 dose to gonads as well as that to bone, liver, and lungs of man

  7. Using Potentiometric Free Drug Sensors to Determine the Free Concentration of Ionizable Drugs in Colloidal Systems

    DEFF Research Database (Denmark)

    Tran, Thuy; Chakraborty, Anjan; Xi, Xi

    2018-01-01

    The present study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions, emulsions, and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) wer...

  8. Urine Creatinine Concentrations in Drug Monitoring Participants and Hospitalized Patients.

    Science.gov (United States)

    Love, Sara A; Seegmiller, Jesse C; Kloss, Julie; Apple, Fred S

    2016-10-01

    Urine drug testing is commonly performed in both clinical and forensic arenas for screening, monitoring and compliance purposes. We sought to determine if urine creatinine concentrations in monitoring program participants were significantly different from hospital in-patients and out-patients undergoing urine drug testing. We retrospectively reviewed urine creatinine submitted in June through December 2015 for all specimens undergoing urine drug testing. The 20,479 creatinine results were categorized as hospitalized patients (H) and monitoring/compliance groups for pain management (P), legal (L) or recovery (R). Median creatinine concentrations (interquartile range, mg/dL) were significantly different (P creatinine concentrations were significantly lower in the R vs. L group (Pcreatinine concentration and may indicate participants' attempts to tamper with their drug test results through dilution means. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

    Science.gov (United States)

    Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

    2012-01-01

    AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

  10. Evaluation of a Method for Quantifying Eugenol Concentrations in the Fillet Tissue from Freshwater Fish Species.

    Science.gov (United States)

    Meinertz, Jeffery R; Schreier, Theresa M; Porcher, Scott T; Smerud, Justin R

    2016-01-01

    AQUI-S 20E(®) (active ingredient, eugenol; AQUI-S New Zealand Ltd, Lower Hutt, New Zealand) is being pursued for approval as an immediate-release sedative in the United States. A validated method to quantify the primary residue (the marker residue) in fillet tissue from AQUI-S 20E-exposed fish was needed. A method was evaluated for determining concentrations of the AQUI-S 20E marker residue, eugenol, in freshwater fish fillet tissue. Method accuracies from fillet tissue fortified at nominal concentrations of 0.15, 1, and 60 μg/g from six fish species ranged from 88-102%. Within-day and between-day method precisions (% CV) from the fortified tissue were ≤8.4% CV. There were no coextracted compounds from the control fillet tissue of seven fish species that interfered with eugenol analyses. Six compounds used as aquaculture drugs did not interfere with eugenol analyses. The lower limit of quantitation (LLOQ) was 0.012 μg/g. The method was robust, i.e., in most cases, minor changes to the method did not impact method performance. Eugenol was stable in acetonitrile-water (3 + 7, v/v) for at least 14 days, in fillet tissue extracts for 4 days, and in fillet tissue stored at ~ -80°C for at least 84 days.

  11. Alveolar bone tissue engineering using composite scaffolds for drug delivery

    Directory of Open Access Journals (Sweden)

    Tomonori Matsuno

    2010-08-01

    Full Text Available For many years, bone graft substitutes have been used to reconstruct bone defects in orthopedic and dental fields. However, synthetic bone substitutes such as hydroxyapatite or β-tricalcium phosphate have no osteoinductive or osteogenic abilities. Bone tissue engineering has also been promoted as an alternative approach to regenerating bone tissue. To succeed in bone tissue engineering, osteoconductive scaffolding biomaterials should provide a suitable environment for osteogenic cells and provide local controlled release of osteogenic growth factors. In addition, the scaffold for the bone graft substitute should biodegrade to replace the newly formed bone. Recent advances in bone tissue engineering have allowed the creation of composite scaffolds with tailored functional properties. This review focuses on composite scaffolds that consist of synthetic ceramics and natural polymers as drug delivery carriers for alveolar bone tissue engineering.

  12. A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

    Science.gov (United States)

    Poulin, Patrick

    2015-07-01

    A basic assumption in pharmacokinetics-pharmacodynamics research is that the free drug concentration is similar in plasma and tissue, and, hence, in vitro plasma data can be used to estimate the in vivo condition in tissue. However, in a companion manuscript, it has been demonstrated that this assumption is violated for the ionized drugs. Nonetheless, these observations focus on in vitro static environments and do not challenge data with an in vivo dynamic system. Therefore, an extension from an in vitro to an in vivo system becomes the necessary next step. The objective of this study was to perform theoretical simulations of the free drug concentration in tissue and plasma by using a physiologically based pharmacokinetics (PBPK) model reproducing the in vivo conditions in human. Therefore, the effects of drug ionization, lipophilicity, and clearance have been taken into account in a dynamic system. This modeling exercise was performed as a proof of concept to demonstrate that free drug concentration in tissue and plasma may also differ in a dynamic system for passively permeable drugs that are ionized at the physiological pH. The PBPK model simulations indicated that free drug concentrations in tissue cells and plasma significantly differ for the ionized drugs because of the pH gradient effect between cells and interstitial space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD modeling is suggested, which states that the free drug concentration in tissue and plasma will differ for the ionizable drugs in contrast to the neutral drugs. In addition to the pH gradient effect for the ionizable drugs, lipophilicity and clearance effects will increase or decrease the free drug concentration in tissue and plasma for each class of drugs; thus, higher will be the drug lipophilicity and clearance, lower would be the free drug concentration in plasma, and, hence, in tissue, in a dynamic in vivo system. Therefore, only considering the value of free

  13. Concentration of Po-210 and Pb-210 in human tissues

    International Nuclear Information System (INIS)

    Zhao Lancai; Takizawa, Y.; Yamamoto, M.

    1990-01-01

    The levels of Pb-210 and Po-210 in human tissues of people in Japan were determined. Various tissue samples were obtained at autopsy from the cadavers of 22 oncologic cases, mainly in Niigata Prefecture in northern Japan during the period of 1986 to 1988. Wet ashing, followed by electrochemical deposition and alpha-ray spectrometry were used to separate and determine the Pb-210 and Po-210 presented. Among the tissues analyzed the highest concentrations of Pb-210 and Po-210 were observed in bone, liver and kidneys: 1.29, 1.69 and 1.22 Bq.kg -1 respectively for Po-210, and 1.27, 0.56 and 0.43 Bq/kg for Pb-210 respectively. The Po-210/Pb-210 ratios in liver and kidney are 3.0 and 2.9 respectively. Po-210/Pb-210 ratios in other tissues are close to one. The total body burden of Pb-210 and Po-210 was found to be approximately 15.8 Bq and 19.1 Bq respectively

  14. Pericyte-targeting drug delivery and tissue engineering

    Directory of Open Access Journals (Sweden)

    Kang E

    2016-05-01

    Full Text Available Eunah Kang,1 Jong Wook Shin2 1School of Chemical Engineering and Material Science, 2Division of Allergic and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, Chung-Ang University, Dongjak-Gu, Seoul, South Korea Abstract: Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes. Keywords: pericytes, pericyte-targeting drug delivery, tissue engineering, platelet-derived growth factor, angiogenesis, vascular remodeling

  15. Studies on the concentration of antibiotics in tissues, 5

    International Nuclear Information System (INIS)

    Kaneko, Osamu

    1988-01-01

    Incorporation of an antibiotic, Cefotetan (CTT), into the serum and oral cavity following irradiation was pharmacokinetically examined in rats. One shot of 100 mg/kg of CTT was given to the caudal vein at Day 3 to 28 following a single electron beam irradiation of 10 Gy to the mandible. The concentrations of CTT in the serum, tongue, and submandibular gland were serially determined using high performance liquid chromatography 5 to 60 min after injection. The minimum biological half-life of CTT in the serum was attained at Day 14 postirradiation. The concentrations of CTT in tissues increased and biological half-life prolonged up to Day 14 postirradiation. These values tended to return to the control values up to Day 28. There was serial correlation between a decrease in serum protein mass up to Day 21 and biological half-life of serum CTT. (N.K.)

  16. Electrospun nanofibrous materials for tissue engineering and drug delivery

    Directory of Open Access Journals (Sweden)

    Wenguo Cui, Yue Zhou and Jiang Chang

    2010-01-01

    Full Text Available The electrospinning technique, which was invented about 100 years ago, has attracted more attention in recent years due to its possible biomedical applications. Electrospun fibers with high surface area to volume ratio and structures mimicking extracellular matrix (ECM have shown great potential in tissue engineering and drug delivery. In order to develop electrospun fibers for these applications, different biocompatible materials have been used to fabricate fibers with different structures and morphologies, such as single fibers with different composition and structures (blending and core-shell composite fibers and fiber assemblies (fiber bundles, membranes and scaffolds. This review summarizes the electrospinning techniques which control the composition and structures of the nanofibrous materials. It also outlines possible applications of these fibrous materials in skin, blood vessels, nervous system and bone tissue engineering, as well as in drug delivery.

  17. The Concentration of Nutrients in Tissues of Plantation-Grown Eastern Cottonwood (Populus deltoides Bart.)

    Science.gov (United States)

    M. G. Shelton; L. E. Nelson; G. L. Switzer; B. G. Blackmon

    1981-01-01

    Nutrient concentrations were determined for 10 tissues from each of 24 cottonwood trees that ranged in age from four to 16 years. Highest concentrations occurred in the most physiologically active tissues; i.e., stemtips, current branches and foliage. Tree age had little influence on the variation in nutrient concentration of tissues. Some differences in concentrations...

  18. Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

    Directory of Open Access Journals (Sweden)

    Hiroaki Todo

    2013-12-01

    Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

  19. Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

    Science.gov (United States)

    Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

    2009-04-01

    Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

  20. Interspecies comparison of the tissue distribution of WR-2721, a radioprotective drug

    International Nuclear Information System (INIS)

    Washburn, L.C.; Rafter, J.J.; Hayes, R.L.; Yuhas, J.M.

    1975-01-01

    Pre-irradiation intravenous administration of the radioprotective drug S-2-[3-aminopropylamino]ethylphosphorothioic acid (WR-2721) has potential value in radiotherapy because it doubles the radiation resistance of normal mouse tissues while affording only minimal protection to tumors. Deficient deposition of WR- 2721 in tumor tissue has recently been demonstrated and this is thought to be a major reason for the preferential protection of normal tissues by the drug. Data originally obtained in studies using the mouse and rat indicated that the tissue distribution of WR-2721 was possibly more closely related to dose per unit surface area than to dose per unit weight. To test this hypothesis an interspecies comparison of the tissue distribution of 35 S-labeled WR-2721 was carried out in normal mice, rats, rabbits, and dogs at 15 and 30 minutes after intravenous administration. Results suggest that the surface area and body weight exert equal effects on the tissue concentration of WR-2721. The results further suggest that lower absolute doses of WR-2721 in the human, possibly as low as 20 mg/kg, may provide a radioprotective effect equivalent to that produced from 100 mg/kg in the mouse, i.e., a 50 to 80 percent increase in radiation resistance (CH)

  1. Trends in drug delivery through tissue barriers containing tight junctions.

    Science.gov (United States)

    Tscheik, Christian; Blasig, Ingolf E; Winkler, Lars

    2013-04-01

    A limitation in the uptake of many drugs is the restricted permeation through tissue barriers. There are two general ways to cross barriers formed by cell layers: by transcytosis or by diffusion through the intercellular space. In the latter, tight junctions (TJs) play the decisive role in the regulation of the barrier permeability. Thus, transient modulation of TJs is a potent strategy to improve drug delivery. There have been extensive studies on surfactant-like absorption enhancers. One of the most effective enhancers found is sodium caprate. However, this modulates TJs in an unspecific fashion. A novel approach would be the specific modulation of TJ-associated marvel proteins and claudins, which are the main structural components of the TJs. Recent studies have identified synthetic peptidomimetics and RNA interference techniques to downregulate the expression of targeted TJ proteins. This review summarizes current progress and discusses the impact on TJs' barrier function.

  2. Serum magnesium concentration in drug-addicted patients.

    Science.gov (United States)

    Karakiewicz, Beata; Kozielec, Tadeusz; Brodowski, Jacek; Chlubek, Dariusz; Noceń, Iwona; Starczewski, Andrzej; Brodowska, Agnieszka; Laszczyńska, Maria

    2007-03-01

    Drug addiction is a complex problem which leads to many somatic, psychic and social diseases. It is accompanied by the disturbed metabolism of various macro and micronutrients. The aim of this study was to assess serum magnesium concentration in drug-addicted patients and analyze whether Human Immunodeficiency Virus (HIV) infection and methadone treatment affect the level of serum magnesium in these patients. The examination was conducted in a group of 83 people - patients of Szczecin-Zdroje Psychiatric Hospital (Poland). They were 21 to 49 years old, and the mean age was 32 +/- 7 years. The control group consisted of 81 healthy individuals. Flame atomic-absorption spectrometry method was used to determine the magnesium concentration. The total serum magnesium concentration was calculated for the whole patient group, subgroups of women and men, a subgroup of people infected with HIV, and a subgroup receiving methadone substitution treatment. How magnesium behaves depending on age and addiction period, was checked. The mean concentration of magnesium in blood serum of the patients examined was 0.57 mmol/L, which was significantly lower than in the control group. In the subgroup of men it was 0.57 mmol/L, and in the subgroup of women - 0.55 mmol/L; the differences were not statistically significant. In the patient group nobody had the appropriate magnesium concentration in blood serum. No significant correlation was found between the magnesium concentration, age of the patients and addiction period. In the subgroup of seropositive people the mean concentration of magnesium was 0.55 mmol/L, and in the subgroup of non-infected patients - 0.58 mmol/L; the difference was not statistically significant. The mean concentration of magnesium in the subgroup treated with methadone was 0.59 mmol/L, and in the subgroup not involved in this type of therapy - 0.55 mmol/L; it was not a statistically significant difference.

  3. Pharmacokinetics and Efficacy of Topically Applied Nonsteroidal Anti-Inflammatory Drugs in Retinochoroidal Tissues in Rabbits

    Science.gov (United States)

    Kida, Tetsuo; Kozai, Seiko; Takahashi, Hiroaki; Isaka, Mitsuyoshi; Tokushige, Hideki; Sakamoto, Taiji

    2014-01-01

    Purpose To evaluate the pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs (NSAIDs) in the retinochoroidal tissues of rabbits. Methods The cyclooxygenase (COX) inhibitory activity of diclofenac, bromfenac, and amfenac, an active metabolite of nepafenac, were determined using human-derived COX-1 and COX-2. Each of the three NSAIDs was applied topically to rabbits, and after 0.5 to 8 hrs, the concentration of each drug in the aqueous humor and the retinochoroidal tissues was measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetics of the drugs in the tissues after repeated doses as is done on patients was calculated by a simulation software. The inhibitory effect of each NSAID on the breakdown of the blood-retinal barrier was assessed by the vitreous protein concentration on concanavalin A-induced retinochoroidal inflammation in rabbits. Results The half-maximal inhibitory concentration (IC50) of diclofenac, bromfenac, and amfenac was 55.5, 5.56, and 15.3 nM for human COX-1, and 30.7, 7.45, and 20.4 nM for human COX-2, respectively. The three NSAIDs were detected in the aqueous humor and the retinochoroidal tissue at all-time points. Simulated pharmacokinetics showed that the levels of the three NSAIDs were continuously higher than the IC50 of COX-2, as an index of efficacy, in the aqueous humor, whereas only the bromfenac concentration was continuously higher than the IC50 at its trough level in the retinochoroidal tissues. The intravitreous concentration of proteins was significantly reduced in rabbits that received topical bromfenac (P = 0.026) but not the other two NSAIDs. Conclusions Topical bromfenac can penetrate into the retinochoroidal tissues in high enough concentrations to inhibit COX-2 and exerts its inhibitory effect on the blood-retinal barrier breakdown in an experimental retinochoroidal inflammation in rabbits. Topical bromfenac may have a better therapeutic benefit than diclofenac and

  4. Pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs in retinochoroidal tissues in rabbits.

    Directory of Open Access Journals (Sweden)

    Tetsuo Kida

    Full Text Available PURPOSE: To evaluate the pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs (NSAIDs in the retinochoroidal tissues of rabbits. METHODS: The cyclooxygenase (COX inhibitory activity of diclofenac, bromfenac, and amfenac, an active metabolite of nepafenac, were determined using human-derived COX-1 and COX-2. Each of the three NSAIDs was applied topically to rabbits, and after 0.5 to 8 hrs, the concentration of each drug in the aqueous humor and the retinochoroidal tissues was measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetics of the drugs in the tissues after repeated doses as is done on patients was calculated by a simulation software. The inhibitory effect of each NSAID on the breakdown of the blood-retinal barrier was assessed by the vitreous protein concentration on concanavalin A-induced retinochoroidal inflammation in rabbits. RESULTS: The half-maximal inhibitory concentration (IC50 of diclofenac, bromfenac, and amfenac was 55.5, 5.56, and 15.3 nM for human COX-1, and 30.7, 7.45, and 20.4 nM for human COX-2, respectively. The three NSAIDs were detected in the aqueous humor and the retinochoroidal tissue at all-time points. Simulated pharmacokinetics showed that the levels of the three NSAIDs were continuously higher than the IC50 of COX-2, as an index of efficacy, in the aqueous humor, whereas only the bromfenac concentration was continuously higher than the IC50 at its trough level in the retinochoroidal tissues. The intravitreous concentration of proteins was significantly reduced in rabbits that received topical bromfenac (P = 0.026 but not the other two NSAIDs. CONCLUSIONS: Topical bromfenac can penetrate into the retinochoroidal tissues in high enough concentrations to inhibit COX-2 and exerts its inhibitory effect on the blood-retinal barrier breakdown in an experimental retinochoroidal inflammation in rabbits. Topical bromfenac may have a better therapeutic benefit

  5. Preliminary study of tissue concentrations of penicillin after local administration into the guttural pouches in four healthy horses.

    Science.gov (United States)

    Kendall, A; Mayhew, I G; Petrovski, K

    2016-08-01

    Treatment of subclinical carriers of Streptococcus equi subsp. equi with a gelatine-penicillin formulation deposited in the guttural pouch has been empirically proposed, but data on local tissue penicillin concentrations after treatment are lacking. We analysed tissue levels of penicillin after administration into the guttural pouches of four healthy horses. Two horses received local treatment with gelatine-penicillin and two horses received local treatment with an intramammary formulation of penicillin. Tissues were harvested for analysis either 12 or 24 h later. Results indicate that local treatment may be effective, but more research on optimal drug formulations in a larger sample size is warranted. © 2016 Australian Veterinary Association.

  6. Thermal damage control of dye-assisted laser tissue welding: effect of dye concentration

    Science.gov (United States)

    Xie, Hua; Buckley, Lisa A.; Prahl, Scott A.; Shaffer, Brian S.; Gregory, Kenton W.

    2001-05-01

    Successful laser-assisted tissue welding was implemented to provide proper weld strength with minimized tissue thermal injury. We investigated and compared the weld strengths and morphologic changes in porcine small intestinal submucose (SIS) and porcine ureteral tissues with various concentration of indocyanine green (ICG) and with a solid albumin sheet. The study showed that the tissues were welded at lower ICG concentration (0.05 mM) with minimized tissue thermal damage using an 800-nm wavelength diode laser.

  7. Core-shell designed scaffolds for drug delivery and tissue engineering.

    Science.gov (United States)

    Perez, Roman A; Kim, Hae-Won

    2015-07-01

    Scaffolds that secure and deliver therapeutic ingredients like signaling molecules and stem cells hold great promise for drug delivery and tissue engineering. Employing a core-shell design for scaffolds provides a promising solution. Some unique methods, such as co-concentric nozzle extrusion, microfluidics generation, and chemical confinement reactions, have been successful in producing core-shelled nano/microfibers and nano/microspheres. Signaling molecules and drugs, spatially allocated to the core and/or shell part, can be delivered in a controllable and sequential manner for optimal therapeutic effects. Stem cells can be loaded within the core part on-demand, safely protected from the environments, which ultimately affords ex vivo culture and in vivo tissue engineering. The encapsulated cells experience three-dimensional tissue-mimic microenvironments in which therapeutic molecules are secreted to the surrounding tissues through the semi-permeable shell. Tuning the material properties of the core and shell, changing the geometrical parameters, and shaping them into proper forms significantly influence the release behaviors of biomolecules and the fate of the cells. This topical issue highlights the immense usefulness of core-shell designs for the therapeutic actions of scaffolds in the delivery of signaling molecules and stem cells for tissue regeneration and disease treatment. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Effect of cooking on radionuclide concentrations in waterfowl tissues

    International Nuclear Information System (INIS)

    Halford, D.K.

    1983-01-01

    Twenty-four commercially raised mallar ducks (Anas platyrhyncos) were released at the Test Reactor Area radioactive leaching ponds, and subsequently collected 56 to 188 days later. Liver, gizzard, and carcass were analyzed for radionuclide concentrations before and after cooking. Significant decreases (P 137 Cs, 134 Cs, 60 Co, 140 La and /sup 110m/Ag concentrations in carcass and liver samples occurred after cooking. Radionuclide concentrations in gizzard showed no significant change in radionuclide concentrations after cooking. Cesium-134 and 137 Cs concentrations decreased by 27% in carcass after cooking and reduced the dose commitment to man by that amount

  9. Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

    Science.gov (United States)

    Kevadiya, Bhavesh D.; Woldstad, Christopher; Ottemann, Brendan M.; Dash, Prasanta; Sajja, Balasrinivasa R.; Lamberty, Benjamin; Morsey, Brenda; Kocher, Ted; Dutta, Rinku; Bade, Aditya N.; Liu, Yutong; Callen, Shannon E.; Fox, Howard S.; Byrareddy, Siddappa N.; McMillan, JoEllyn M.; Bronich, Tatiana K.; Edagwa, Benson J.; Boska, Michael D.; Gendelman, Howard E.

    2018-01-01

    RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models. METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution. RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate. CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy. PMID:29290806

  10. Eyelid skin as a potential site for drug delivery to conjunctiva and ocular tissues.

    Science.gov (United States)

    See, Gerard Lee; Sagesaka, Ayano; Sugasawa, Satoko; Todo, Hiroaki; Sugibayashi, Kenji

    2017-11-25

    The feasibility of topical application onto the (lower) eyelid skin to deliver hydrophilic and lipophilic compounds into the conjunctiva and ocular tissues was evaluated by comparing with conventional eye drop application. Skin permeation and the concentration of several model compounds, and skin impedance were determined utilizing eyelid skin from hairless rats, as well as abdominal skin in the same animals for comparison. In vitro static diffusion cells were used to assess the skin permeation in order to provide key insights into the relationship between the skin sites and drugs. The obtained results revealed that drug permeation through the eyelid skin was much higher than that through abdominal skin regardless of the drug lipophilicity. Specifically, diclofenac sodium salt and tranilast exhibited approximately 6-fold and 11-fold higher permeability coefficients, respectively, through eyelid skin compared with abdominal skin. Histomorphological evaluation and in vivo distribution of model fluorescent dyes were also examined in the conjunctiva and skin after eyelid administration by conventional microscope and confocal laser scanning microscope analyses. The result revealed that eyelid skin has a thinner stratum corneum, thereby showing lower impedance, which could be the reason for the higher drug permeation through eyelid skin. Comparative evaluation of lipophilic and hydrophilic model compounds administered via the eyelid skin over 8h revealed stronger fluorescence intensity in the skin and surrounding tissues compared with eye drop administration. These results suggested that the (lower) eyelid skin is valuable as a prospective site for ophthalmic medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Metal concentrations in selected organs and tissues of five Red ...

    African Journals Online (AJOL)

    The absence of metalprocessing industries in the catchments of the Florida Lake and the Steynsrus farm dams reflects the low liver and kidney concentrations of Cd, Ni and Cu, respectively. The blood of the Natalspruit wetland coots contained the highest dry weight concentrations of Ni (11.4 mg/g), Cd (1.8 mg/g) and Cu ...

  12. Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

    Science.gov (United States)

    Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan

    2018-02-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

  13. Determination of some heavy metals concentration in the tissues of ...

    African Journals Online (AJOL)

    Jen

    Department of Pure and Industrial Chemistry, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria ... contamination (e.g. lead pipes), high ambient air concentrations near emission ... Thus heavy metals acquired through the food chain as a.

  14. Mercury concentrations in multiple tissues of Kittlitz's murrelets (Brachyramphus brevirostris)

    Science.gov (United States)

    Kenney, Leah A.; Kaler, Robb S.; Kissling, Michelle L.; Bond, Alexander L.; Eagles-Smith, Collin A.

    2018-01-01

    Mercury (Hg) is a non-essential, toxic metal that is distributed worldwide. Mercury biomagnifies in food webs and can threaten the health of top predators such as seabirds. The Kittlitz's murrelet (Brachyramphus brevirostris) is a seabird endemic to Alaska and the Russian Far East and is a species of conservation concern in the region. We determined Hg concentrations in eggshells, guano, blood, and feathers of Kittlitz's murrelets sampled from four locations in Alaska. Mercury concentrations in eggshells, guano, and blood were low compared to other seabird species. Mean Hg concentrations of breast feathers from Adak Island and Glacier Bay were significantly greater than those from Agattu Island or Icy Bay. Two Kittlitz's murrelets at Glacier Bay and one Kittlitz's murrelet at Adak Island had Hg concentrations above those associated with impaired reproduction in other bird species, and may merit further investigation as a potential threat to individuals and populations.

  15. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover.

    Science.gov (United States)

    Jugdaohsingh, Ravin; Watson, Abigail I E; Pedro, Liliana D; Powell, Jonathan J

    2015-06-01

    Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than

  16. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover☆

    Science.gov (United States)

    Jugdaohsingh, Ravin; Watson, Abigail I.E.; Pedro, Liliana D.; Powell, Jonathan J.

    2015-01-01

    Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague–Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n = 8–10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2–6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague–Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially

  17. Ray tissues as an indirect measure of relative sap-sugar concentration in sugar maple

    Science.gov (United States)

    Peter W. Garrett; Kenneth R. Dudzik; Kenneth R. Dudzik

    1989-01-01

    Attempts to correlate ray tissue as a percentage of total wood volume with sap-sugar concentrations of sugar maple progenies were unsuccessful. These results raise doubts about our ability to use a relatively constant value such as ray-tissue volume in a selection program designed to increase the sap-sugar concentration of sugar maple seedlings.

  18. Comparison of metal concentrations in rat tibia tissues with various metallic implants.

    Science.gov (United States)

    Okazaki, Yoshimitsu; Gotoh, Emiko; Manabe, Takeshi; Kobayashi, Kihei

    2004-12-01

    To compare metal concentrations in tibia tissues with various metallic implants, SUS316L stainless steel, Co-Cr-Mo casting alloy, and Ti-6Al-4V and V-free Ti-15Zr-4Nb-4Ta alloys were implanted into the rat tibia for up to 48 weeks. After the implant was removed from the tibia by decalcification, the tibia tissues near the implant were lyophilized. Then the concentrations of metals in the tibia tissues by microwave acid digestion were determined by inductively coupled plasma-mass spectrometry. Fe concentrations were determined by graphite-furnace atomic absorption spectrometry. The Fe concentration in the tibia tissues with the SUS316L implant was relatively high, and it rapidly increased up to 12 weeks and then decreased thereafter. On the other hand, the Co concentration in the tibia tissues with the Co-Cr-Mo implant was lower, and it increased up to 24 weeks and slightly decreased at 48 weeks. The Ni concentration in the tibia tissues with the SUS316L implant increased up to 6 weeks and then gradually decreased thereafter. The Cr concentration tended to be higher than the Co concentration. This Cr concentration linearly increased up to 12 weeks and then decreased toward 48 weeks in the tibia tissues with the SUS316L or Co-Cr-Mo implant. Minute quantities of Ti, Al and V in the tibia tissues with the Ti-6Al-4V implant were found. The Ti concentration in the tibia tissues with the Ti-15Zr-4Nb-4Ta implant was lower than that in the tibia tissues with the Ti-6Al-4V implant. The Zr, Nb and Ta concentrations were also very low. The Ti-15Zr-4Nb-4Ta alloy with its low metal release in vivo is considered advantageous for long-term implants.

  19. Drug-Loadable Calcium Alginate Hydrogel System for Use in Oral Bone Tissue Repair.

    Science.gov (United States)

    Chen, Luyuan; Shen, Renze; Komasa, Satoshi; Xue, Yanxiang; Jin, Bingyu; Hou, Yepo; Okazaki, Joji; Gao, Jie

    2017-05-06

    This study developed a drug-loadable hydrogel system with high plasticity and favorable biological properties to enhance oral bone tissue regeneration. Hydrogels of different calcium alginate concentrations were prepared. Their swelling ratio, degradation time, and bovine serum albumin (BSA) release rate were measured. Human periodontal ligament cells (hPDLCs) and bone marrow stromal cells (BMSCs) were cultured with both calcium alginate hydrogels and polylactic acid (PLA), and then we examined the proliferation of cells. Inflammatory-related factor gene expressions of hPDLCs and osteogenesis-related gene expressions of BMSCs were observed. Materials were implanted into the subcutaneous tissue of rabbits to determine the biosecurity properties of the materials. The materials were also implanted in mandibular bone defects and then scanned using micro-CT. The calcium alginate hydrogels caused less inflammation than the PLA. The number of mineralized nodules and the expression of osteoblast-related genes were significantly higher in the hydrogel group compared with the control group. When the materials were implanted in subcutaneous tissue, materials showed favorable biocompatibility. The calcium alginate hydrogels had superior osteoinductive bone ability to the PLA. The drug-loadable calcium alginate hydrogel system is a potential bone defect reparation material for clinical dental application.

  20. Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density.

    Science.gov (United States)

    Johnson, E J; Hammond, B R; Yeum, K J; Qin, J; Wang, X D; Castaneda, C; Snodderly, D M; Russell, R M

    2000-06-01

    Lutein and zeaxanthin are the only carotenoids in the macular region of the retina (referred to as macular pigment [MP]). Foods that are rich in lutein and zeaxanthin can increase MP density. Response to dietary lutein and zeaxanthin in other tissues has not been studied. The objective of this study was to examine tissue responses to dietary lutein and zeaxanthin and relations among tissues in lutein and zeaxanthin concentrations. Seven subjects consumed spinach and corn, which contain lutein and zeaxanthin, with their daily diets for 15 wk. At 0, 4, 8, and 15 wk and 2 mo after the study, serum, buccal mucosa cells, and adipose tissue were analyzed for carotenoids, and MP density was measured. Serum and buccal cell concentrations of lutein increased significantly from baseline during dietary modification. Serum zeaxanthin concentrations were greater than at baseline only at 4 wk, whereas buccal cell and adipose tissue concentrations of zeaxanthin did not change. Adipose tissue lutein concentrations peaked at 8 wk. Changes in adipose tissue lutein concentration were inversely related to the changes in MP density, suggesting an interaction between adipose tissue and retina in lutein metabolism. To investigate the possibility of tissue interactions, we examined cross-sectional relations among serum, tissue, and dietary lutein concentrations, anthropometric measures, and MP density in healthy adults. Significant negative correlations were found between adipose tissue lutein concentrations and MP for women, but a significant positive relation was found for men. Sex differences in lutein metabolism may be an important factor in tissue interactions and in determining MP density.

  1. Tissue heavy metal concentrations of stranded California sea lions (Zalophus californianus) in Southern California

    Energy Technology Data Exchange (ETDEWEB)

    Harper, Erin R. [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States)]. E-mail: erin-harper@hotmail.com; St Leger, Judy A. [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Westberg, Jody A. [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Mazzaro, Lisa [Mystic Aquarium and Institute for Exploration, 55 Coogan Blvd, Mystic, CT 06355 (United States); Schmitt, Todd [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Reidarson, Tom H. [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Tucker, Melinda [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Cross, Dee H. [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Puschner, Birgit [California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616 (United States)

    2007-06-15

    Concentrations of nine heavy metals (As, Cd, Cu, Fe, Hg, Pb, Mn, Mo and Zn) were determined in the hepatic and renal tissues of 80 stranded California sea lions (Zalophus californianus). Significant age-dependant increases were observed in liver and kidney concentrations of cadmium and mercury, and renal zinc concentrations. Hepatic iron concentrations were significantly higher in females than males. Animals with suspected domoic acid associated pathological findings had significantly higher concentrations of liver and kidney cadmium; and significantly higher liver mercury concentrations when compared to animals classified with infectious disease or traumatic mortality. Significantly higher hepatic burdens of molybdenum and zinc were found in animals that died from infectious diseases. This is the largest study of tissue heavy metal concentrations in California sea lions to date. These data demonstrate how passive monitoring of stranded animals can provide insight into environmental impacts on marine mammals. - Tissue heavy metal concentrations are valuable in population and environmental monitoring.

  2. Concentration of uranium in human cancerous tissues of Southern Iraqi patients using fission track analysis

    International Nuclear Information System (INIS)

    Al-Hamzawi, A.A.; Al-Qadisiyah University, Qadisiyah; Jaafar, M.S.; Tawfiq, N.F.

    2015-01-01

    The technique of nuclear fission track analysis with solid state nuclear track detectors CR-39 has been applied to determine concentrations of uranium in cancerous samples of human tissues that excised from patients in the three key southern Iraqi governorates namely, Basrah, Dhi-Qar, and Muthanna. These provinces were the sites of intensive military events during the Gulf Wars in 1991 and 2003. The investigation was based on the study of 24 abnormal samples and 12 normal samples for comparing the results. These samples include four types of soft tissues (kidney, breast, stomach and uterus). The results show that uranium concentrations in the normal tissues ranged between (1.42-4.76 μg kg -1 ), whereas in the cancerous tissues ranged between (3.37-7.22 μg kg -1 ). The uranium concentrations in the normal tissues were significantly lower than in the abnormal tissues (P < 0.001). (author)

  3. Non-invasive measurement and imaging of tissue iron oxide nanoparticle concentrations in vivo using proton relaxometry

    International Nuclear Information System (INIS)

    St Pierre, T G; Clark, P R; Chua-anusorn, W; Fleming, A; Pardoe, H; Jeffrey, G P; Olynyk, J K; Pootrakul, P; Jones, S; Moroz, P

    2005-01-01

    Magnetic nanoparticles and microparticles can be found in biological tissues for a variety of reasons including pathological deposition of biogenic particles, administration of synthetic particles for scientific or clinical reasons, and the inclusion of biogenic magnetic particles for the sensing of the geomagnetic field. In applied magnetic fields, the magnetisation of tissue protons can be manipulated with radiofrequency radiation such that the macroscopic magnetisation of the protons precesses freely in the plane perpendicular to the applied static field. The presence of magnetic particles within tissue enhances the rate of dephasing of proton precession with higher concentrations of particles resulting in higher dephasing rates. Magnetic resonance imaging instruments can be used to measure and image the rate of decay of spin echo recoverable proton transverse magnetisation (R 2 ) within tissues enabling the measurement and imaging of magnetic particle concentrations with the aid of suitable calibration curves. Applications include the non-invasive measurement of liver iron concentrations in iron-overload disorders and measurement and imaging of magnetic particle concentrations used in magnetic hyperthermia therapy. Future applications may include the tracking of magnetically labelled drugs or biomolecules and the measurement of fibrotic liver damage

  4. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

    NARCIS (Netherlands)

    Brockow, K.; Garvey, L. H.; Aberer, W.; Atanaskovic-Markovic, M.; Barbaud, A.; Bilo, M. B.; Bircher, A.; Blanca, M.; Bonadonna, B.; Campi, P.; Castro, E.; Cernadas, J. R.; Chiriac, A. M.; Demoly, P.; Grosber, M.; Gooi, J.; Lombardo, C.; Mertes, P. M.; Mosbech, H.; Nasser, S.; Pagani, M.; Ring, J.; Romano, A.; Scherer, K.; Schnyder, B.; Testi, S.; Torres, M.; Trautmann, A.; Terreehorst, I.

    2013-01-01

    Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable

  5. Concentration of 232Th, 230Th and 228Th in various tissues of Japanese subjects

    International Nuclear Information System (INIS)

    Takizawa, Y.; Qingmei, H.; Hisamatsu, S.; Abe, T.

    1997-01-01

    The concentration of 232 Th, 230 Th and 228 Th in various human tissues of Japanese subjects obtained at autopsies are reported. The tissue samples were weighed, spiked with 234 Th tracer and ashed by acid. The solution was dried on a hot-plate. Separation of thorium radionuclides was accomplished through cation-exchange resin chromatography and electrodeposition. The concentrations of thorium isotopes were measured by α-spectrometry. Thorium-232 and 230 Th concentrations were found to be highest in lung, followed by bone. The maximum concentration of 228 Th was in bone. The lowest concentrations of thorium isotopes were in muscle. (author)

  6. Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations.

    Science.gov (United States)

    Newton, Adam J H; Wall, Mark J; Richardson, Magnus J E

    2017-03-01

    Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and glutamate. A great deal of experimental and modeling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modeling and experimentally verify our predictions in diffusive environments. NEW & NOTEWORTHY Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue

  7. Controlled delivery of antiangiogenic drug to human eye tissue using a MEMS device

    KAUST Repository

    Pirmoradi, Fatemeh Nazly; Ou, Kevin; Jackson, John K.; Letchford, Kevin; Cui, Jing; Wolf, Ki Tae; Graber, Florian; Zhao, Tom; Matsubara, Joanne A.; Burt, Helen; Chiao, Mu; Lin, Liwei

    2013-01-01

    We demonstrate an implantable MEMS drug delivery device to conduct controlled and on-demand, ex vivo drug transport to human eye tissue. Remotely operated drug delivery to human post-mortem eyes was performed via a MEMS device. The developed curved

  8. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

    DEFF Research Database (Denmark)

    Brockow, K; Garvey, L H; Aberer, W

    2013-01-01

    Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable...... indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature...... search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group...

  9. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    Science.gov (United States)

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. Excipient-drug pharmacokinetic interactions: Effect of disintegrants on efflux across excised pig intestinal tissues

    Directory of Open Access Journals (Sweden)

    Werner Gerber

    2018-04-01

    Full Text Available Pharmaceutical excipients were designed originally to be pharmacologically inert. However, certain excipients were found to have altering effects on drug pharmacodynamics and/or pharmacokinetics. Pharmacokinetic interactions may be caused by modulation of efflux transporter proteins, intercellular tight junctions and/or metabolic enzyme amongst others. In this study, five disintegrants from different chemical classes were evaluated for P-glycoprotein (P-gp related inhibition and tight junction modulation effects. Bi-directional transport studies of the model compound, Rhodamine 123 (R123 were conducted in the absence (control group and presence (experimental groups of four concentrations of each selected disintegrant across excised pig jejunum tissue. The results showed that some of the selected disintegrants (e.g. Ac-di-sol® and Kollidon® CL-M increased R123 absorptive transport due to inhibition of P-gp related efflux, while another disintegrant (e.g. sodium alginate changed R123 transport due to inhibition of P-gp in conjunction with a transient opening of the tight junctions in a concentration dependent way. It may be concluded that the co-application of some disintegrants to the intestinal epithelium may lead to pharmacokinetic interactions with drugs that are susceptible to P-gp related efflux. However, the clinical significance of these in vitro permeation findings should be confirmed by means of in vivo studies. Keywords: Disintegrants, Excipient, Ex vivo, P-glycoprotein, Pharmacokinetic interactions, Rhodamine 123

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

    Science.gov (United States)

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

    2013-01-01

    Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

  12. Mitoxantrone Loaded Superparamagnetic Nanoparticles for Drug Targeting: A Versatile and Sensitive Method for Quantification of Drug Enrichment in Rabbit Tissues Using HPLC-UV

    Directory of Open Access Journals (Sweden)

    Rainer Tietze

    2010-01-01

    Full Text Available In medicine, superparamagnetic nanoparticles bound to chemotherapeutics are currently investigated for their feasibility in local tumor therapy. After intraarterial application, these particles can be accumulated in the targeted area by an external magnetic field to increase the drug concentration in the region of interest (Magnetic-Drug-Targeting. We here present an analytical method (HPLC-UV, to detect pure or ferrofluid-bound mitoxantrone in a complex matrix even in trace amounts in order to perform biodistribution studies. Mitoxantrone could be extracted in high yields from different tissues. Recovery of mitoxantrone in liver tissue (5000 ng/g was 76±2%. The limit of quantification of mitoxantrone standard was 10 ng/mL ±12%. Validation criteria such as linearity, precision, and stability were evaluated in ranges achieving the FDA requirements. As shown for pilot samples, biodistribution studies can easily be performed after application of pure or ferrofluid-bound mitoxantrone.

  13. Prompt gamma-ray spectrometry for measurement of B-10 concentration in brain tissue and blood

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Kitamura, Katsuji; Kobayashi, Toru; Matsumoto, Keizo; Hatanaka, Hiroshi.

    1993-01-01

    Boron-10 (B-10) concentration in the brain tissue and blood was measured continuously for 24 hours after injection of the B-10 compound in live rabbits using prompt gamma-ray spectrometry. Following injection of B-10 compound (Na 2 B 12 H 11 SH, 50mg/kg) dissolved in physiological saline, B-10 concentration was continuously measured in the brain tissue. Intermittently the concentration of B-10 in blood and cerebro-spinal fluid (CSF) was also measured. In 10 minutes after the injection of B-10 compound, the level of B-10 concentration reached the peak of 400-500 ppm in blood and 20-30 ppm in the normal brain tissue. In 60 minutes the level of B-10 concentration rapidly decreased and then a gradual decline was observed. The value was 15-30 ppm at 3 hours after injection, 5-10 ppm at 6 hours and 2-5 ppm at 24 hours in the blood. The concentration in the brain tissue was 3-8 ppm at 3 hours, 2-5 ppm at 6 hours and below 1.5 ppm at 24 hours. B-10 concentration in cerebro-spinal fluid was below 1 ppm. B-10 concentration was also measured in the brain tumor and blood in the human cases at boron neutron capture therapy (BNCT). These data studied by prompt gamma-ray spectrometry are very important and useful to decide the irradiation time. (author)

  14. Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses.

    Science.gov (United States)

    Morris, Aaron H; Mahal, Rajwant S; Udell, Jillian; Wu, Michelle; Kyriakides, Themis R

    2017-10-01

    Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor-κB (NF-κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor-β (TGF-β)-induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose-dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Concentration of mercury and selenium in tissues of five cetacean species from Croatian coastal waters

    Directory of Open Access Journals (Sweden)

    Bilandžić Nina

    2015-01-01

    Full Text Available Mercury (Hg and selenium (Se concentrations were measured in muscle, liver, kidney, spleen and lung tissues of five cetacean species, three dolphin (Stenella coeruleoalba, Tursiops truncatus and Grampus griseus and two whale species (Balaenoptera physalus and Ziphius cavirostris, stranded along the Croatian coast during the period 1999-2002. Statistically significant differences in Hg concentrations in muscle, spleen and lung, and Se in liver and lung of the different dolphin species were observed. Mercury levels in liver and spleen and Se levels in liver differed between young and adult T. truncatus species. A significant positive correlation between different tissue types for Hg and Se concentrations was observed. In all tissues tested, the lowest Hg and Se concentrations were found in B. physalus. Mercury concentrations were positively correlated with Se in all tissues. The results present one of few studies related to lung and spleen tissues in these mammals, particularly in the Adriatic Sea. Since very little data are available, this research provides new data on concentrations of Hg and Se in five cetacean species from the Adriatic Sea basin.

  16. A hybrid approach to advancing quantitative prediction of tissue distribution of basic drugs in human

    International Nuclear Information System (INIS)

    Poulin, Patrick; Ekins, Sean; Theil, Frank-Peter

    2011-01-01

    A general toxicity of basic drugs is related to phospholipidosis in tissues. Therefore, it is essential to predict the tissue distribution of basic drugs to facilitate an initial estimate of that toxicity. The objective of the present study was to further assess the original prediction method that consisted of using the binding to red blood cells measured in vitro for the unbound drug (RBCu) as a surrogate for tissue distribution, by correlating it to unbound tissue:plasma partition coefficients (Kpu) of several tissues, and finally to predict volume of distribution at steady-state (V ss ) in humans under in vivo conditions. This correlation method demonstrated inaccurate predictions of V ss for particular basic drugs that did not follow the original correlation principle. Therefore, the novelty of this study is to provide clarity on the actual hypotheses to identify i) the impact of pharmacological mode of action on the generic correlation of RBCu-Kpu, ii) additional mechanisms of tissue distribution for the outlier drugs, iii) molecular features and properties that differentiate compounds as outliers in the original correlation analysis in order to facilitate its applicability domain alongside the properties already used so far, and finally iv) to present a novel and refined correlation method that is superior to what has been previously published for the prediction of human V ss of basic drugs. Applying a refined correlation method after identifying outliers would facilitate the prediction of more accurate distribution parameters as key inputs used in physiologically based pharmacokinetic (PBPK) and phospholipidosis models.

  17. Controlled delivery of antiangiogenic drug to human eye tissue using a MEMS device

    KAUST Repository

    Pirmoradi, Fatemeh Nazly

    2013-01-01

    We demonstrate an implantable MEMS drug delivery device to conduct controlled and on-demand, ex vivo drug transport to human eye tissue. Remotely operated drug delivery to human post-mortem eyes was performed via a MEMS device. The developed curved packaging cover conforms to the eyeball thereby preventing the eye tissue from contacting the actuating membrane. By pulsed operation of the device, using an externally applied magnetic field, the drug released from the device accumulates in a cavity adjacent to the tissue. As such, docetaxel (DTX), an antiangiogenic drug, diffuses through the eye tissue, from sclera and choroid to retina. DTX uptake by sclera and choroid were measured to be 1.93±0.66 and 7.24±0.37 μg/g tissue, respectively, after two hours in pulsed operation mode (10s on/off cycles) at 23°C. During this period, a total amount of 192 ng DTX diffused into the exposed tissue. This MEMS device shows great potential for the treatment of ocular posterior segment diseases such as diabetic retinopathy by introducing a novel way of drug administration to the eye. © 2013 IEEE.

  18. Concentrations of danofloxacin 18% solution in plasma, milk and tissues after subcutaneous injection in dairy cows

    International Nuclear Information System (INIS)

    Mestorino, N.; Marchetti, M.L.; Turic, E.; Pesoa, J.; Errecalde, J.

    2009-01-01

    Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mg kg -1 ). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 μg h mL -1 and its elimination half life (T β 1/2 ) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T β 1/2 from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal

  19. Cryopreservation of Precision-cut Tissue Slices for Application in Drug Metabolism Research

    NARCIS (Netherlands)

    Graaf, Inge Anne Maria de

    2002-01-01

    The research described in this thesis had two important aims. The first was to determine whether tissue slices could be used as an in vitro tool to predict the in vivo metabolism of new drugs. The second aim was to find a manner to store tissue slices for longer time periods by cryopreservation.

  20. A dynamic model to calculate cadmium concentrations in bovine tissues from basic soil characteristics

    International Nuclear Information System (INIS)

    Waegeneers, Nadia; Ruttens, Ann; De Temmerman, Ludwig

    2011-01-01

    A chain model was developed to calculate the flow of cadmium from soil, drinking water and feed towards bovine tissues. The data used for model development were tissue Cd concentrations of 57 bovines and Cd concentrations in soil, feed and drinking water, sampled at the farms were the bovines were reared. Validation of the model occurred with a second set of measured tissue Cd concentrations of 93 bovines of which age and farm location were known. The exposure part of the chain model consists of two parts: (1) a soil-plant transfer model, deriving cadmium concentrations in feed from basic soil characteristics (pH and organic matter content) and soil Cd concentrations, and (2) bovine intake calculations, based on typical feed and water consumption patterns for cattle and Cd concentrations in feed and drinking water. The output of the exposure model is an animal-specific average daily Cd intake, which is then taken forward to a kinetic uptake model in which time-dependent Cd concentrations in bovine tissues are calculated. The chain model was able to account for 65%, 42% and 32% of the variation in observed kidney, liver and meat Cd concentrations in the validation study. - Research highlights: → Cadmium transfer from soil, drinking water and feed to bovine tissues was modeled. → The model was based on 57 bovines and corresponding feed and soil Cd concentrations. → The model was validated with an independent data set of 93 bovines. → The model explained 65% of variation in kidney Cd in the validation study.

  1. Relationships of mercury concentrations across tissue types, muscle regions and fins for two shark species

    KAUST Repository

    O'Bryhim, Jason R.

    2017-01-31

    Mercury (Hg) exposure poses a threat to both fish and human health. Sharks are known to bioaccumulate Hg, however, little is known regarding how Hg is distributed between different tissue groups (e.g. muscle regions, organs). Here we evaluated total mercury (THg) concentrations from eight muscle regions, four fins (first dorsal, left and right pectorals, caudal-from both the inner core and trailing margin of each fin), and five internal organs (liver, kidney, spleen, heart, epigonal organ) from two different shark species, bonnethead (Sphyrna tiburo) and silky shark (Carcharhinus falciformis) to determine the relationships of THg concentrations between and within tissue groups. Total Hg concentrations were highest in the eight muscle regions with no significant differences in THg concentrations between the different muscle regions and muscle types (red and white). Results from tissue collected from any muscle region would be representative of all muscle sample locations. Total Hg concentrations were lowest in samples taken from the fin inner core of the first dorsal, pectoral, and caudal (lower lobe) fins. Mercury concentrations for samples taken from the trailing margin of the dorsal, pectoral, and caudal fins (upper and lower lobe) were also not significantly different from each other for both species. Significant relationships were found between THg concentrations in dorsal axial muscle tissue and the fin inner core, liver, kidney, spleen and heart for both species as well as the THg concentrations between the dorsal fin trailing margin and the heart for the silky shark and all other sampled tissue types for the bonnethead shark. Our results suggest that biopsy sampling of dorsal muscle can provide data that can effectively estimate THg concentrations in specific organs without using more invasive, or lethal methods.

  2. Microfluidics Enables Small-Scale Tissue-Based Drug Metabolism Studies With Scarce Human Tissue

    NARCIS (Netherlands)

    van Midwoud, Paul M.; Verpoorte, Elisabeth; Groothuis, Geny M. M.; Merema, M.T.

    2011-01-01

    Early information on the metabolism and toxicity properties of new drug candidates is crucial for selecting the right candidates for further development. Preclinical trials rely on cell-based in vitro tests and animal studies to characterize the in vivo behavior of drug candidates, although neither

  3. Stimuli-responsive hydrogels in drug delivery and tissue engineering.

    Science.gov (United States)

    Sood, Nikhil; Bhardwaj, Ankur; Mehta, Shuchi; Mehta, Abhinav

    2016-01-01

    Hydrogels are the three-dimensional network structures obtained from a class of synthetic or natural polymers which can absorb and retain a significant amount of water. Hydrogels are one of the most studied classes of polymer-based controlled drug release. These have attracted considerable attention in biochemical and biomedical fields because of their characteristics, such as swelling in aqueous medium, biocompatibility, pH and temperature sensitivity or sensitivity towards other stimuli, which can be utilized for their controlled zero-order release. The hydrogels are expected to explore new generation of self-regulated delivery system having a wide array of desirable properties. This review highlights the exciting opportunities and challenges in the area of hydrogels. Here, we review different literatures on stimuli-sensitive hydrogels, such as role of temperature, electric potential, pH and ionic strength to control the release of drug from hydrogels.

  4. Elemental concentration analysis in prostate tissues using total reflection X-ray fluorescence

    International Nuclear Information System (INIS)

    Leitão, R.G.; Palumbo, A.; Souza, P.A.V.R.; Pereira, G.R.; Canellas, C.G.L.; Anjos, M.J.; Nasciutti, L.E.; Lopes, R.T.

    2014-01-01

    Prostate cancer (PCa) currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer, BPH and normal tissue were analyzed utilizing total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SR-TXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, São Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn and Rb. By using Mann–Whitney U test it was observed that almost all elements presented concentrations with significant differences (α=0.05) between the groups studied. - Highlights: ► Prostate cancer is the most frequently diagnosed form of cancer in men. ► Intracellular Zn is correlated with proliferation, differentiation, or apoptosis. ► The prostate gland accumulate high concentration of Zn. ► SR-TXRF is a technique widely used in the analysis of low concentration in samples

  5. Mapping absolute tissue endogenous fluorophore concentrations with chemometric wide-field fluorescence microscopy

    Science.gov (United States)

    Xu, Zhang; Reilley, Michael; Li, Run; Xu, Min

    2017-06-01

    We report chemometric wide-field fluorescence microscopy for imaging the spatial distribution and concentration of endogenous fluorophores in thin tissue sections. Nonnegative factorization aided by spatial diversity is used to learn both the spectral signature and the spatial distribution of endogenous fluorophores from microscopic fluorescence color images obtained under broadband excitation and detection. The absolute concentration map of individual fluorophores is derived by comparing the fluorescence from "pure" fluorophores under the identical imaging condition following the identification of the fluorescence species by its spectral signature. This method is then demonstrated by characterizing the concentration map of endogenous fluorophores (including tryptophan, elastin, nicotinamide adenine dinucleotide, and flavin adenine dinucleotide) for lung tissue specimens. The absolute concentrations of these fluorophores are all found to decrease significantly from normal, perilesional, to cancerous (squamous cell carcinoma) tissue. Discriminating tissue types using the absolute fluorophore concentration is found to be significantly more accurate than that achievable with the relative fluorescence strength. Quantification of fluorophores in terms of the absolute concentration map is also advantageous in eliminating the uncertainties due to system responses or measurement details, yielding more biologically relevant data, and simplifying the assessment of competing imaging approaches.

  6. Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device

    Directory of Open Access Journals (Sweden)

    Jeffrey T. Borenstein

    2012-03-01

    Full Text Available The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene (PTFE membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation.

  7. Overcoming cellular and tissue barriers to improve liposomal drug delivery

    Science.gov (United States)

    Kohli, Aditya G.

    Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

  8. Mitomycin C dissolved in a reversible thermosetting gel: target tissue concentrations in the rabbit eye.

    Science.gov (United States)

    Ichien, K; Yamamoto, T; Kitazawa, Y; Oguri, A; Ando, H; Kondo, Y

    1997-01-01

    To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye. A 0.1 ml solution of mitomycin C containing 0.22 microgram, 2.9 micrograms, or 28 micrograms of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated. The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used. Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva.

  9. Examination of rare earth element concentration patterns in freshwater fish tissues.

    Science.gov (United States)

    Mayfield, David B; Fairbrother, Anne

    2015-02-01

    Rare earth elements (REEs or lanthanides) were measured in ten freshwater fish species from a reservoir in Washington State (United States). The REE distribution patterns were examined within fillet and whole body tissues for three size classes. Total concentrations (ΣREE) ranged from 0.014 to 3.0 mg kg(-1) (dry weight) and averaged 0.243 mg kg(-1) (dry weight). Tissue concentration patterns indicated that REEs accumulated to a greater extent in organs, viscera, and bone compared to muscle (fillet) tissues. Benthic feeding species (exposed to sediments) exhibited greater concentrations of REEs than pelagic omnivorous or piscivorous fish species. Decreasing REE concentrations were found with increasing age, total length or weight for largescale and longnose suckers, smallmouth bass, and walleye. Concentration patterns in this system were consistent with natural conditions without anthropogenic sources of REEs. These data provide additional reference information with regard to the fate and transport of REEs in freshwater fish tissues in a large aquatic system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  11. Natural U concentrations in soft tissues and bone of New York City residents

    International Nuclear Information System (INIS)

    Fisenne, I.M.; Welford, G.A.

    1986-01-01

    Specimens of lung, liver, kidney and vertebrae from New York City autopsy cases were measured for naturally occurring U. An age dependency in U concentration was found in lung and vertebrae. The bone concentration was found to be a factor of 10 lower than previously reported for this tissue, thus the skeletal burden of U is estimated to be factor of 10 lower than that suggested in ICRP Publication 23

  12. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue

    DEFF Research Database (Denmark)

    Nielsen, Ninna Bo; Højbjerre, Lise; Sonne, Mette P

    2009-01-01

    Adipokines play important regulatory roles in the pathophysiology of obesity and insulin resistance. We measured plasma and interstitial concentrations of the adipokines adiponectin, resistin, leptin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8...... plasma (approximately 100-fold, approximately 200-fold and approximately 1000-fold, respectively, PResistin concentrations did not differ significantly between compartments. Adipose tissue blood flow (ATBF) showed no regional difference (P>0.05). The intra- and inter-subject variations of all...

  13. Biomacromolecules as carriers in drug delivery and tissue engineering.

    Science.gov (United States)

    Zhang, Yujie; Sun, Tao; Jiang, Chen

    2018-01-01

    Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.

  14. Metal concentrations in homing pigeon lung tissue as a biomonitor of atmospheric pollution.

    Science.gov (United States)

    Cui, Jia; Halbrook, Richard S; Zang, Shuying; Han, Shuang; Li, Xinyu

    2018-03-01

    Atmospheric pollution in urban areas is a major worldwide concern with potential adverse impacts on wildlife and humans. Biomonitoring can provide direct evidence of the bioavailability and bioaccumulation of toxic metals in the environment that is not available with mechanical air monitoring. The current study continues our evaluation of the usefulness of homing pigeon lung tissue as a biomonitor of atmospheric pollution. Homing pigeons (1-2, 5-6, and 9-10+ year old (yo)) collected from Guangzhou during 2015 were necropsied and concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were measured in lung tissue. Lung Cd and Pb concentrations were significantly greater in 9-10+-year-old pigeons compared with those in other age groups, indicating their bioavailability and bioaccumulation. Lung Pb and Cd concentrations measured in 5-yo pigeons collected from Guangzhou during 2015 were significantly lower than concentrations reported in 5-yo homing pigeons collected from Guangzhou during 2011 and correlated with concentrations measured using mechanical air monitoring. In addition to temporal differences, spatial differences in concentrations of Cd, Pb, and Hg reported in ambient air samples and in pigeon lung tissues collected from Beijing and Guangzhou are discussed.

  15. Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Sofia Dias

    2018-01-01

    Full Text Available Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide on adipose tissue. Specifically, we explored how these drugs can modulate the complex pathways involved in metabolism, inflammation, atherogenesis, insulin sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation by these drugs, as well as differences of major importance for clinical practice between drugs of the same class, were identified. Whether solutions to these issues will be found in further adjustments and combinations between drugs already in use or necessarily in new advances in pharmacology is not known. To better understand the effect of drugs used in dyslipidemia and obesity on adipose tissue not only is challenging for physicians but could also be the next step to tackle cardiovascular disease.

  16. Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Rosenzweig, Mary; Dela, Flemming

    2007-01-01

    -) plasma concentration did not change during exercise in any of the groups, but SCAAT TNF- mRNA increased after exercise in both groups. Furthermore, exercise decreased SCAAT leptin mRNA with no change in resistin mRNA. CONCLUSIONS: Acute exercise increases adipose tissue interstitial adiponectin...

  17. POSSIBLE RAMIFICATIONS OF HIGHER MERCURY CONCENTRATIONS IN FILLET TISSUE OF SKINNIER FISH

    Science.gov (United States)

    Mercury concentrations were found to be statistically higher in the fillet tissue of the skinnier individuals of a fish species (striped bass) that was experiencing starvation when collected from Lake Mead, which is located on the Arizona-Nevada border. This is considered a conse...

  18. Elemental concentration analysis in PCa, BPH and normal prostate tissues using SR-TXRF

    International Nuclear Information System (INIS)

    Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Lopes, Ricardo T.

    2009-01-01

    Prostate cancer (PCa) is one of the main causes of illness and death all over the world. In Brazil, prostate cancer currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer (PCa), BPH and normal tissue were analyzed utilizing the total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SRTXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-Ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn, Br and Rb. By using Mann-Whitney U test it was observed that almost all elements presented concentrations with significant differences α = 0.05) between the groups studied. The elements and groups were: S, K, Ca, Fe, Zn, Br and Rb (PCa X Normal); S, Fe, Zn and Br (PCa X BPH); K, Ca, Fe, Zn, Br and Rb (BPH X Normal). (author)

  19. Teeth as biomonitors of selenium concentrations in tissues of beluga whales (Delphinapterus leucas)

    International Nuclear Information System (INIS)

    Kinghorn, April; Humphries, Murray M.; Outridge, Peter; Chan, Hing Man

    2008-01-01

    Selenium (Se) is an essential element which has been shown to play an important role in protecting marine mammals against the toxic effects of mercury (Hg) and other metals. It has been suggested that metal concentration in marine mammal teeth can potentially be used as bioindicators for body burden. The objective of this study was to investigate the relationship between Se concentrations in beluga (Delphinapterus leucas) teeth and those previously measured in soft tissues (liver, kidney, muscle and muktuk). Tooth Hg concentrations are also measured, and the relationships between Se and Hg in teeth and soft tissues are examined. Se in the teeth of beluga was measured using hydride generation atomic fluorescence spectrometry (HG-AFS) and Hg in beluga teeth was measured by cold-vapour atomic absorption. Tooth Se concentrations ranged from 108 ng/g to 245 ng/g dry weight, and tooth Hg concentrations ranged from 10 to 189 ng/g dry weight. In the soft tissues, Se concentrations were highest in the liver, followed by kidney, muktuk, and muscle. There were significant correlations between tooth Se concentrations and animal age, tooth Se and liver and muscle Se, and between liver Se and animal age. The molar ratio of Hg:Se in the liver was found to be 0.70. This study is the first to measure Se in the teeth of a marine mammal species, and HG-AFS is found to be an effective technique for determining Se in beluga teeth. Tooth Se can be used as predictor for liver and muscle Se, although these relationships may be strongly influenced by the association of Se with Hg in marine mammal tissues. This study contributes to an increased understanding of the storage and metabolism of Se in marine mammals

  20. Teeth as biomonitors of selenium concentrations in tissues of beluga whales (Delphinapterus leucas)

    Energy Technology Data Exchange (ETDEWEB)

    Kinghorn, April [Centre for Indigenous Peoples Nutrition and Environment, Macdonald Campus, McGill University, 21-111 Lakeshore Road, Ste. Anne-de-Bellevue, Quebec, H9X 3V9 (Canada); Humphries, Murray M. [Centre for Indigenous Peoples Nutrition and Environment, Macdonald Campus, McGill University, 21-111 Lakeshore Road, Ste. Anne-de-Bellevue, Quebec, H9X 3V9 (Canada); Department of Natural Resource Science, Macdonald Campus, McGill University, 21-111 Lakeshore Road, Ste. Anne-de-Bellevue, Quebec, H9X 3V9 (Canada); Outridge, Peter [Geological Survey of Canada, 601 Booth Street, Ottawa, Ontario, K1A 0E8 (Canada); Chan, Hing Man [Community Health Sciences Program, University of Northern British Columbia, 3333 University Way, Prince George, British Columbia, V2N 4Z9 (Canada)], E-mail: lchan@unbc.ca

    2008-08-25

    Selenium (Se) is an essential element which has been shown to play an important role in protecting marine mammals against the toxic effects of mercury (Hg) and other metals. It has been suggested that metal concentration in marine mammal teeth can potentially be used as bioindicators for body burden. The objective of this study was to investigate the relationship between Se concentrations in beluga (Delphinapterus leucas) teeth and those previously measured in soft tissues (liver, kidney, muscle and muktuk). Tooth Hg concentrations are also measured, and the relationships between Se and Hg in teeth and soft tissues are examined. Se in the teeth of beluga was measured using hydride generation atomic fluorescence spectrometry (HG-AFS) and Hg in beluga teeth was measured by cold-vapour atomic absorption. Tooth Se concentrations ranged from 108 ng/g to 245 ng/g dry weight, and tooth Hg concentrations ranged from 10 to 189 ng/g dry weight. In the soft tissues, Se concentrations were highest in the liver, followed by kidney, muktuk, and muscle. There were significant correlations between tooth Se concentrations and animal age, tooth Se and liver and muscle Se, and between liver Se and animal age. The molar ratio of Hg:Se in the liver was found to be 0.70. This study is the first to measure Se in the teeth of a marine mammal species, and HG-AFS is found to be an effective technique for determining Se in beluga teeth. Tooth Se can be used as predictor for liver and muscle Se, although these relationships may be strongly influenced by the association of Se with Hg in marine mammal tissues. This study contributes to an increased understanding of the storage and metabolism of Se in marine mammals.

  1. Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs.

    Science.gov (United States)

    Santos, Mónica S F; Franquet-Griell, Helena; Lacorte, Silvia; Madeira, Luis M; Alves, Arminda

    2017-10-01

    Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PEC b > 10 ng L -1 and/or PEC c > 1 ng L -1 ). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Carvedilol induces endogenous hydrogen sulfide tissue concentration changes in various mouse organs.

    Science.gov (United States)

    Wiliński, Bogdan; Wiliński, Jerzy; Somogyi, Eugeniusz; Piotrowska, Joanna; Góralska, Marta; Macura, Barbara

    2011-01-01

    Carvedilol, a third generation non-selective adrenoreceptor blocker, is widely used in cardiology. Its action has been proven to reach beyond adrenergic antagonism and involves multiple biological mechanisms. The interaction between carvedilol and endogenous 'gasotransmitter' hydrogen sulfide (H2S) is unknown. The aim of the study is to assess the influence of carvedilol on the H2S tissue level in mouse brain, liver, heart and kidney. Twenty eight SJL strain female mice were administered intraperitoneal injections of 2.5 mg/kg b.w./d (group D1, n=7), 5 mg/kg b.w./d (group D2, n=7) or 10 mg/kg b.w./d of carvedilol (group D3, n=7). The control group (n=7) received physiological saline in portions of the same volume (0.2 ml). Measurements of the free tissue H2S concentrations were performed according to the modified method of Siegel. A progressive decline in H2S tissue concentration along with an increase in carvedilol dose was observed in the brain (12.5%, 13.7% and 19.6%, respectively). Only the highest carvedilol dose induced a change in H2S tissue level in the heart - an increase by 75.5%. In the liver medium and high doses of carvedilol increased the H2S level by 48.1% and 11.8%, respectively. In the kidney, group D2 showed a significant decrease of H2S tissue level (22.5%), while in the D3 group the H2S concentration increased by 12.9%. Our study has proven that carvedilol affects H2S tissue concentration in different mouse organs.

  3. Prolactin suppresses malonyl-CoA concentration in human adipose tissue

    DEFF Research Database (Denmark)

    Nilsson, L. A.; Roepstorff, Carsten; Kiens, Bente

    2009-01-01

    Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however......, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77......+/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue...

  4. A PIXE analysis for measuring the trace elements concentration in breast tissue of Iranian women

    International Nuclear Information System (INIS)

    Vatankhah, S.; Moosavi, K.; Salimi, J.; Geranpayeh, L.; Perovani, H.

    2003-01-01

    A powerful and improved technique, proton induced x-ray emission has been performed-yielding the elemental composition of 17 samples of surgically excised malignant and normal tumors of breast tissue. The samples without any further process as thick targets were put on cap ton foil backing. There are no homogenizing processes. The proton induced x-ray emission spectra analysis was performed using he non-linear least square fitting code AXIL and GUPIX. The samples are taken form patients in the wide range of age and are bombarded by 2.0 MeV energy proton beams produced by van de Graaff accelerator in vacuum. The quantitative comparison between two of tissue was evaluated by assessing the presence of calcium. Potassium, Iron, Copper and Zinc, as minor and trace elements. results in this study indicate that relative values of Cu/Zn, P/K and also Ca and S in being type were higher than those in those in malignant type, but the concentration of Fe and Zn in cancerous tissues was significantly higher than those for being type. Results suggest significant elevation of zinc in the pathological tissues. Cu/Zn ratio for both type of tissues are evaluated. The results show that this ratio in patients with breast cancer is significantly lower than the normal group. Selenium and arsenic was not obtained in any of 17 samples. Most of the tissues of benign kind (fibrocystic and fib ro adenoma)contain cadmium. Calcium concentration in normal tissues is significantly higher than tumorous tissues

  5. Increased concentration of. cap alpha. - and. gamma. -endorphin in post mortem hypothalamic tissue of schizophrenic patients

    Energy Technology Data Exchange (ETDEWEB)

    Wiegant, V.M.; Verhoef, C.J.; Burbach, J.P.H.; de Wied, D.

    1988-01-01

    The concentrations of ..cap alpha..-, ..beta..- and ..gamma..-endorphin were determined by radioimmunoassay in HPLC fractionated extracts of post mortem hypothalamic tissue obtained from schizophrenic patients and controls. The hypothalamic concentration of ..cap alpha..- and ..gamma..-endorphin was significantly higher in patients than in controls. No difference was found in the concentration of ..beta..-endorphin, the putative precursor of ..cap alpha..- and ..gamma..-endorphins. These results suggest a deviant metabolism of ..beta..-endorphin in the brain of schizophrenic patients. Whether this phenomenon is related to the psychopathology, or is a consequence of ante mortem farmacotherapy, remains to be established.

  6. Comparison of spectroscopically measured tissue alcohol concentration to blood and breath alcohol measurements

    Science.gov (United States)

    Ridder, Trent D.; Ver Steeg, Benjamin J.; Laaksonen, Bentley D.

    2009-09-01

    Alcohol testing is an expanding area of interest due to the impacts of alcohol abuse that extend well beyond drunk driving. However, existing approaches such as blood and urine assays are hampered in some testing environments by biohazard risks. A noninvasive, in vivo spectroscopic technique offers a promising alternative, as no body fluids are required. The purpose of this work is to report the results of a 36-subject clinical study designed to characterize tissue alcohol measured using near-infrared spectroscopy relative to venous blood, capillary blood, and breath alcohol. Comparison of blood and breath alcohol concentrations demonstrated significant differences in alcohol concentration [root mean square of 9.0 to 13.5 mg/dL] that were attributable to both assay accuracy and precision as well as alcohol pharmacokinetics. A first-order kinetic model was used to estimate the contribution of alcohol pharmacokinetics to the differences in concentration observed between the blood, breath, and tissue assays. All pair-wise combinations of alcohol assays were investigated, and the fraction of the alcohol concentration variance explained by pharmacokinetics ranged from 41.0% to 83.5%. Accounting for pharmacokinetic concentration differences, the accuracy and precision of the spectroscopic tissue assay were found to be comparable to those of the blood and breath assays.

  7. The toxicological significance of post-mortem drug concentrations in bile.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2018-01-01

    Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature. We made a systematic search of EMBASE 1980-2016 using the search terms ("bile/" OR "exp drug bile level/concentration/") AND "drug blood level/concentration/", PubMed 1975-2017 for ("bile[tw]" OR "biliary[tw]") AND ("concentration[tw]" OR "concentrations[tw]" OR "level[tw]" OR "levels[tw]") AND "post-mortem[tw]" and also MEDLINE 1990-2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs. Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058-0.32) for dextromoramide to 520 (range 0.62-43,000) for buprenorphine. Median bile

  8. Bioprinting of Micro-Organ Tissue Analog for Drug Metabolism Study

    Science.gov (United States)

    Sun, Wei

    An evolving application of tissue engineering is to develop in vitro 3D cell/tissue models for drug screening and pharmacological study. In order to test in space, these in vitro models are mostly manufactured through micro-fabrication techniques and incorporate living cells with MEMS or microfluidic devices. These cell-integrated microfluidic devices, or referred as microorgans, are effective in furnishing reliable and inexpensive drug metabolism and toxicity studies [1-3]. This paper will present an on-going research collaborated between Drexel University and NASA JSC Radiation Physics Laboratory for applying a direct cell printing technique to freeform fabrication of 3D liver tissue analog in drug metabolism study. The paper will discuss modeling, design, and solid freeform fabrication of micro-fluidic flow patterns and bioprinting of 3D micro-liver chamber that biomimics liver physiological microenvironment for enhanced drug metabolization. Technical details to address bioprinting of 3D liver tissue analog, integration with a microfluidic device, and basic drug metabolism study for NASA's interests will presented. 1. Holtorf H. Leslie J. Chang R, Nam J, Culbertson C, Sun W, Gonda S, "Development of a Three-Dimensional Tissue-on-a-Chip Micro-Organ Device for Pharmacokinetic Analysis", the 47th Annual Meeting of the American Society for Cell Biology, Washington, DC, December 1-5, 2007. 2. Chang, R., Nam, J., Culbertson C., Holtorf, H., Jeevarajan, A., Gonda, S. and Sun, W., "Bio-printing and Modeling of Flow Patterns for Cell Encapsulated 3D Liver Chambers For Pharmacokinetic Study", TERMIS North America 2007 Conference and Exposition, Westin Harbour Castle, Toronto, Canada, June 13-16, 2007. 3.Starly, B., Chang, R., Sun, W., Culbertson, C., Holtorf, H. and Gonda, S., "Bioprinted Tissue-on-chip Application for Pharmacokinetic Studies", Proceedings of World Congress on Tissue Engineering and Regenerative Medicine, Pittsburgh, PA, USA, April 24-27, 2006.

  9. Suspended particle and drug ingredient concentrations in hospital dispensaries and implications for pharmacists' working environments.

    Science.gov (United States)

    Inaba, Ryoichi; Hioki, Atsushi; Kondo, Yoshihiro; Nakamura, Hiroki; Nakamura, Mitsuhiro

    2016-03-01

    The aim of this study was to assess the present status of working environments for pharmacists, including the concentrations of suspended particles and suspended drug ingredients in dispensaries. We conducted a survey on the work processes and working environment in 15 hospital dispensaries, and measured the concentrations of suspended particles and suspended drug ingredients using digital dust counter and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Of 25 types of powdered drugs that were frequently handled in the 15 dispensaries surveyed, 11 could be quantitatively determined. The amounts of suspended particles were relatively high, but below the reference value, in three dispensaries without dust collectors. The sedative-hypnotic drug zopiclone was detected in the suspended particles at one dispensary that was not equipped with dust collectors, and the antipyretic and analgesic drug acetaminophen was detected in two dispensaries equipped with dust collectors. There was no correlation between the daily number of prescriptions containing powdered drugs and the concentration of suspended particles in dispensaries. On the basis of the suspended particle concentrations measured, we concluded that dust collectors were effective in these dispensaries. However, suspended drug ingredients were detected also in dispensaries with dust collectors. These results suggest that the drug dust control systems of individual dispensaries should be properly installed and managed.

  10. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    International Nuclear Information System (INIS)

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-01-01

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  11. Concentration Levels of Imidacloprid and Dinotefuran in Five Tissue Types of Black Walnut, Juglans nigra

    Directory of Open Access Journals (Sweden)

    Paul Merten

    2013-11-01

    Full Text Available Black walnut, a valuable economic and environmentally important species, is threatened by thousand cankers disease. Systemic imidacloprid and dinotefuran applications were made to mature black walnut trees to evaluate their translocation and concentration levels in various tissue types including leaf, twig, trunk core, nutmeat, and walnut husk. The metabolism of imidacloprid in plants produces a metabolite, olefin-imidacloprid, which has been documented to have insecticidal properties in other systems. Trunk CoreTect (imidacloprid soil pellets and a trunk spray of dinotefuran were applied to mature black walnuts in spring 2011. Imidacloprid concentrations were detected in both the lower and upper strata in all tissue types tested and progressively increased through month 12 post-treatment in twig and leaf tissue. Olefin-imidacloprid was detected in the nutmeat and walnut husk. Dinotefuran was only detected in the first sampling period and was found in low concentration levels in leaf and twig tissue types, and was not detected in the trunk, nutmeat or the walnut husk.

  12. Concentrations of Polybrominated Diphenyl Ethers (PBDEs) and 2,4,6-Tribromophenol in Human Placental Tissues

    Science.gov (United States)

    Leonetti, Christopher; Butt, Craig M.; Hoffman, Kate; Miranda, Marie Lynn; Stapleton, Heather M.

    2015-01-01

    Legacy environmental contaminants such as polybrominated diphenyl ethers (PBDEs) are widely detected in human tissues. However, few studies have measured PBDEs in placental tissues, and there are no reported measurements of 2,4,6-tribromophenol (2,4,6-TBP) in placental tissues. Measurements of these contaminants are important for understanding potential fetal exposures, as these compounds have been shown to alter thyroid hormone regulation in vitro and in vivo. In this study, we measured a suite of PBDEs and 2,4,6-TBP in 102 human placental tissues collected between 2010–2011 in Durham County, North Carolina, USA. The most abundant PBDE congener detected was BDE-47, with a mean concentration of 5.09 ng/g lipid (range: 0.12–141 ng/g lipid; detection frequency 91%); however, 2,4,6-TBP was ubiquitously detected and present at higher concentrations with a mean concentration of 15.4 ng/g lipid (range:1.31–316 ng/g lipid; detection frequency 100%). BDE-209 was also detected in more than 50% of the samples, and was significantly associated with 2,4,6-TBP in placental tissues, suggesting they may have a similar source, or that 2,4,6-TBP may be a degradation product of BDE-209. Interestingly, BDE-209 and 2,4,6-TBP were negatively associated with age (rs=−0.16; p=0.10 and rs=−0.17; p=0.08, respectively). The results of this work indicate that PBDEs and 2,4,6-TBP bioaccumulate in human placenta tissue and likely contribute to prenatal exposures to these environmental contaminants. Future studies are needed to determine if these joint exposures are associated with any adverse health measures in infants and children. PMID:26700418

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maxime Reverchon

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

  15. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

    Science.gov (United States)

    Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

    2013-11-18

    Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  16. Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

    Science.gov (United States)

    Labib, Gihan

    2018-01-01

    Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

  17. Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution.

    Science.gov (United States)

    Rosenbaum, M; Pietrobelli, A; Vasselli, J R; Heymsfield, S B; Leibel, R L

    2001-09-01

    Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17+/-0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/-3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are

  18. Discriminant analysis of normal and malignant breast tissue based upon INAA investigation of elemental concentration

    International Nuclear Information System (INIS)

    Kwanhoong Ng; Senghuat Ong; Bradley, D.A.; Laimeng Looi

    1997-01-01

    Discriminant analysis of six trace element concentrations measured by instrumental neutron activation analysis (INAA) in 26 paired-samples of malignant and histologically normal human breast tissues shows the technique to be a potentially valuable clinical tool for making malignant-normal classification. Nonparametric discriminant analysis is performed for the data obtained. Linear and quadratic discriminant analyses are also carried out for comparison. For this data set a formal analysis shows that the elements which may be useful in distinguishing between malignant and normal tissues are Ca, Rb and Br, providing correct classification for 24 out of 26 normal samples and 22 out of 26 malignant samples. (Author)

  19. Effects of different concentrations of pollen extract on brain tissues of Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Mehmet Fuat Gulhan

    2014-03-01

    Full Text Available Objective: To determine the antioxidant capacities of pollen extract applied at different concentrations on biochemical parameters in brain tissues of rainbow trouts. Methods: The effective concentration of pollen was determined with some biochemical parameters in brain tissues of fish treated at various concentrations of the pollen extract (0.5, 2.5, 5, 10, 20 and 30 mg/L for 96 h. The malondialdehyde levels, total antioxidant status, total oxidant status, oxidative stress index and amounts of total free sulfhydryl groups were analyzed in fish brain. Results: The malondialdehyde levels decreased in groups of 0.5, 2.5, 5, 10, 20 and 30 mg/L pollen-treated compared to control group (P<0.05. The highest level of total antioxidant status (P<0.05 and the lowest value (P<0.05 of the total oxidant status was 10 mg/L concentration of pollen. Oxidative stress index and level of sulfhydryl groups showed lowest values (P<0.05 in 10 mg/L pollen treated group compared with control group. Conclusions: To apply the pollen to fish reduces the detrimental effects and modulates oxidative status via activating antioxidant defense systems at brain tissue. As a result, pollen can be added up to 10 mg/L to the medium of rainbow trout to improve health of fish.

  20. Use and abuse of trace metal concentrations in plant tissue for biomonitoring and phytoextraction

    International Nuclear Information System (INIS)

    Mertens, Jan; Luyssaert, Sebastiaan; Verheyen, Kris

    2005-01-01

    Some plant species accumulate trace metals from the soil in their aboveground biomass. Therefore, some scientists have concluded that these species are suitable for biomonitoring trace metal concentrations in the soil or for removing excessive trace metals from the soil by means of phytoextraction. A significant correlation between the chemical composition of foliage and soil is not a sufficient condition for using the chemical composition of foliage as a biomonitor for the quality of the soil. The chemical composition of foliage can, however, provide additional information to the traditional soil samples. The phytoextraction potential of a plant species cannot solely be evaluated on the basis of the trace metal concentrations in the plant and soil tissue. Data on the depth of the rooting zone, the density of the soil and the harvestable biomass should also be taken into account. Although plant tissue analysis is a useful tool in a wide range of studies and applications, trace metal concentrations in plant tissue cannot be viewed in isolation. Instead it should be analysed and interpreted in relation to other information such as soil concentrations, rooted zone, biomass production, etc. - Plants that accumulate soil metals in their aboveground biomass are often incorrectly considered to be suitable for monitoring soil pollution or for phytoextraction purposes

  1. THE MAIN NUTRIENTS CONCENTRATION FROM INTRA TISSUE WATER OF BENTHOS ORAGANISMS FROM MURES BASIN

    Directory of Open Access Journals (Sweden)

    DANA POPA

    2008-05-01

    Full Text Available In the hydrographic basin of Mures river, aboard an altitude gradient, were taken samples of intra tissue waters from benthonic organisms for research the nutrients concentrations. The reference point was represented by a dairy caw farm where the agricultural fields of this is applied the organic fertilization with manure. The intra tissue water samples from benthonic organisms were prelevated in spring and autumn and the prelevate dates are the same with spread manure dates. At the intra tissue water level, concentrations value of N and P are bigger at the second data prelevations than first data prelevations and we can conclude that the benthonic oligochetas activity increase, more than, they density increase in Mures basin. The high concentrations of NH4 show as that Mures basin is a zone characterized by high degree of anoxia and this fact is supported by significant differences between seasonal prelevations. The explication is the manifestation to the cumulated and at distance effects of introduction in water to some organic products, very probably washed from neighborhoods agricultural field. Were calculated values of Student test for seasonal comparisons and were founded significant differences between nutrients concentration values at first and second prelevations.

  2. The frequency of drugs among Danish drivers before and after the introduction of fixed concentration limits

    DEFF Research Database (Denmark)

    Steentoft, Anni; Simonsen, Kirsten Wiese; Linnet, Kristian

    2010-01-01

    Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective...... for this study was to investigate the prevalence of medication and illicit drugs among Danish drivers before and after 2007.......Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective...

  3. [Studies on antimicrobial concentrations of flomoxef in serum, pelvic dead space exudate, and pelvic organs/tissues].

    Science.gov (United States)

    Obata, T; Koishi, K; Sasaki, J; Eguchi, M; Yamamoto, Y

    1987-10-01

    To women undergoing radical and total hysterectomy, flomoxef (FMOX, 6315-S) in a dose of 2 g was administered by intravenous drip infusion over 1 hour and drug concentrations in serum and pelvic dead space exudate as well as pelvic organs/tissues were determined over time. The following results were obtained: 1. Serum concentrations of FMOX after intravenous infusion showed the peak value of 92.86 +/- 17.05 micrograms/ml at the end of infusion and then gradually decreased to 29.00 +/- 10.49 micrograms/ml in 1 hour and 1.16 +/- 1.08 micrograms/ml in 6 hours. 2. Concentrations in pelvic dead space exudate, which were 6.54 +/- 3.21 micrograms/ml at the end of intravenous infusion, gradually increased to 31.28 +/- 12.69 micrograms/ml in 30 minutes, and the peak of 35.21 +/- 13.29 micrograms/ml in 1 hour. Exudate concentrations gradually decreased to 11.10 +/- 6.64 micrograms/ml at 6 hours after infusion. 3. The serum concentration at the ligature of uterine artery was 103.21 +/- 51.69 micrograms/ml. Among concentrations in pelvic organ/tissues 37.17 +/- 18.20 micrograms/ml in uterine cervix was the highest, followed by 35.77 +/- 7.68 micrograms/g in portio vaginalis, 26.35 +/- 14.15 micrograms/g in tube, 21.62 +/- 12.15 micrograms/g in ovary, 20.56 +/- 9.82 micrograms/g in myometrium, and 16.45 +/- 8.10 micrograms/g in endometrium, in this order. 4. From an analysis of the two-compartment model, the maximum serum concentration was 92.81 micrograms/ml, which was very high. The time of 50% reduction of concentration in beta phase was 1.21 hours. In the pelvic dead space exudate, the maximum concentration was 32.38 micrograms/ml and the time of 50% reduction was 2.44 hours. The AUC was 147 micrograms.hr/ml in serum and 201 micrograms.hr/ml in the pelvic dead space. The shift to the pelvic dead space was 137% when AUC's were used as the basis of the comparison. 5. Clinically, FMOX was excellently effective against adnexitis caused by Peptostreptococcus asaccharolyticus

  4. Mercury concentrations in seabird tissues from Machias Seal Island, New Brunswick, Canada

    Energy Technology Data Exchange (ETDEWEB)

    Bond, Alexander L., E-mail: abond@mun.ca [Atlantic Cooperative Wildlife Ecology Research Network, University of New Brunswick, PO Box 4400, Fredericton, New Brunswick, E3B 5A3 (Canada); Department of Biology, University of New Brunswick, PO Box 4400, Fredericton, New Brunswick, E3B 5A3 (Canada); Diamond, Antony W. [Atlantic Cooperative Wildlife Ecology Research Network, University of New Brunswick, PO Box 4400, Fredericton, New Brunswick, E3B 5A3 (Canada); Department of Biology, University of New Brunswick, PO Box 4400, Fredericton, New Brunswick, E3B 5A3 (Canada)

    2009-07-01

    Mercury is a pervasive environmental contaminant, the anthropogenic portion of which is increasing globally, and in northeastern North America in particular. Seabirds frequently are used as indicators of the marine environment, including mercury contamination. We analysed paired samples for total mercury (Hg) concentrations in feathers and blood from adult and chick, albumen, and lipid-free yolk of seven seabirds breeding on Machias Seal Island, New Brunswick, Canada - Arctic Tern (Sterna paradisaea), Atlantic Puffin (Fratercula arctica), Common Eider (Somateria mollissima), Common Murre (Uria aalge), Common Tern (Sterna hirundo), Leach's Storm-petrel (Oceanodroma leucorhoa), and Razorbill (Alca torda). We also used stable-isotope ratios of carbon ({delta}{sup 13}C), and nitrogen ({delta}{sup 15}N) to evaluate the relationship between carbon source and trophic position and mercury. We found high Hg concentrations across tissue types in Leach's Storm-petrels, and Razorbills, with lower concentrations in other species, the lowest being in Common Eiders. Storm-petrels prey on mesopelagic fish that accumulate mercury, and Razorbills feed on larger, older fish that bioaccumulate heavy metals. Biomagnification of Hg, or the increase in Hg concentration with trophic position as measured by {delta}{sup 15}N, was significant and greater in albumen than other tissues, whereas in other tissues, {delta}{sup 15}N explained little of the overall variation in Hg concentration. Hg concentrations in egg components are higher on Machias Seal Island than other sites globally and in the Gulf of Maine region, but only for some species. Further detailed investigations are required to determine the cause of this trend.

  5. Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications

    OpenAIRE

    Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid C.; Langer, Robert

    2010-01-01

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future.

  6. Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications

    Science.gov (United States)

    Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid C.; Langer, Robert

    2010-01-01

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future. PMID:20726522

  7. Nanotechnology in drug delivery and tissue engineering: from discovery to applications.

    Science.gov (United States)

    Shi, Jinjun; Votruba, Alexander R; Farokhzad, Omid C; Langer, Robert

    2010-09-08

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine, drug delivery and tissue engineering, highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future.

  8. Medical applications of membranes: Drug delivery, artificial organs and tissue engineering

    NARCIS (Netherlands)

    Stamatialis, Dimitrios; Papenburg, B.J.; Girones nogue, Miriam; Saiful, S.; Bettahalli Narasimha, M.S.; Schmitmeier, Stephanie; Wessling, Matthias

    2008-01-01

    This paper covers the main medical applications of artificial membranes. Specific attention is given to drug delivery systems, artificial organs and tissue engineering which seem to dominate the interest of the membrane community this period. In all cases, the materials, methods and the current

  9. In vivo drug release behavior and osseointegration of a doxorubicin-loaded tissue-engineered scaffold

    DEFF Research Database (Denmark)

    Sun, Ming; Chen, Muwan; Wang, Miao

    2016-01-01

    Bone tissue-engineered scaffolds with therapeutic effects must meet the basic requirements as to support bone healing at the defect side and to release an effect drug within the therapeutic window. Here, a rapid prototyped PCL scaffold embedded with chitosan/nanoclay/β-tricalcium phosphate...

  10. Can fluconazole concentrations in saliva be used for therapeutic drug monitoring?

    NARCIS (Netherlands)

    Koks, C. H.; Crommentuyn, K. M.; Hoetelmans, R. M.; Mathôt, R. A.; Beijnen, J. H.

    2001-01-01

    The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state

  11. A method for tissue extraction and determination of prostate concentrations of endogenous androgens by radioimmunoassay

    International Nuclear Information System (INIS)

    Albert, J.; Geller, J.; Geller, S.; Lopez, D.

    1976-01-01

    A method for simultaneously determining concentrations of major androgens in prostate has been developed. Extraction techniques used to isolate the androgens from minced tissue include homogenization with high-speed blades in Delsal's solvent mixture, adsorption to silica gel, followed by column and one thin-layer chromatography (TLC). Radioimmunoassays (RIA) of small aliquots of TLC eluates are used to quantitate picogram amounts of 5α-dihydrotestosterone (DHT) and 5α-androstanediols (Diol) and to estimate testosterone (T) and androstenedione (Ad). Contamination of blanks was reduced to RIA sensitivity limits primarily by treatment of glassware in a self-cleaning oven. The specificity of the method for each androgen was established by TLC separations of known prostate metabolites, antisera specificities, and parallelism of sample aliquots to androgen RIA standards. The overall precision, in terms of coefficients of variation, was 21% for DHT and 24% for Diol. T and Ad could not be measured with acceptable precision because their very low concentrations in prostate (<=0.5 ng/g tissue) were less than RIA sensitivity limits. Accuracy studies indicated recoveries ranging from 96% for Diol to 121% for DHT. In human benign hypertrophic prostate tissue, DHT averaged 153 ng/g soluble protein (5.8 ng/g tissue) which was 17 times higher than values obtained in human spleen and kidney; Diol in prostate showed no consistent differences from values noted in kidney or spleen

  12. Analysis of elemental concentration censored distributions in breast malignant and breast benign neoplasm tissues

    International Nuclear Information System (INIS)

    Kubala-Kukus, A.; Banas, D.; Braziewicz, J.; Gozdz, S.; Majewska, U.; Pajek, M.

    2007-01-01

    The total reflection X-ray fluorescence method was applied to study the trace element concentrations in human breast malignant and breast benign neoplasm tissues taken from the women who were patients of Holycross Cancer Centre in Kielce (Poland). These investigations were mainly focused on the development of new possibilities of cancer diagnosis and therapy monitoring. This systematic comparative study was based on relatively large (∼ 100) population studied, namely 26 samples of breast malignant and 68 samples of breast benign neoplasm tissues. The concentrations, being in the range from a few ppb to 0.1%, were determined for thirteen elements (from P to Pb). The results were carefully analysed to investigate the concentration distribution of trace elements in the studied samples. The measurements of concentration of trace elements by total reflection X-ray fluorescence were limited, however, by the detection limit of the method. It was observed that for more than 50% of elements determined, the concentrations were not measured in all samples. These incomplete measurements were treated within the statistical concept called left-random censoring and for the estimation of the mean value and median of censored concentration distributions, the Kaplan-Meier estimator was used. For comparison of concentrations in two populations, the log-rank test was applied, which allows to compare the censored total reflection X-ray fluorescence data. Found statistically significant differences are discussed in more details. It is noted that described data analysis procedures should be the standard tool to analyze the censored concentrations of trace elements analysed by X-ray fluorescence methods

  13. Pesticide concentrations in frog tissue and wetland habitats in a landscape dominated by agriculture.

    Science.gov (United States)

    Smalling, Kelly L; Reeves, Rebecca; Muths, Erin; Vandever, Mark; Battaglin, William A; Hladik, Michelle L; Pierce, Clay L

    2015-01-01

    Habitat loss and exposure to pesticides are likely primary factors contributing to amphibian decline in agricultural landscapes. Conservation efforts have attempted to restore wetlands lost through landscape modifications to reduce contaminant loads in surface waters and providing quality habitat to wildlife. The benefits of this increased wetland area, perhaps especially for amphibians, may be negated if habitat quality is insufficient to support persistent populations. We examined the presence of pesticides and nutrients in water and sediment as indicators of habitat quality and assessed the bioaccumulation of pesticides in the tissue of two native amphibian species Pseudacris maculata (chorus frogs) and Lithobates pipiens (leopard frogs) at six wetlands (3 restored and 3 reference) in Iowa, USA. Restored wetlands are positioned on the landscape to receive subsurface tile drainage water while reference wetlands receive water from overland run-off and shallow groundwater sources. Concentrations of the pesticides frequently detected in water and sediment samples were not different between wetland types. The median concentration of atrazine in surface water was 0.2 μg/L. Reproductive abnormalities in leopard frogs have been observed in other studies at these concentrations. Nutrient concentrations were higher in the restored wetlands but lower than concentrations thought lethal to frogs. Complex mixtures of pesticides including up to 8 fungicides, some previously unreported in tissue, were detected with concentrations ranging from 0.08 to 1,500 μg/kg wet weight. No significant differences in pesticide concentrations were observed between species, although concentrations tended to be higher in leopard frogs compared to chorus frogs, possibly because of differences in life histories. Our results provide information on habitat quality in restored wetlands that will assist state and federal agencies, landowners, and resource managers in identifying and implementing

  14. Mercury Concentration in the Tissue of Terrestrial Arthropods from the Central California Coast

    Science.gov (United States)

    Ortiz, C.; Weiss-Penzias, P. S.; Flegal, A. R.

    2012-12-01

    The primary goal of this project was to obtain a baseline understanding and investigate the concentration of mercury (Hg) in the tissue of arthropods in coastal California. This region receives significant input of fog which may contain enhanced levels of Hg. Currently there is a lack of data on Hg concentration in the tissue of arthropods (Insecta, Malacostraca, and Arachnida). The sample collection sites were Elkhorn Slough Estuarine Reserve in Moss Landing, and the University of California Santa Cruz (UCSC) campus. Samples collected between February and March, 2012 had total Hg (HgT) concentrations in dry weight that ranged from 27 - 39 ng/g in the Jerusalem cricket (Orthoptera Stenopelmatidae); 80 - 110 ng/g in the camel cricket (Orthoptera Rhaphidophoridae); 21 - 219 ng/g in the ground beetle (Coleoptera Carabidae); 100 - 228 ng/g in the pill bug (Isopoda Armadillidiidae); and 285 - 423 ng/g in the wolf spider (Araneae Lycosidae). Monomethyl mercury (MMHg) concentrations in dry weight were determine to be 4.3 -28.2 ng/g for the ground beetle; 45.5 - 87.8 ng/g for the pill bug, and 252.3 - 293.7 ng/g for the wolf spider. Samples collected in July, 2012 had HgT concentrations in dry weight that ranged from 110 - 168 ng/g in the camel cricket; 337 - 562 ng/g in the ground beetle; 25 - 227 ng/g in the pill bug; and 228 - 501 ng/g in the wolf spider. The preliminary data revealed an 18% increase in the concentration of HgT for wolf spiders, and a 146% increase for ground beetles in the summer when compared to those concentrations measured in the spring. It is hypothesized that coastal fog may be a contributor to this increase of Hg concentration in coastal California arthropods.

  15. Pesticide concentrations in frog tissue and wetland habitats in alandscape dominated by agriculture

    Science.gov (United States)

    Smalling, Kelly L.; Reeves, Rebecca; Muths, Erin L.; Vandever, Mark W.; Battaglin, William A.; Hladik, Michelle; Pierce, Clay L.

    2015-01-01

    Habitat loss and exposure to pesticides are likely primary factors contributing to amphibian decline in agricultural landscapes. Conservation efforts have attempted to restore wetlands lost through landscape modifications to reduce contaminant loads in surface waters and providing quality habitat to wildlife. The benefits of this increased wetland area, perhaps especially for amphibians, may be negated if habitat quality is insufficient to support persistent populations. We examined the presence of pesticides and nutrients in water and sediment as indicators of habitat quality and assessed the bioaccumulation of pesticides in the tissue of two native amphibian species Pseudacris maculata (chorus frogs) and Lithobates pipiens (leopard frogs) at six wetlands (3 restored and 3 reference) in Iowa, USA. Restored wetlands are positioned on the landscape to receive subsurface tile drainage water while reference wetlands receive water from overland run-off and shallow groundwater sources. Concentrations of the pesticides frequently detected in water and sediment samples were not different between wetland types. The median concentration of atrazine in surface water was 0.2 μg/L. Reproductive abnormalities in leopard frogs have been observed in other studies at these concentrations. Nutrient concentrations were higher in the restored wetlands but lower than concentrations thought lethal to frogs. Complex mixtures of pesticides including up to 8 fungicides, some previously unreported in tissue, were detected with concentrations ranging from 0.08 to 1500 μg/kg wet weight. No significant differences in pesticide concentrations were observed between species, although concentrations tended to be higher in leopard frogs compared to chorus frogs, possibly because of differences in life histories. Our results provide information on habitat quality in restored wetlands that will assist state and federal agencies, landowners, and resource managers in identifying and

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

    OpenAIRE

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

    2014-01-01

    Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigat...

  17. Stem cells in drug discovery, tissue engineering, and regenerative medicine: emerging opportunities and challenges.

    Science.gov (United States)

    Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta

    2009-08-01

    Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.

  18. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs

    DEFF Research Database (Denmark)

    Prahl, Julie B; Johansen, Isik S; Cohen, Arieh S

    2014-01-01

    OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6......-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed...... failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid...

  19. An analytical model for nanoparticles concentration resulting from infusion into poroelastic brain tissue.

    Science.gov (United States)

    Pizzichelli, G; Di Michele, F; Sinibaldi, E

    2016-02-01

    We consider the infusion of a diluted suspension of nanoparticles (NPs) into poroelastic brain tissue, in view of relevant biomedical applications such as intratumoral thermotherapy. Indeed, the high impact of the related pathologies motivates the development of advanced therapeutic approaches, whose design also benefits from theoretical models. This study provides an analytical expression for the time-dependent NPs concentration during the infusion into poroelastic brain tissue, which also accounts for particle binding onto cells (by recalling relevant results from the colloid filtration theory). Our model is computationally inexpensive and, compared to fully numerical approaches, permits to explicitly elucidate the role of the involved physical aspects (tissue poroelasticity, infusion parameters, NPs physico-chemical properties, NP-tissue interactions underlying binding). We also present illustrative results based on parameters taken from the literature, by considering clinically relevant ranges for the infusion parameters. Moreover, we thoroughly assess the model working assumptions besides discussing its limitations. While not laying any claims of generality, our model can be used to support the development of more ambitious numerical approaches, towards the preliminary design of novel therapies based on NPs infusion into brain tissue. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Influence of Concentration and Agitation of Sodium Hypochlorite and Peracetic Acid Solutions on Tissue Dissolution.

    Science.gov (United States)

    Tanomaru-Filho, Mário; Silveira, Bruna Ramos Franco; Martelo, Roberta Bosso; Guerreiro-Tanomaru, Juliane Maria

    2015-11-01

    To evaluated the tissue dissolution of sodium hypochlorite (NaOCl) and peracetic acid (PA) solutions at different concentrations, with or without ultrasonic agitation. The following solutions were analyzed: 2.5% NaOCl, 0.5, 1 and 2% PA, 1% PA associated with 6.5% hydrogen peroxide (HP) and saline. Fragments of bovine pulp tissue with 25 ± 2g mg were immersed into test tubes containing 4 mL of the solutions for 10 minutes. In the groups with agitation, pulp tissues were submitted to 2 cycles of 1 minute of ultrasonic agitation. The specimens were weighed after the removal from the solutions. The percentage of mass loss was calculated according to the difference of mass before and after exposure to solutions. Data were submitted to ANOVA and Tukey tests (p Peracetic acid solution has pulp tissue dissolution. However, this ability is lower than 2.5% NaOCl solution. The sodium hypochlorite solution shows higher ability to dissolve tissue than PA.

  1. Mathematical modeling of degradation for bulk-erosive polymers: applications in tissue engineering scaffolds and drug delivery systems.

    Science.gov (United States)

    Chen, Yuhang; Zhou, Shiwei; Li, Qing

    2011-03-01

    The degradation of polymeric biomaterials, which are widely exploited in tissue engineering and drug delivery systems, has drawn significant attention in recent years. This paper aims to develop a mathematical model that combines stochastic hydrolysis and mass transport to simulate the polymeric degradation and erosion process. The hydrolysis reaction is modeled in a discrete fashion by a fundamental stochastic process and an additional autocatalytic effect induced by the local carboxylic acid concentration in terms of the continuous diffusion equation. Illustrative examples of microparticles and tissue scaffolds demonstrate the applicability of the model. It is found that diffusive transport plays a critical role in determining the degradation pathway, whilst autocatalysis makes the degradation size dependent. The modeling results show good agreement with experimental data in the literature, in which the hydrolysis rate, polymer architecture and matrix size actually work together to determine the characteristics of the degradation and erosion processes of bulk-erosive polymer devices. The proposed degradation model exhibits great potential for the design optimization of drug carriers and tissue scaffolds. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. [Application of ultrasound-enhanced gene and drug delivery to the ocular tissue].

    Science.gov (United States)

    Sonoda, Shozo; Yamashita, Toshifumi; Suzuki, Ryo; Maruyama, Kazuo; Sakamoto, Taiji

    2013-01-01

    Visual images provide an immensely rich source of information about the external world. Eye has characteristic structure sensory cells are arranged along the eye wall, and is filled inside with vitreous body. In recent years, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent had widely spread, and numerous number of patients who suffered ocular angiogenic disease such as diabetic retinopathy, age-related macular degeneration and retinal vascular occlusion for the disease, were treated and spared the blindness. Vitreous cavity was regarded as reservoir of drug, intravitreal injection is thought a sort of drug delivery. However, with regard to the administration of a selective drug deliver, it has not yet been solved. Our aim is to establish a new method of gene transfer, drug delivery using low-energy ultrasound to the eye, to date, we confirmed drug and gene deliver to the ocular tissue such as cornea, conjunctiva and retina with high efficiency. In addition, tissue damage was minimal. We have also shown that ultrasound irradiation with combination of a microbubbles or bubble liposome could be introduced drug and gene more effectively. Based on these knowledge, we will focus on development of a new device for intraocular ultrasound exposure and potential for therapeutic application of ultrasound to humans retinal disease such as retinal artery obstruction.

  3. An introduction to predictive modelling of drug concentration in anaesthesia monitors.

    Science.gov (United States)

    DeCou, J; Johnson, K

    2017-01-01

    A significant amount of anaesthetists' work involves the prediction of drug effects and interactions to produce a smooth general anaesthetic that minimises drug side effects and promotes rapid emergence. Successfully managing this process requires a basic understanding of drug effects, experience and inevitably some guesswork, since it is difficult (and in some cases impossible) to anticipate all relevant patient and surgical factors. Although data are generally available to allow calculation of plasma drug and effect site concentrations, this is often difficult to apply in complex clinical contexts, particularly when multiple drug types are used. In recent years, manufacturers have developed and incorporated into anaesthetic workstations technologies that use drug pharmacodynamic and pharmacokinetic data to predict drug effects and interactions. Such systems can predict the duration and effects of drugs during anaesthesia and assist the anaesthetist to understand complex drug interactions. With this information available, different drug types, doses and combinations may be tailored in a scientific way to maximise useful effects whilst minimising overdose and side-effects, particularly in high-risk patients. Examples are used to illustrate how such systems can be used in practice, and how drug effects and interactions can be simulated to "rehearse" an anaesthetic before any drugs are actually administered. At present only a small number of anaesthetic workstations use this technology, and as yet they are not able to manage all drugs used in anaesthetic practice. However, such systems have the potential to help anaesthetists manage the complexity of their work, and to provide information on predicted drug effects in a way that is useful and relevant to both experienced anaesthetists and trainees. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  4. Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges.

    Science.gov (United States)

    Meloni, Monica; Corti, Natascia; Müller, Daniel; Henning, Lars; Gutteck, Ursula; von Braun, Amrei; Weber, Rainer; Fehr, Jan

    2015-01-01

    Therapeutic target serum concentrations of first-line antituberculosis drugs have not been well defined in clinical studies in tuberculosis (TB) patients. We retrospectively investigated the estimated maximum serum concentrations (eC max) of antituberculosis drugs and clinical outcome of TB patients with therapeutic drug monitoring performed between 2010-2012 at our institution, and follow-up until March 2014. The eC max was defined as the highest serum concentration during a sampling period (2, 4 and 6 hours after drug ingestion). We compared the results with published eC max values, and categorised them as either "within reference range", "low eC max", or "very low eC max".Low/very low eC max-levels were defined as follows: isoniazid 2-3/max levels were classified as "low" or "very low". The eC max was below the relevant reference range in 80% of isoniazid, 95% of rifampicin, 30% of pyrazinamide, and 30% of ethambutol measurements. All but one patient were cured of tuberculosis. Although many antituberculosis drug serum concentrations were below the widely used reference ranges, 16 of 17 patients were cured of tuberculosis. These results challenge the use of the published reference ranges for therapeutic drug monitoring.

  5. Absolute quantitative autoradiography of low concentrations of [125I]-labeled proteins in arterial tissue

    International Nuclear Information System (INIS)

    Schnitzer, J.J.; Morrel, E.M.; Colton, C.K.; Smith, K.A.; Stemerman, M.B.

    1987-01-01

    We developed a method for absolute quantitative autoradiographic measurement of very low concentrations of [ 125 I]-labeled proteins in arterial tissue using Kodak NTB-2 nuclear emulsion. A precise linear relationship between measured silver grain density and isotope concentration was obtained with uniformly labeled standard sources composed of epoxy-embedded gelatin containing glutaraldehyde-fixed [ 125 I]-albumin. For up to 308-day exposures of 1 micron-thick tissue sections, background grain densities ranged from about two to eight grains/1000 micron 2, and the technique was sensitive to as little as about one grain/1000 micron 2 above background, which correspond to a radioactivity concentration of about 2 x 10(4) cpm/ml. A detailed statistical analysis of variability was performed and the sum of all sources of variation quantified. The half distance for spatial resolution was 1.7 micron. Both visual and automated techniques were employed for quantitative grain density analysis. The method was illustrated by measurement of in vivo transmural [ 125 I]-low-density lipoprotein [( 125 I]-LDL) concentration profiles in de-endothelialized rabbit thoracic aortic wall

  6. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

    Directory of Open Access Journals (Sweden)

    David R Lionberger

    2010-11-01

    Full Text Available David R Lionberger1, Michael J Brennan21Southwest Orthopedic Group, Houston, TX, USA; 2Department of Medicine, Bridgeport Hospital, Bridgeport, CT, USAAbstract: The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs, diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9. In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs. The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions

  7. Hypnosis control based on the minimum concentration of anesthetic drug for maintaining appropriate hypnosis.

    Science.gov (United States)

    Furutani, Eiko; Nishigaki, Yuki; Kanda, Chiaki; Takeda, Toshihiro; Shirakami, Gotaro

    2013-01-01

    This paper proposes a novel hypnosis control method using Auditory Evoked Potential Index (aepEX) as a hypnosis index. In order to avoid side effects of an anesthetic drug, it is desirable to reduce the amount of an anesthetic drug during surgery. For this purpose many studies of hypnosis control systems have been done. Most of them use Bispectral Index (BIS), another hypnosis index, but it has problems of dependence on anesthetic drugs and nonsmooth change near some particular values. On the other hand, aepEX has an ability of clear distinction between patient consciousness and unconsciousness and independence of anesthetic drugs. The control method proposed in this paper consists of two elements: estimating the minimum effect-site concentration for maintaining appropriate hypnosis and adjusting infusion rate of an anesthetic drug, propofol, using model predictive control. The minimum effect-site concentration is estimated utilizing the property of aepEX pharmacodynamics. The infusion rate of propofol is adjusted so that effect-site concentration of propofol may be kept near and always above the minimum effect-site concentration. Simulation results of hypnosis control using the proposed method show that the minimum concentration can be estimated appropriately and that the proposed control method can maintain hypnosis adequately and reduce the total infusion amount of propofol.

  8. Postmortem Fluid and Tissue Concentrations of THC, 11-OH-THC and THC-COOH.

    Science.gov (United States)

    Saenz, Sunday R; Lewis, Russell J; Angier, Mike K; Wagner, Jarrad R

    2017-07-01

    Marijuana is the most commonly abused illicit drug worldwide. Marijuana is used for its euphoric and relaxing properties. However, marijuana use has been shown to result in impaired memory, cognitive skills and psychomotor function. The Federal Aviation Administration's Civil Aerospace Medical Institute conducts toxicological analysis on aviation fatalities. Due to severe trauma associated with aviation accidents, blood is not always available; therefore, the laboratory must rely on specimens other than blood for toxicological analysis in ~30-40% of cases. However, the postmortem distribution of cannabinoids has not been well characterized. The purpose of this research is to evaluate the distribution of Δ9-tetrahydrocannabinol (THC), and its metabolites, 11-hydroxy-tetrahydrocannabinol (11-OH-THC) and THC-COOH, in postmortem fluid and tissue specimens from 11 fatal aviation accident cases (2014-2015) previously found positive for cannabinoids. Specimens evaluated, when available, included: blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, brain, heart and bile. We developed and validated (following SWGTOX guidelines) a sensitive and robust method using solid-phase extraction and liquid chromatography-tandem mass spectrometry to identify and quantify THC, 11-OH-THC and THC-COOH in postmortem fluids and tissues. The method readily identified and quantified these cannabinoids in postmortem fluids and tissues below 1 ng/mL. Qualitative cannabinoid results within each case were comparable between blood and non-blood specimens. However, there was no consistent distribution of the cannabinoids between blood and any other fluids or tissues. Therefore, while quantitative interpretation of non-blood postmortem fluid and tissues samples is not prudent, a majority of the non-blood specimens tested could be suitable alternative/supplemental choices for qualitative cannabinoid detection. Published by Oxford University Press 2017. This work is written by (a) US

  9. Concentrations of uranium and thorium isotopes in uranium millers' and miners' tissues

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Singh, N.P.; Paschoa, A.S.; Lloyd, R.D.; Saccomanno, G.

    1985-09-01

    The alpha-emitting isotopes of uranium and thorium were determined in the lungs of 14 former uranium miners and in soft tissues and bones of three miners and two millers. These radionuclides were also determined in soft tissues and bones of seven normal controls. The average concentrations in pCi/kg wet weight in 17 former miners' lungs are as follows: 238 U, 75; 234 U, 80; 230 Th, 79. Concentrations of each nuclide ranged from 2 to 325 pCi/kg. The average ratio of 238 U/ 234 U was 0.92, ranging from 0.64 to 1.06. The mean ratio of 230 Th/ 234 U was 1.04, ranging from 0.33 to 3.54. The near equilibrium between 230 Th and /sup 238,234/U indicates that the rate of elimination of uranium and thorium from lungs is the same in former uranium miners. The concentrations of 234 U and 238 U were highest in lung; however, the concentration of 230 Th in bones was either higher than or comparable to its concentration in lung. The concentration ratios of 230 Th/ 234 U in bone of uranium miners and millers measured in our laboratory have been compared with results predicted by ICRP-30 metabolic models. These results indicate that the ICRP metabolic models for thorium and uranium were only marginally successful in predicting the ratio of 230 Th/ 234 U in bones, and that effective release rate of uranium from skeleton may be more rapid than predicted by the ICRP model. 9 figs., 21 tabs

  10. Changes in Lecithin Concentration in the Human Brain Tissue in Some Neurodegenerative Conditions

    International Nuclear Information System (INIS)

    Ajanovic, A.; Mihaljevic, M.; Hasanbasic, D.; Rukavina, D.; Sofic, E.

    2011-01-01

    As a consequence of a possible increase in oxidative stress or deterioration of nerve cells during aging, in some states neurodegeneration was demonstrated by multiple biochemical deficiency, especially deficiency of cholesterol and lecithin in brain regions. The aim of this study was to determine the changes in the concentration of lecithin in different regions of brain tissue (MC - motor cortex, NC - nucleus caudates, GT - temporal gyrus) dissected postmortem from people with senile dementia of Alzheimer's type (SDAT), and persons with Parkinson's disease (PD) as compared to people who died without these diseases (C). Spectrophotometric determination of lecithin in 18 postmortem brain tissue regions collected from of 12 persons with SDAT, in 11 postmortem brain tissue regions of 8 persons with PD and in 18 postmortem brain tissue regions of 8 control persons, was performed by enzymatic method. The content of lecithin in MC: 14.4 mg/g fresh tissue (f.t.) and GT: 13.1 mg/g (f.t.) for SDAT was significantly reduced (p < 0.01) by about 30 %, compared to control where there was: 21.6 mg/g (f.t.) in MC and 18.3 mg/g (f.t.) in the GT estimated. In all regions of the brain of PD patients, the content of lecithin was decreased by about 12 % compared to control, but without statistical significance. These results suggest that changes in the content of lecithin in these regions of brain tissue might affect the changes in the membrane potential and cell degeneration. (author)

  11. The occurence of nitrofuran metabolites in the tissues of chickens exposed to very low dietary concentration in the nitrofurans

    NARCIS (Netherlands)

    McCracken, R.J.; Rhijn, van J.A.; Kennedy, D.G.

    2005-01-01

    The global problem of food products contaminated by residues of the banned carcinogenic nitrofuran drugs has prompted research into how such residues accumulate in tissues. In the study described here, two aspects have been investigated where the nitrofurans accumulate in tissues from chickens

  12. 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

    Directory of Open Access Journals (Sweden)

    Michaela Thomas

    2017-11-01

    Full Text Available Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone, and poly(ethylene glycol. This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

  13. [Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier].

    Science.gov (United States)

    Kubo, Yoshiyuki

    2015-01-01

    Studies of neurological dysfunction have revealed the neuroprotective effect of several cationic drugs, suggesting their usefulness in the treatment of neurological diseases. In the brain and retina, blood-tissue barriers such as blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict nonspecific solute transport between the circulating blood and neural tissues. Therefore study of cationic drug transport at these barriers is essential to achieve systemic delivery of neuroprotective agents into the neural tissues. In the retina, severe diseases such as diabetic retinopathy and macular degeneration can cause neurological dysfunction that dramatically affects patients' QOL. The BRB is formed by retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB). Blood-to-retina transport of cationic drugs was investigated at the inner BRB, which is known to nourish two thirds of the retina. Blood-to-retinal transport of verapamil suggested that the barrier function of the BRB differs from that of the BBB. Moreover, carrier-mediated transport of verapamil and pyrilamine revealed the involvement of novel organic cation transporters at the inner BRB. The identified transport systems for cationic drugs are sensitive to several cationic neuroprotective and anti-angiogenic agents such as clonidine and propranolol, and the involvement of novel transporters was also suggested in their blood-to-retina transport across the inner BRB.

  14. Tissue-specific concentrations and patterns of perfluoroalkyl carboxylates and sulfonates in East Greenland polar bears.

    Science.gov (United States)

    Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune; Born, Erik W

    2012-11-06

    Several perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs) of varying chain length are bioaccumulative in biota. However, wildlife reports have focused on liver and with very little examination of other tissues, and thus there is a limited understanding of their distribution and potential effects in the mammalian body. In the present study, the comparative accumulation of C(6) to C(15) PFCAs, C(4), C(6), C(8) and C(10) PFSAs, and select precursors were examined in the liver, blood, muscle, adipose, and brain of 20 polar bears (Ursus maritimus) from Scoresby Sound, Central East Greenland. Overall, PFSA and PFCA concentrations were highest in liver followed by blood > brain > muscle ≈ adipose. Liver and blood samples contained proportionally more of the shorter/medium chain length (C(6) to C(11)) PFCAs, whereas adipose and brain samples were dominated by longer chain (C(13) to C(15)) PFCAs. PFCAs with lower lipophilicities accumulated more in the liver, whereas the brain accumulated PFCAs with higher lipophilicities. The concentration ratios (±SE) between perfluorooctane sulfonate and its precursor perfluorooctane sulfonamide varied among tissues from 9 (±1):1 (muscle) to 36 (±7):1 (liver). PFCA and PFSA patterns in polar bears indicate that the pharmacokinetics of these compounds are to some extent tissue-specific, and are the result of several factors that may include differing protein interactions throughout the body.

  15. Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

    DEFF Research Database (Denmark)

    Chen, Muwan; Le, Dang Q S; Hein, San

    2012-01-01

    Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone......, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount...... of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug....

  16. Evaluation of a method for determining concentrations of isoeugenol, an AQUI-S residue, in fillet tissue from freshwater fish species.

    Science.gov (United States)

    Meinertz, Jeffery R; Schreier, Theresa M; Bernardy, Jeffry A

    2008-01-01

    AQUI-S is a fish anesthetic/sedative that is approved for use in a number of countries throughout the world and has the potential for use in the United States. The active ingredient in AQUI-S is isoeugenol. A method for determining isoeugenol concentrations in edible fillet tissue is needed for regulatory purposes, including surveillance and potential use in studies fulfilling human food safety data requirements if U.S. Food and Drug Administration approval is pursued. A method was developed and evaluated for determining isoeugenol concentrations in fillet tissue using relatively common procedures and equipment. The method produced accurate and precise results with fillet tissue from 10 freshwater fish species. The percentage of isoeugenol recovered from samples fortified with isoeugenol at nominal concentrations of 1, 50, and 100 microg/g for all species was always >80 and fillet tissue containing biologically incurred isoeugenol was fillet tissue extracts from 9 of the 10 species. The method detection limits for all but one species ranged from 0.004 to 0.014 microg/g, and the quantitation limits ranged from 0.012 to 0.048 microg/g.

  17. Concentration of 17 Elements in Subcellular Fractions of Beef Heart Tissue Determined by Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wester, P O

    1964-12-15

    Subcellular fractions of beef heart tissue are investigated, by means of neutron activation analysis, with respect to their concentration of 17 different elements. A recently developed ion-exchange technique combined with gamma spectrometry is used. The homogeneity of the subcellular fractions is examined electron microscopically. The following elements are determined: As, Ba, Br, Cas Co, Cs, Cu, Fe, Hg, La, Mo, P, Rb, Se, Sm, W and Zn. The determination of Ag, Au, Cd, Ce, Cr, Sb and Sc is omitted, in view of contamination. Reproducible and characteristic patterns of distribution are obtained for all elements studied.

  18. Concentration of 17 Elements in Subcellular Fractions of Beef Heart Tissue Determined by Neutron Activation Analysis

    International Nuclear Information System (INIS)

    Wester, P.O.

    1964-12-01

    Subcellular fractions of beef heart tissue are investigated, by means of neutron activation analysis, with respect to their concentration of 17 different elements. A recently developed ion-exchange technique combined with gamma spectrometry is used. The homogeneity of the subcellular fractions is examined electron microscopically. The following elements are determined: As, Ba, Br, Cas Co, Cs, Cu, Fe, Hg, La, Mo, P, Rb, Se, Sm, W and Zn. The determination of Ag, Au, Cd, Ce, Cr, Sb and Sc is omitted, in view of contamination. Reproducible and characteristic patterns of distribution are obtained for all elements studied

  19. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch.

    Science.gov (United States)

    Lionberger, David R; Brennan, Michael J

    2010-11-10

    The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978-2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5-1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical-chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions.

  20. Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wester, P O

    1964-06-15

    By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected.

  1. Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

    International Nuclear Information System (INIS)

    Wester, P.O.

    1964-06-01

    By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected

  2. Drug injection into fat tissue with a laser based microjet injector

    Science.gov (United States)

    Han, Tae-hee; Hah, Jung-moo; Yoh, Jack J.

    2011-05-01

    We have investigated a new micro drug jet injector using laser pulse energy. An infrared laser beam of high energy (˜3 J/pulse) is focused inside a driving fluid in a small chamber. The pulse then induces various energy releasing processes, and generates fast microjets through a micronozzle. The elastic membrane of this system plays an important role in transferring mechanical pressure and protecting drug from heat release. In this paper, we offer the sequential images of microjet generation taken by a high speed camera as an evidence of the multiple injections via single pulse. Furthermore, we test the proposed system to penetrate soft animal tissues in order to evaluate its feasibility as an advanced transdermal drug delivery method.

  3. Mechanism of erosion of nanostructured porous silicon drug carriers in neoplastic tissues

    Science.gov (United States)

    Tzur-Balter, Adi; Shatsberg, Zohar; Beckerman, Margarita; Segal, Ester; Artzi, Natalie

    2015-01-01

    Nanostructured porous silicon (PSi) is emerging as a promising platform for drug delivery owing to its biocompatibility, degradability and high surface area available for drug loading. The ability to control PSi structure, size and porosity enables programming its in vivo retention, providing tight control over embedded drug release kinetics. In this work, the relationship between the in vitro and in vivo degradation of PSi under (pre)clinically relevant conditions, using breast cancer mouse model, is defined. We show that PSi undergoes enhanced degradation in diseased environment compared with healthy state, owing to the upregulation of reactive oxygen species (ROS) in the tumour vicinity that oxidize the silicon scaffold and catalyse its degradation. We further show that PSi degradation in vitro and in vivo correlates in healthy and diseased states when ROS-free or ROS-containing media are used, respectively. Our work demonstrates that understanding the governing mechanisms associated with specific tissue microenvironment permits predictive material performance. PMID:25670235

  4. Radionuclide concentrations in bird tissues, their foods and feeding areas near Ravenglass

    International Nuclear Information System (INIS)

    Lowe, V.P.W.

    1987-08-01

    Since 1983, concern has been expressed about an apparent decline in the numbers of waterfowl, waders and gulls in the Ravenglass estuary, particularly of the black-headed gulls nesting on the Drigg dunes; it was suggested this might be due to the radionuclide concentrations in their diet and general environment. Oystercatchers and shelduck had some of the highest concentrations of Cs-137 in their tissues, yet their breeding and numbers remained unaffected. Calculations of the total dose equivalent to the whole body of gulls spending 4 months in the estuary before laying eggs, amounted to 2.8 mSv (≅ 2.4 m Gy), and to the gut lining 40.3 mSv. As a minimum chronic dose of 1000 m Gy d -1 has been found to be necessary to retard the growth of chicks or cause 50% mortality among gull chick embryos before full development, radionuclide concentrations at Ravenglass were at least three orders of magnitude too low to have any effect. 12 species of marine invertebrates were also analysed, but no evidence was found that radionuclides from Sellafield were being accumulated in any species to the point where concentrations were of potential importance to birds feeding on them. (author)

  5. Highly Concentrated Alginate-Gellan Gum Composites for 3D Plotting of Complex Tissue Engineering Scaffolds

    Directory of Open Access Journals (Sweden)

    Ashwini Rahul Akkineni

    2016-04-01

    Full Text Available In tissue engineering, additive manufacturing (AM technologies have brought considerable progress as they allow the fabrication of three-dimensional (3D structures with defined architecture. 3D plotting is a versatile, extrusion-based AM technology suitable for processing a wide range of biomaterials including hydrogels. In this study, composites of highly concentrated alginate and gellan gum were prepared in order to combine the excellent printing properties of alginate with the favorable gelling characteristics of gellan gum. Mixtures of 16.7 wt % alginate and 2 or 3 wt % gellan gum were found applicable for 3D plotting. Characterization of the resulting composite scaffolds revealed an increased stiffness in the wet state (15%–20% higher Young’s modulus and significantly lower volume swelling in cell culture medium compared to pure alginate scaffolds (~10% vs. ~23%. Cytocompatibility experiments with human mesenchymal stem cells (hMSC revealed that cell attachment was improved—the seeding efficiency was ~2.5–3.5 times higher on the composites than on pure alginate. Additionally, the composites were shown to support hMSC proliferation and early osteogenic differentiation. In conclusion, print fidelity of highly concentrated alginate-gellan gum composites was comparable to those of pure alginate; after plotting and crosslinking, the scaffolds possessed improved qualities regarding shape fidelity, mechanical strength, and initial cell attachment making them attractive for tissue engineering applications.

  6. Diclofenac sex-divergent drug-drug interaction with Sunitinib: pharmacokinetics and tissue distribution in male and female mice.

    Science.gov (United States)

    Chew, Chii Chii; Ng, Salby; Chee, Yun Lee; Koo, Teng Wai; Liew, Ming Hui; Chee, Evelyn Li-Ching; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L; Segarra, Ignacio

    2017-08-01

    Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC 0→∞ 38% in plasma (p diclofenac increased the liver uptake efficiency in male (27%, p diclofenac with probable clinical translatability due to potential different effects in male and female patients requiring careful selection of the NSAID and advanced TDM to implement a personalized treatment.

  7. Bioactive Molecule-loaded Drug Delivery Systems to Optimize Bone Tissue Repair.

    Science.gov (United States)

    Oshiro, Joao Augusto; Sato, Mariana Rillo; Scardueli, Cassio Rocha; Lopes de Oliveira, Guilherme Jose Pimentel; Abucafy, Marina Paiva; Chorilli, Marlus

    2017-01-01

    Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. 3D Photo-Fabrication for Tissue Engineering and Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rúben F. Pereira

    2015-03-01

    Full Text Available The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix (ECM on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photo-fabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.

  9. Flexing the PECs: Predicting environmental concentrations of veterinary drugs in Canadian agricultural soils.

    Science.gov (United States)

    Kullik, Sigrun A; Belknap, Andrew M

    2017-03-01

    Veterinary drugs administered to food animals primarily enter ecosystems through the application of livestock waste to agricultural land. Although veterinary drugs are essential for protecting animal health, their entry into the environment may pose a risk for nontarget organisms. A means to predict environmental concentrations of new veterinary drug ingredients in soil is required to assess their environmental fate, distribution, and potential effects. The Canadian predicted environmental concentrations in soil (PECsoil) for new veterinary drug ingredients for use in intensively reared animals is based on the approach currently used by the European Medicines Agency for VICH Phase I environmental assessments. The calculation for the European Medicines Agency PECsoil can be adapted to account for regional animal husbandry and land use practices. Canadian agricultural practices for intensively reared cattle, pigs, and poultry differ substantially from those in the European Union. The development of PECsoil default values and livestock categories representative of typical Canadian animal production methods and nutrient management practices culminates several years of research and an extensive survey and analysis of the scientific literature, Canadian agricultural statistics, national and provincial management recommendations, veterinary product databases, and producers. A PECsoil can be used to rapidly identify new veterinary drugs intended for intensive livestock production that should undergo targeted ecotoxicity and fate testing. The Canadian PECsoil model is readily available, transparent, and requires minimal inputs to generate a screening level environmental assessment for veterinary drugs that can be refined if additional data are available. PECsoil values for a hypothetical veterinary drug dosage regimen are presented and discussed in an international context. Integr Environ Assess Manag 2017;13:331-341. © 2016 Her Majesty the Queen in Right of Canada

  10. Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour

    International Nuclear Information System (INIS)

    Maase, H. van der

    1986-01-01

    The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C 3 H mouse mammary carcinoma in vivo. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP). The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues. (Auth.)

  11. The impact of currently used oral antihyperglycemic drugs on dysfunctional adipose tissue

    Directory of Open Access Journals (Sweden)

    Tomić-Naglić Dragana

    2017-01-01

    Full Text Available Obesity is a disease with pandemic frequency, often accompanied by chronic metabolic and organic complications. Type 2 diabetes mellitus (T2DM is among the most common metabolic complications of obesity. The first step in the treatment of T2DM is medical nutrition therapy combined with moderate physical activity and with advice to patients to reduce their body weight. Pharmacotherapy starts with metformin, and in the case of inadequate therapeutic response, another antihyperglycemic agent should be added. The most clinical experience exists with sulfonylurea agents, but their use is limited due to high incidence of hypoglycemia and increase in body weight. Based on the fact that dysfunction of adipose tissue can lead to the development of chronic degenerative complications, precise use of drugs with a favorable effect on the functionality of adipose tissue represents an imperative of modern T2DM treatment. Antihyperglycemic drugs of choice in obese individuals are those which cause maturation of adipocytes, improvement of secretion of protective adipokines, and redistribution of fat mass from visceral to subcutaneous depots. Oral antihyperglycemic agents that can affect the functionality of adipose tissue are metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and thiazolidinediones.

  12. Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

    Science.gov (United States)

    Nitta, Sachiko Kaihara; Numata, Keiji

    2013-01-01

    There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin). The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed. PMID:23344060

  13. Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Keiji Numata

    2013-01-01

    Full Text Available There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin, protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin. The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed.

  14. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Guarino, Vincenzo, E-mail: vguarino@unina.it; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi [Institute for Polymers, Composites and Biomaterials, Department of Chemical Sciences & Materials Technology, National Research Council of Italy, V.le Kennedy 54, Naples (Italy)

    2015-12-17

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial’s manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell–biomaterial and cell– cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

  15. Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and tissue engineering.

    Science.gov (United States)

    Jiang, Yanjiao; Chen, Jing; Deng, Chao; Suuronen, Erik J; Zhong, Zhiyuan

    2014-06-01

    Hydrogels, microgels and nanogels have emerged as versatile and viable platforms for sustained protein release, targeted drug delivery, and tissue engineering due to excellent biocompatibility, a microporous structure with tunable porosity and pore size, and dimensions spanning from human organs, cells to viruses. In the past decade, remarkable advances in hydrogels, microgels and nanogels have been achieved with click chemistry. It is a most promising strategy to prepare gels with varying dimensions owing to its high reactivity, superb selectivity, and mild reaction conditions. In particular, the recent development of copper-free click chemistry such as strain-promoted azide-alkyne cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click chemistry, and oxime reaction renders it possible to form hydrogels, microgels and nanogels without the use of potentially toxic catalysts or immunogenic enzymes that are commonly required. Notably, unlike other chemical approaches, click chemistry owing to its unique bioorthogonal feature does not interfere with encapsulated bioactives such as living cells, proteins and drugs and furthermore allows versatile preparation of micropatterned biomimetic hydrogels, functional microgels and nanogels. In this review, recent exciting developments in click hydrogels, microgels and nanogels, as well as their biomedical applications such as controlled protein and drug release, tissue engineering, and regenerative medicine are presented and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    International Nuclear Information System (INIS)

    Guarino, Vincenzo; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi

    2015-01-01

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial’s manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell–biomaterial and cell– cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues

  17. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    Science.gov (United States)

    Guarino, Vincenzo; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi

    2015-12-01

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial's manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell-biomaterial and cell- cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

  18. Biaxial testing of canine annulus fibrosus tissue under changing salt concentrations

    Directory of Open Access Journals (Sweden)

    Jacques M. Huyghe

    2010-03-01

    Full Text Available The in vivo mechanics of the annulus fibrosus of the intervertebral disc is one of biaxial rather than uniaxial loading. The material properties of the annulus are intimately linked to the osmolarity in the tissue. This paper presents biaxial relaxation experiments of canine annulus fibrosus tissue under stepwise changes of external salt concentration. The force tracings show that stresses are strongly dependent on time, salt concentration and orientation. The force tracing signature of are sponse to a change instrain, is one of a jumpin stress that relaxes partly as the new strain is maintained. The force tracing signature of a stepwise change in salt concentration is a progressive monotonous change in stress towards a new equilibrium value. Although the number of samples does not allow any definitive quantitative conclusions, the trends may shed light on the complex interaction among the directionality of forces, strains and fiber orientation on one hand, and on the other hand, the osmolarity of the tissue. The dual response to a change in strain is understood as an immediate response before fluid flows in or out of the tissue, followed by a progressive readjustment of the fluid content in time because of the gradient in fluid chemical potential between the tissue and the surrounding solution.A mecânica in vivo do anel fibroso do disco intervertebral é baseada em carregamento biaxial ao invés de uniaxial. As propriedades materiais do anel estão intimamente ligadas à osmolaridade no tecido. O artigo apresenta experimentos de relaxação biaxiais do anel fibroso de um tecido canino sob mudanças abruptas na concentração externa de sal. A assinatura da força devido à mudança brusca de salinidade resulta em uma progressiva e monótona mudança na tensão em direção a um novo valor de equilíbrio. Embora o número de amostras não permita nenhuma conclusão quantitativa, as tendências podem abrir uma luz no entendimento das intera

  19. Validation of NIRS in measuring tissue hemoglobin concentration and oxygen saturation on ex vivo and isolated limb models

    Science.gov (United States)

    Xu, Xiaorong; Zhu, Wen; Padival, Vikram; Xia, Mengna; Cheng, Xuefeng; Bush, Robin; Christenson, Linda; Chan, Tim; Doherty, Tim; Iatridis, Angelo

    2003-07-01

    Photonify"s tissue spectrometer uses Near-Infrared Spectroscopy for real-time, noninvasive measurement of hemoglobin concentration and oxygen saturation [SO2] of biological tissues. The technology was validated by a series of ex vivo and animal studies. In the ex vivo experiment, a close loop blood circulation system was built, precisely controlling the oxygen saturation and the hemoglobin concentration of a liquid phantom. Photonify"s tissue spectrometer was placed on the surface of the liquid phantom for real time measurement and compared with a gas analyzer, considered the gold standard to measure oxygen saturation and hemoglobin concentration. In the animal experiment, the right hind limb of each dog accepted onto the study was surgically removed. The limb was kept viable by connecting the femoral vein and artery to a blood-primed extracorporeal circuit. Different concentrations of hemoglobin were obtained by adding designated amount of saline solution into the perfusion circuit. Photonify"s tissue spectrometers measured oxygen saturation and hemoglobin concentration at various locations on the limb and compared with gas analyzer results. The test results demonstrated that Photonify"s tissue spectrometers were able to detect the relative changes in tissue oxygen saturation and hemoglobin concentration with a high linear correlation compared to the gas analyzer

  20. Dissimilarities in the metabolism of antiretroviral drugs used in HIV pre-exposure prophylaxis in colon and vagina tissues.

    Science.gov (United States)

    To, Elaine E; Hendrix, Craig W; Bumpus, Namandjé N

    2013-10-01

    Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. An in vivo approach for globally estimating the drug flow between blood and tissue for nafamostat mesilate: the main hydrolysis site determination in human.

    Science.gov (United States)

    Cao, Yan-Guang; Chen, Yuan-Cheng; Hao, Kun; Zhang, Ming; Liu, Xiao-Quan

    2008-11-01

    Nafamostat mesilate, an ester drug with extensive hydrolysis in vivo, exhibits species difference in the relative contribution for its hydrolysis in blood and tissues. For the rat, the main hydrolysis site may be blood and human may be tissue (mainly by liver). The paper gave in vivo evidence that human tissue may give more contribution for its hydrolysis. In the initial phase of drug administration, the drug accumulating level in tissue was low; the efflux fraction from tissue into blood can be ignorable comparing with the drug influx into tissue. Based on urine and plasma metabolite analysis, we concluded that in the initial phase almost all the drug hydrolysis in blood was excreted into urine. Then according to the initial urine metabolite analysis, we can estimate the drug hydrolysis rate in blood. The rate of drug diffusion from blood into tissues can be deduced based on the mass balance analysis of the initial blood drug. With the estimated rate constants, the drug efflux from tissues into blood was calculated according to equation: OFT-B (efflux from tissues) = OFB-U (blood hydrolysis fraction)+OFB-T (influx into tissues)-DB (hydrolysis in blood). The net flow (influent flux minus effluent flux) represented the drug hydrolysis fraction in tissue. As the result indicated, in human about 20% drug administrated was hydrolyzed in blood and nearly 80% in tissues. The relative hydrolysis fraction indicated that the main hydrolysis site in human body may locate in tissue, which was different to rats.

  2. Substantial elevation of interleukin-6 concentration in peritendinous tissue, in contrast to muscle, following prolonged exercise in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Olesen, Jens; Gemmer, Carsten

    2002-01-01

    Plasma interleukin-6 (IL-6) concentration has been shown to increase with exercise and various cell types and tissues have been suggested to be responsible for this increase. At present no studies have measured the interstitial concentration of IL-6 in skeletal muscle and connective tissue......, 48 h, 72 h and 96 h post-exercise in both the medial gastrocnemius muscle (not measured at rest due to risk of disabling the subsequent exercise, and 24 h and 72 h post-exercise) and the peritendinous tissue around the Achilles tendon using microdialysis catheters with a high molecular mass cut...

  3. Determination of drug residues by CLAR-MS/MS in animal tissues

    International Nuclear Information System (INIS)

    Brenes Jimenez, Jose Eduardo

    2009-01-01

    Produced food of animal origin, present the possibility of occurrence of any contact with substances that have negative effects on the health of people who consume them. The use of drugs in veterinary medicine is one of the possible sources of such waste; so, the conditions for the analysis of some classes of antibiotics in animal tissues are based on the study. Costa Rica and the countries that are export destination, have regulation and programs for control before to be distributed in local markets, or post if it is received any complaint of pollution. The high resolution liquid chromatography coupled to mass spectrometers (CLAR-MS/MS) allows the analysis of analytes monitored, according to the specifications required by the legislation. The cases of two laboratories in Costa Rica are presented as the only ones who have the ability to perform the analysis of drug residues CLAR-MS/MS. (author) [es

  4. Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies

    Directory of Open Access Journals (Sweden)

    Rishi Raj Rikhi

    2016-03-01

    Full Text Available Limited research exists regarding the most aggressive forms of hepatoblastoma. Cell lines of the rare subtypes of hepatoblastoma with poor prognosis are not only difficult to attain, but are challenging to characterize histologically. A community approach to educating parents and families of the need for donated tissue is necessary for scientists to have access to resources for murine models and drug discovery. Herein we describe the currently available resources, the today’s existing gaps in research, and the path to move forward for uniform cure of hepatoblastoma.

  5. Human engineered heart tissue as a model system for drug testing.

    Science.gov (United States)

    Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

    2016-01-15

    Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles.

    Science.gov (United States)

    Lorenz, T; Bojko, S; Bunjes, H; Dietzel, A

    2018-02-13

    Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented in this paper. A lithographic fabrication sequence was established, allowing fabrication of intersecting and coaxial channels of different depths in glass as is required for 3D flow-focusing. Fenofibrate was used as a model for active pharmaceutical ingredients with very low water solubility in the experiments. It was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow-focusing geometry. In the thread formation regime, the drug solution turned into monodisperse droplets of sizes down to below 1 μm. Fast supersaturation occurs individually in each droplet, as the disperse phase solvent progressively diffuses into the surrounding water. Liquid antisolvent precipitation results in highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can be precisely controlled by the continuous and disperse phase pressure. By comparing optically measured droplet sizes with particle sizes by dynamic light scattering, we could confirm that exactly one particle forms in every droplet. Furthermore, a downstream on-chip concentration allowed withdrawal of major volumes of only the continuous phase fluid which enabled an increase of particle concentration by up to 250 times.

  7. Feeding a high-concentrate corn straw diet induced epigenetic alterations in the mammary tissue of dairy cows.

    Directory of Open Access Journals (Sweden)

    Guozhong Dong

    Full Text Available The objective of this study was to investigate the effects of feeding a high-concentrate corn straw (HCS diet (65% concentrate+35% corn straw on the epigenetic changes in the mammary tissue of dairy cows in comparison with a low-concentrate corn straw (LCS diet (46% concentrate+54% corn straw and with a low-concentrate mixed forage (LMF diet (46% concentrate+54% mixed forage.Multiparous mid-lactation Chinese Holstein cows were fed one of these three diets for 6 weeks, at which time blood samples and mammary tissue samples were collected. Mammary arterial and venous blood samples were analyzed for lipopolysaccharide (LPS concentrations while mammary tissue samples were assayed for histone H3 acetylation and the methylation of specific genes associated with fat and protein synthesis.Extraction of histones and quantification of histone H3 acetylation revealed that acetylation was significantly reduced in cows fed the HCS diet, as compared with cows fed the LCS diet. Cows fed the HCS diet had significantly higher LPS concentrations in the mammary arterial blood, as compared with cows fed the LCS diet. We found that the extent of histone H3 acetylation was negatively correlated with LPS concentrations. The methylation of the stearoyl-coenzyme A desaturase gene associated with milk fat synthesis was increased in cows fed the HCS diet. By contrast, methylation of the gene encoding the signal transducer and activator of transcription 5A was reduced in cows fed the HCS diet, suggesting that feeding a high-concentrate corn straw diet may alter the methylation of specific genes involved in fat and protein synthesis in the mammary tissue of dairy cows.Feeding the high-concentrate diet induced epigenetic changes in the mammary tissues of dairy cows, possibly through effecting the release of differing amounts of LPS into the mammary blood.

  8. Determination of concentration of heavy metals (Pb, Cd, Fe) in animal tissues using atomic absorption spectrometry

    International Nuclear Information System (INIS)

    RAZAFINTSALAMA, V.T.

    2009-01-01

    Heavy metals are classified among the inorganic compounds. The latter type of metal is found in rocks, fertilizers, urban mud but may also originate from the atmospheric pollution. A particular characteristic of heavy metals is their bioaccumulation in the food chain. Therefore, lead and cadmium, which are classified as heavy metals may be easily found in animal products and can lead to food poisoning if their concentrations are higher than the maximum permissible values as requested by international agencies such as the c odex alimentarius . The values are set down and differ according to types of food for human consuption and the trading companies take action accordingly. Therefore, it is necessary to set up a quality control system through analytical laboratory measurements and testings. This study underlies the method of determination of lead, cadmium and iron in animal tissues by atomic absorption spectrometry. The results showed that the method is sensitive and reliable. For each analyte, the Z-score lies between -2 and 2, indicating that the method is working properly. The analytical results showed that: (i) only beef and chicken meats and beef liver contain lead [0,09μg.g - 1; 0,29μg.g - 1]. The limit value of 0,1μg.g - 1 is almost reached in beef and chicken meats, (ii) as far as cadmium is concerned, the five studied samples contain this analyte [0,02μg.g - 1; 0,9μg.g - 1]. Except the chicken liver of which the concentration (0,15μg.g - 1) exceeds the maximum permissible value (0,1μg.g - 1), the others are in conformity with the standards and appropriate to be consumed,(iii) iron is higher in the liver and kidney samples: beef liver 282mg.g - 1, chicken liver 250 mg.g - 1, pork kidney 247mg.g - 1. The study also showed that the calcium concentration in animal tissues is low and they can be classified as poor-calcium food. [fr

  9. Investigating the effects of ABC transporter-based acquired drug resistance mechanisms at the cellular and tissue scale.

    Science.gov (United States)

    Liu, Cong; Krishnan, J; Xu, Xiao Yun

    2013-03-01

    In this paper we systematically investigate the effects of acquired drug resistance at the cellular and tissue scale, with a specific focus on ATP-binding cassette (ABC) transporter-based mechanisms and contrast this with other representative intracellular resistance mechanisms. This is done by developing in silico models wherein the drug resistance mechanism is overlaid on a coarse-grained description of apoptosis; these cellular models are coupled with interstitial drug transport, allowing for a transparent examination of the effect of acquired drug resistances at the tissue level. While ABC transporter-mediated resistance mechanisms counteract drug effect at the cellular level, its tissue-level effect is more complicated, revealing unexpected trends in tissue response as drug stimuli are systematically varied. Qualitatively different behaviour is observed in other drug resistance mechanisms. Overall the paper (i) provides insight into the tissue level functioning of a particular resistance mechanism, (ii) shows that this is very different from other resistance mechanisms of an apparently similar type, and (iii) demonstrates a concrete instance of how the functioning of a negative feedback based cellular adaptive mechanism can have unexpected higher scale effects.

  10. First assessment of trace metal concentration in mangrove crab eggs and other tissues, SE Brazil.

    Science.gov (United States)

    de Almeida, Eduardo Vianna; Kütter, Vinicius Tavares; Marques, Eduardo Duarte; da Silva-Filho, Emmanoel Vieira

    2016-07-01

    The mangrove crab Ucides cordatus is widespread in the Brazilian coast, which has an important role in nutrient cycling. This species reproduces in summer and females carry eggs about a month, when they maintain contact with water and sediments. It remains unclear if trace metals can be absorbed or adsorbed by the eggs during development. The present study aims to investigate, for the first time, trace metal concentrations in ovigerous female tissues and eggs of U. cordatus in two areas with different metal pollution levels in the Southeastern Brazil. Samples were collected in two different mangroves, Guanabara Bay (GB) highly polluted environment and Paraíba do Sul River (PSR). In both populations, we observed significant increase of V, Cr, and Mn concentrations along eggs maturation. The higher metals averages were found in PSR population. This trend was reported since the 1990s and lower concentrations in GB marine organisms were attributed to reducing conditions, high organic load, and the presence of sulfide ions. These conditions restrict the bioavailability of metals in the bay, with exception of Mn. No significant differences were observed in gills and muscles. In both populations of the present study, V, Zn, As, and Pb were higher in eggs of initial stage, whereas Mn, Ni, Cu, and Cd were higher in hepatopancreas. Beside this, V, Cr, Mn, As, and Pb showed an increase concerning egg development. Thus, V, As, and Pb in eggs come from two sources previous discussed: females and environment. Zinc came mainly from females due to essential function. Those new information should be considered as one of the mechanisms of trace metal transfer to the trophic chain, between benthonic and pelagic environment.

  11. Secreted phospholipase A(2) as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Jørgensen, K.; Andresen, Thomas Lars

    2003-01-01

    Polymer-coated liposomes can act as versatile drug-delivery systems due to long vascular circulation time and passive targeting by leaky blood vessels in diseased tissue. We present an experimental model system illustrating a new principle for improved and programmable drug-delivery, which takes ...

  12. Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells and Tissues Following Combat Associated Trauma

    Science.gov (United States)

    2013-09-01

    death pathways such as apoptosis subsequent to acute trauma as soon as possible, ideally by self- administration of a drug or a biologic that can be... Drugs to Ocular Tissues Including Retina and Cornea . Mol Ther, 2007;16(1):107- 14. 3. Read SP, Cashman SM, and Kumar-Singh R: POD...1 AD_________________ Award Number: W81XWH-12-1-0374 TITLE: Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells

  13. Spatial distribution of theobromine--a low MW drug--in tissues via matrix-free NALDI-MS imaging.

    Science.gov (United States)

    Tata, Alessandra; Montemurro, Chiara; Porcari, Andreia M; Silva, Kamila C; Lopes de Faria, José B; Eberlin, Marcos N

    2014-09-01

    The ability of nano-assisted laser desorption-ionization mass spectrometry imaging (NALDI-IMS) to provide selective chemical monitoring with appropriate spatial distribution of a low molecular drug in a biological tissue was investigated. NALDI-IMS is a matrix-free laser desorption ionization (LDI) protocol based on imprinting of tissue constituents on a nanostructured surface. Using the accumulation of theobromine in rat kidney as a model, NALDI-IMS was found to provide well-resolved images of the special distribution of this low molecular weight (MW) drug in tissue. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

    Science.gov (United States)

    Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

    2013-06-01

    In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

  15. Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

    Science.gov (United States)

    Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

    2017-01-01

    Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

  16. Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung.

    Science.gov (United States)

    Rodvold, Keith A; Hope, William W; Boyd, Sara E

    2017-10-01

    Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e.g. area-under-the-curve) need to be incorporated with pharmacokinetic-pharmacodynamic indices so that rational dose selection can be identified for specific pathogens and types of pneumonic infection (community-acquired vs hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia). Although having measured plasma or lung concentration-time data from critically ill patients to incorporate into pharmacokinetic-pharmacodynamic models is very unlikely during drug development, it is essential that altered distribution, augmented renal clearance, and renal or hepatic dysfunction should be considered. Notably, the number of published studies involving microdialysis and intrapulmonary penetration of antibiotics has been limited and mainly involve beta-lactam agents, levofloxacin, and fosfomycin. Opportunities to measure in high-resolution effect site spatial pharmacokinetics (e.g. with MALDI-MSI or PET imaging) and in vivo continuous drug concentrations (e.g. with aptamer-based probes) now exist. Going forward these studies could be incorporated into antibiotic development programs for pneumonia in order to further increase the probability of candidate success. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Concentrations of trace elements in human tissues and relation of ratios of mutual metals to the human health

    International Nuclear Information System (INIS)

    Ling-wei, X.; Shao-xian, L.; Xiao-juan, Z.

    1989-01-01

    According to the experimental results, the concentrations and concentrations in order, of trace elements in human tissues among Changsha's People in China are reported. The authors particularly present that the ratios of mutual metals (M/N) in normal physiological tissues and fluids are very important factors which indicate the metabolic situations of trace elements in the body and as the indices which evaluate the situation of human health. (M and N mean the concentrations of different trace elements in the tissues or fluids, respectively.) Up to now, it is still an interesting field to study the functions of trace elements for the human health. There are previously some reports about the concentrations of trace elements in normal physiological tissues/ or organs and fluids of human body. These provide very valuable data for biological medicine. In the study presented atomic absorption method was adopted in order to determine the concentrations of Zn, Cu, Mn, Ni, Pb and Cd in human tissues (liver, spleen, kidney, bone, lung, pancreas, heart and artery and muscle) at autopsy. The authors suggest that trace elements, are contained in the body in an aproportional way, in normal physiological tissues and fluids, and the ratios may directly indicate metabolic situation of trace elements in the body which further reveal the mystery of trace elements for human health. Therefore, the ratios M/N as an indicator of health is more proper than that only using concentrations of trace elements. Schroeder (1973) reported that incidence of heart disease is related to the imbalance of ration Zn/Cd and Zn/Cu rather than the concentrations of Zn, Cd, Cu, and the intellectual development also depends on the proper proportion among copper, cadmium, lead, zinc in the body

  18. Effect of sucrose concentrations on Stevia rebaudiana Bertoni tissue culture and gene expression.

    Science.gov (United States)

    Ghorbani, T; Kahrizi, D; Saeidi, M; Arji, I

    2017-08-30

    Stevia rebaudiana (Bert.) Bertoni is known as sweet plant which it contains a high level of steviol glycosides in the leaves.  This plant has been used from centuries ago as a sweetener for tea. One of the most important steviol glycosides is stevioside that is attractive for diabetic persons. Tissue culture is the only rapid process for the mass propagation of stevia. One of the most important factors in the medium is sucrose that is a necessary for plant growth. In the present study, we use nodal segments of the stem as explants in mediums with different sucrose concentration (50 mM, 100mM and 150mM). Several morphological traits were measured in a 28 day period. Results analysis showed a significant variation between treatments. The highest growth rate, rooting and leaf production was obtained in medium with 100mM sucrose. The correlation between measured traits was significant at the 0.01 level. To investigation of UGT74G1, UGT76G1, UGT85C2 and KS genes expression that are involved in the synthesis of SGs, RT- PCR was done with the housekeeping gene of as internal control. There were significant differences between all media. The results showed thatsucrose 100 mM containing media was more desirable than others for expression of UGT76G1 and UGT85C2 genes. Whereas, the best medium for expression of UGT74G1 was sucrose 150 mM and sucrose 50 mM for KS gene. Totally, it seems that sucrose at a concentration of 100 mMprovides the best condition for stevia growth and steviol glycosides production.

  19. Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

    Science.gov (United States)

    Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

    2017-07-01

    The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

  20. Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

    DEFF Research Database (Denmark)

    Langberg, H; Bjørn, C; Boushel, Robert Christopher

    2002-01-01

    been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years...... increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P increases the interstitial concentrations......Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet...

  1. Dioxin concentration in milk, faeces and tissues of cows related to feed contamination

    Energy Technology Data Exchange (ETDEWEB)

    Schulz, A.J.; Kamphues, J. [Inst. of Animal Nutrition, School of Veterinary Medicine, Hannover (Germany); Wiesmueller, T. [Federal State Office for Consumer Protection, Potsdam (Germany); Appuhn, H. [Agricultural Investigation and Research Inst., Hameln (Germany); Stehr, D. [District Government of Lueneburg (Germany); Severin, K. [Chamber for Agriculture, Hannover (Germany); Landmann, D. [Agricultural Teaching and Research Facility, Echem (Germany)

    2004-09-15

    Dioxin contamination of feed and food is a frequently discussed problem, even in the press. The EU legislation sets maximum levels for dioxins in food and feeding stuffs. The dioxin concentration of milk, faeces and tissues of lactating cows grazing in an area of higher dioxin level in the soil and grass, has been tested in part 1 of this small scale field study. Soil intake of grazing cows can reach 1.5 kg soil/d under extreme meteorological conditions. Considering that, the dioxin load of soil and the degree of contamination of feedstuffs could play an important role regarding the exposition of grazing animals. Due to repeated flooding the area the experiment took place was known for a higher dioxin level in soil and grass. The area was separated in a depression and an elevation (in flooding areas depressions are known for their higher dioxin level). Grassland is not only used for grazing animals, but also to obtain hay or grass silage. In part 2 of the field study grass silage obtained on the same area, was fed to dry cows to test whether or not there a risk for milk quality after parturition. The primary aim of this field study was to investigate different matrices at different moments of the experiment. The secondary aim was to develop recommendations on how to prevent or at least how to minimize the dioxin load of feed and with it of food, if food producing animals graze on such areas.

  2. Research on the comparison of the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection.

    Science.gov (United States)

    Duan, Yi-Qin; Yang, Ye-Zhen; Huang, Xue-Tao; Lin, Ding

    2017-11-01

    To compare the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection. Sixty adult white rabbits were randomly assigned to the subtenon drug delivery group and the subconjunctival injection group. The subtenon drug delivery group was continuously infused demethylvancomycin to the subtenon of rabbits. The subconjunctival injection group was injected demethylvancomycin to the subconjunctival of rabbits. Cornea, iris and sclera were collected for high-performance liquid chromatography analyses to determine drug concentrations at one hour, three hours, six hours, 12 h and 24 h of drug administration. WinNonlin 6.3 was used to calculate the parameters of cumulative area under the curve (AUC cum ) of demethylvancomycin. The peak levels of demethylvancomycin concentration of the subtenon drug delivery group and the subconjunctival injection group were 92.406 ± 21.555 and 51.778 ± 14.001 μg/g in cornea, 28.451 ± 10.229 μg/g and 42.271 ± 27.291 μg/g in iris, 153.166 ± 51.738 μg/g and 57.423 ± 18.480 μg/g in sclera. The differences of concentrations between the two groups in cornea and sclera were statistically significant (F = 487.775, p drug delivery group and the subconjunctival injection group was 1808.23 h * μg/g and 273.73 h * μg/g in cornea, 489.12 h * μg/g and 216.16 h * μg/g in iris and 2166.34 h * μg/g and 392.57 h * μg/g in sclera at 24 h of drug administration. The sustained subtenon drug delivery had a better drug permeability and accumulation in the intraocular solid tissue compared to subconjunctival injection, which demonstrated it was probably a promising and effective approach for treating posterior segment diseases and endophthalmitis.

  3. Novel scalable silicone elastomer and poly(2-hydroxyethyl methacrylate) (PHEMA) composite materials for tissue engineering and drug delivery applications

    DEFF Research Database (Denmark)

    Mohanty, Soumyaranjan; Hemmingsen, Mette; Wojcik, Magdalena

    2013-01-01

    material with increased hydrophilicity in regard to virgin silicone elastomer, making it suitable as a scaffold for tissue engineering and with the concomitant possibility for delivering drug from the scaffold to the tissue. Interpenetrating polymer networks (IPNs) of silicone elastomer and PHEMA......In recent years hydrogels have received increasing attention as potential materials for applications in regenerative medicine. They can be used for scaffold materials providing structural integrity to tissue constructs, for controlled delivery of drugs and proteins to cell and tissues......, and for support materials in tissue growth. However, the real challenge is to obtain sufficiently good mechanical properties of the hydrogel. The present study shows the combination of two normally non-compatible materials, silicone elastomer and poly(2-hydroxyethyl methacrylate) (PHEMA), into a novel composite...

  4. Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin

    NARCIS (Netherlands)

    Broekmans, W.M.R.; Berendschot, T.T.J.R.; Klöpping-Ketelaars, I.A.A.; Vries, A.J. de; Goldbohm, R.A.; Tijburg, L.B.M.; Kardinaal, A.F.M.; Poppel, G. van

    2002-01-01

    Background: Macular pigment (MP), concentrated in the central area of the retina, contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk factor for age-related macular degeneration. Little information is available regarding MP density in relation to serum lutein and

  5. Adequate plasma drug concentrations suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps.

    Science.gov (United States)

    Arensdorff, Lyne; Boillat-Blanco, Noémie; Decosterd, Laurent; Buclin, Thierry; de Vallière, Serge

    2017-09-01

    Elastomeric pumps can be useful for the administration of antibiotics in the outpatient setting. To determine amoxicillin degradation in elastomeric pumps, as well as the effectiveness of amoxicillin treatment administered by elastomeric pumps. Antibiotic degradation was measured in elastomeric pumps filled with 6 g of amoxicillin in 240 mL of NaCl 0.9% by drawing samples at 12 h intervals when stored in the fridge for 48 h and when worn around the waist for 24 h. Subsequently nine patients were treated with continuous infusions of 8 or 12 g of amoxicillin per day. Plasma amoxicillin concentrations were measured on each visit to the outpatient parenteral antibiotic therapy unit. Clinical outcome was verified 3 months after the end of treatment. Amoxicillin degradation in elastomeric pumps reached 10% after 48 h in the fridge and an additional 30% when worn around the waist for 24 h. Mean plasma drug concentrations achieved with 12 g of amoxicillin per day were 18.5 mg/L (95% CI 13.5-23.5), which is largely above the MIC of amoxicillin-susceptible bacteria. Nine patients treated for various complicated infections were cured and had no unexpected adverse effects. Adequate plasma drug concentrations and favourable clinical outcomes suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps. This treatment modality does not fulfil formal requirements regarding pharmaceutical stability, but the resulting safety impact in patients is probably limited. Therapeutic drug monitoring and a close clinical follow-up are recommended if this route of administration is chosen. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

    Science.gov (United States)

    Lee, Kwang-Hun; Liapi, Eleni A; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A; Ventura, Veronica Prieto; Geschwind, Jean-Francois H

    2010-06-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  7. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    International Nuclear Information System (INIS)

    Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

    2010-01-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  8. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro.

    Directory of Open Access Journals (Sweden)

    Deborah G Nguyen

    Full Text Available Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI. This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM. Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level.

  9. Modeling and optimization of tissue 10B concentration and dosimetry for arbitrary BPA-F infusion schedules in humans

    International Nuclear Information System (INIS)

    Kiger, W.S. III; Newton, T.H.; Palmer, M.R.

    2000-01-01

    Separate compartmental models have been derived for the concentration of 10 B resulting from BPA-F infusion in the central vascular space (i.e., blood or, more appropriately, plasma) and in glioblastoma multiforme and normal brain. By coupling the model for the temporal variation of 10 B concentration in the central vascular space with that for tissue, the dynamic behavior of the 10 B concentration and the resulting dosimetry in the relevant tissues and blood may be predicted for arbitrary infusion schedules. This coupled model may be used as a tool for identifying the optimal time for BNCT irradiation and optimal BPA-F infusion schedule (i.e., temporal targeting) in humans without the need for expensive and time-consuming pharmacokinetic studies for every infusion schedule considered. This model was used to analyze the concentration profiles resulting from a wide range of infusion schedules and their implications for dosimetry. (author)

  10. Regenerative Medicine, Disease Modelling, and Drug Discovery in Human Pluripotent Stem Cell-Derived Kidney Tissue

    Directory of Open Access Journals (Sweden)

    Navin Gupta

    2017-08-01

    Full Text Available The multitude of research clarifying critical factors in embryonic organ development has been instrumental in human stem cell research. Mammalian organogenesis serves as the archetype for directed differentiation protocols, subdividing the process into a series of distinct intermediate stages that can be chemically induced and monitored for the expression of stage-specific markers. Significant advances over the past few years include established directed differentiation protocols of human embryonic stem cells and human induced pluripotent stem cells (hiPSC into human kidney organoids in vitro. Human kidney tissue in vitro simulates the in vivo response when subjected to nephrotoxins, providing a novel screening platform during drug discovery to facilitate identification of lead candidates, reduce developmental expenditures, and reduce future rates of drug-induced acute kidney injury. Patient-derived hiPSC, which bear naturally occurring DNA mutations, may allow for modelling of human genetic diseases to enable determination of pathological mechanisms and screening for novel therapeutics. In addition, recent advances in genome editing with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 enable the generation of specific mutations to study genetic disease, with non-mutated lines serving as an ideal isogenic control. The growing population of patients with end-stage kidney disease is a worldwide healthcare problem, with high morbidity and mortality rates, that warrants the discovery of novel forms of renal replacement therapy. Coupling the outlined advances in hiPSC research with innovative bioengineering techniques, such as decellularised kidney and three-dimensional printed scaffolds, may contribute to the development of bioengineered transplantable human kidney tissue as a means of renal replacement therapy.

  11. Concentrations of 17 elements, including mercury, in the tissues, food and abiotic environment of Arctic shorebirds

    International Nuclear Information System (INIS)

    Hargreaves, Anna L.; Whiteside, Douglas P.; Gilchrist, Grant

    2011-01-01

    Exposure to contaminants is one hypothesis proposed to explain the global decline in shorebirds, and is also an increasing concern in the Arctic. We assessed potential contaminants (As, Be, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Se, Tl, V, and Zn) at a shorebird breeding site in Nunavut, Canada. We compared element levels in soil, invertebrates and shorebird blood to assess evidence for bioconcentration and biomagnification within the Arctic-based food chain. We tested whether elements in blood, feathers and eggs of six shorebird species (Pluvialis squatarola, Calidris alpina, C. fuscicollis, Phalaropus fulicarius, Charadrius semipalmatus, and Arenaria interpres) were related to fitness endpoints: adult body condition, blood-parasite load, egg size, eggshell thickness, nest duration, and hatching success. To facilitate comparison to other sites, we summarise the published data on toxic metals in shorebird blood and egg contents. Element concentrations and invertebrate composition differed strongly among habitats, and habitat use and element concentrations differed among shorebird species. Hg, Se, Cd, Cu, and Zn bioconcentrated from soil to invertebrates, and Hg, Se and Fe biomagnified from invertebrates to shorebird blood. As, Ni, Pb, Co and Mn showed significant biodilution from soil to invertebrates to shorebirds. Soil element levels were within Canadian guidelines, and invertebrate Hg levels were below dietary levels suggested for the protection of wildlife. However, maximum Hg in blood and eggs approached levels associated with toxicological effects and Hg-pollution in other bird species. Parental blood-Hg was negatively related to egg volume, although the relationship varied among species. No other elements approached established toxicological thresholds. In conclusion, whereas we found little evidence that exposure to elements at this site is leading to the declines of the species studied, Hg, as found elsewhere in the Canadian Arctic, is of potential

  12. Concentrations of 17 elements, including mercury, in the tissues, food and abiotic environment of Arctic shorebirds

    Energy Technology Data Exchange (ETDEWEB)

    Hargreaves, Anna L., E-mail: alhargreaves@gmail.com [Calgary Zoo, Centre for Conservation Research, 1300 Zoo Rd NE, Calgary, AB, T2E 7V6 (Canada); Whiteside, Douglas P. [Calgary Zoo, Animal Health Centre, 1300 Zoo Rd NE, Calgary, AB, T2E 7V6 (Canada); University of Calgary, Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, 2500 University Dr. NW, Calgary, AB, T2N 1N4 (Canada); Gilchrist, Grant [Carleton University, National Wildlife Research Centre, Ottawa, ON, KIA OH3 (Canada)

    2011-09-01

    Exposure to contaminants is one hypothesis proposed to explain the global decline in shorebirds, and is also an increasing concern in the Arctic. We assessed potential contaminants (As, Be, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Se, Tl, V, and Zn) at a shorebird breeding site in Nunavut, Canada. We compared element levels in soil, invertebrates and shorebird blood to assess evidence for bioconcentration and biomagnification within the Arctic-based food chain. We tested whether elements in blood, feathers and eggs of six shorebird species (Pluvialis squatarola, Calidris alpina, C. fuscicollis, Phalaropus fulicarius, Charadrius semipalmatus, and Arenaria interpres) were related to fitness endpoints: adult body condition, blood-parasite load, egg size, eggshell thickness, nest duration, and hatching success. To facilitate comparison to other sites, we summarise the published data on toxic metals in shorebird blood and egg contents. Element concentrations and invertebrate composition differed strongly among habitats, and habitat use and element concentrations differed among shorebird species. Hg, Se, Cd, Cu, and Zn bioconcentrated from soil to invertebrates, and Hg, Se and Fe biomagnified from invertebrates to shorebird blood. As, Ni, Pb, Co and Mn showed significant biodilution from soil to invertebrates to shorebirds. Soil element levels were within Canadian guidelines, and invertebrate Hg levels were below dietary levels suggested for the protection of wildlife. However, maximum Hg in blood and eggs approached levels associated with toxicological effects and Hg-pollution in other bird species. Parental blood-Hg was negatively related to egg volume, although the relationship varied among species. No other elements approached established toxicological thresholds. In conclusion, whereas we found little evidence that exposure to elements at this site is leading to the declines of the species studied, Hg, as found elsewhere in the Canadian Arctic, is of potential

  13. Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations.

    Science.gov (United States)

    Ji, Yuan; Schaid, Daniel J; Desta, Zeruesenay; Kubo, Michiaki; Batzler, Anthony J; Snyder, Karen; Mushiroda, Taisei; Kamatani, Naoyuki; Ogburn, Evan; Hall-Flavin, Daniel; Flockhart, David; Nakamura, Yusuke; Mrazek, David A; Weinshilboum, Richard M

    2014-08-01

    Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT. Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects. Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10(-9) ) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10(-16) ), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation. In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors. © 2014 The British Pharmacological Society.

  14. Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

    Science.gov (United States)

    Chen, Muwan; Le, Dang QS; Hein, San; Li, Pengcheng; Nygaard, Jens V; Kassem, Moustapha; Kjems, Jørgen; Besenbacher, Flemming; Bünger, Cody

    2012-01-01

    Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT) cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug. PMID:22904634

  15. Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration

    Science.gov (United States)

    Laufer, Jan; Delpy, Dave; Elwell, Clare; Beard, Paul

    2007-01-01

    A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO2) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO2) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO2 and HHb, total haemoglobin concentration and SO2. The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of ±3.8 g l-1 (±58 µM) and ±4

  16. Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration

    Energy Technology Data Exchange (ETDEWEB)

    Laufer, Jan; Delpy, Dave; Elwell, Clare; Beard, Paul [Department of Medical Physics and Bioengineering, University College London, Malet Place Engineering Building, London WC1E 6BT (United Kingdom)

    2007-01-07

    A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO{sub 2}) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO{sub 2}) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO{sub 2} and HHb, total haemoglobin concentration and SO{sub 2}. The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of {+-}3

  17. Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration

    International Nuclear Information System (INIS)

    Laufer, Jan; Delpy, Dave; Elwell, Clare; Beard, Paul

    2007-01-01

    A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO 2 ) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO 2 ) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO 2 and HHb, total haemoglobin concentration and SO 2 . The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of ±3.8 g l -1 (±58

  18. Introduction for the special issue on recent advances in drug delivery across tissue barriers.

    Science.gov (United States)

    Mrsny, Randall J; Brayden, David J

    2016-01-01

    This special issue of Tissue Barriers contains a series of reviews with the common theme of how biological barriers established at epithelial tissues limit the uptake of macromolecular therapeutics. By improving our functional understanding of these barriers, the majority of the authors have highlighted potential strategies that might be applied to the non-invasive delivery of biopharmaceuticals that would otherwise require an injection format for administration. Half of the articles focus on the potential of particular technologies to assist oral delivery of peptides, proteins and other macromolecules. These include use of prodrug chemistry to improve molecule stability and permeability, and the related potential for oral delivery of poorly permeable agents by cell-penetrating peptides and dendrimers. Safety aspects of intestinal permeation enhancers are discussed, along with the more recent foray into drug-device combinations as represented by intestinal microneedles and externally-applied ultrasound. Other articles highlight the crossover between food research and oral delivery based on nanoparticle technology, while the final one provides a fascinating interpretation of the physiological problems associated with subcutaneous insulin delivery and how inefficient it is at targeting the liver.

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

    Science.gov (United States)

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

    2014-06-30

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

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

    Science.gov (United States)

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

    2014-01-01

    Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen. PMID:24975958

  1. Studies on the method for determination of fluoride concentration in rat hard tissues by neutron activation analysis using 20F

    International Nuclear Information System (INIS)

    Nakakura, Tadao

    1991-01-01

    Neutron activation analysis method (non disruptive analysis, short time period measurement) has been recognized as a high precision analysis of fluoride concentration in hard tissue. Heat neutron irradiation analysis using instrumental neutron activation analysis (INAA) method was used to investigate 20 F concentration. Results were as follows. F concentration in a dried material of hard tissue using INAA method can be fixed by measuring the 20 F's energy peak for 10 seconds after neutron irradiation under 1 x 10 n/cm 2 ·s for 10 seconds. Non responding time that is caused by short half reduction time of 20 F can be recovered enough by a revise calculation. Reproducibility of measured fluoride concentration using INAA method was well stabilized. Rat hard tissue which takes no fluoride can be determined fluoride concentration without sodium restriction. Femur fluoride concentrations using INAA method had significant correlation with conventional microdiffusion analysis method (r=0.997, regression line: Y=1.13X + 2.98). Increase of fluoride density in dentine of rat molars under growing period according to fluoride intake was 1/3 of femurs and mandibles. (author)

  2. Layer-by-layer assembled multilayers and polymeric nanoparticles for drug delivery in tissue engineering applications

    Science.gov (United States)

    Mehrotra, Sumit

    Tissues and organs in vivo are structured in three dimensional (3-D) ordered assemblies to maintain their metabolic functions. In the case of an injury, certain tissues lack the regenerative abilities without an external supportive environment. In order to regenerate the natural in vivo environment post-injury, there is a need to design three-dimensional (3-D) tissue engineered constructs of appropriate dimensions along with strategies that can deliver growth factors or drugs at a controlled rate from such constructs. This thesis focuses on the applications of hydrogen bonded (H-bonded) nanoscale layer-by-layer (LbL) assembled multilayers for time controlled drug delivery, fabrication of polymeric nanoparticles as drug delivery carriers, and engineering 3-D cellular constructs. Axonal regeneration in the central nervous system after spinal cord injury is often disorganized and random. To support linear axonal growth into spinal cord lesion sites, certain growth factors, such as brain-derived neurotrophic factor (BDNF), needs to be delivered at a controlled rate from an array of uniaxial channels patterned in a scaffold. In this study, we demonstrate for the first time that H-bonded LbL assembled degradable thin films prepared over agarose hydrogel, whereby the protein was loaded separately from the agarose fabrication, provided sustained release of protein under physiological conditions for more than four weeks. Further, patterned agarose scaffolds implanted at the site of a spinal cord injury forms a reactive cell layer of leptomeningeal fibroblasts in and around the scaffold. This limits the ability of axons to reinnervate the spinal cord. To address this challenge, we demonstrate the time controlled release of an anti-mitotic agent from agarose hydrdgel to control the growth of the reactive cell layer of fibroblasts. Challenges in tissue engineering can also be addressed using gene therapy approaches. Certain growth factors in the body are known to inhibit

  3. Investigation of the Relationship of Some Antihypertensive Drugs with Oxidant/Antioxidant Parameters and DNA Damage on Rat Uterus Tissue

    OpenAIRE

    Mustafa Talip Sener; Hamit Hakan Alp; Beyzagul Polat; Bunyamin Borekci; Yakup Kumtepe; Nesrin Gursan; Serkan Kumbasar; Suleyman Salman; Halis Suleyman

    2011-01-01

    Background In this study, we investigated the effects of treatment with chronic antihypertensive drugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine) on oxidant-antioxidant parameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examined histopathologically. Materials and Methods A total of 36 albino Wistar rats were divided into the following six groups: 0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg...

  4. A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

    Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

  5. Concentrations of cadmium and selected essential elements in malignant large intestine tissue

    Science.gov (United States)

    Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

    2015-01-01

    Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

  6. Tissue concentrations of prostate-specific antigen in prostatic carcinoma and benign prostatic hyperplasia.

    Science.gov (United States)

    Pretlow, T G; Pretlow, T P; Yang, B; Kaetzel, C S; Delmoro, C M; Kamis, S M; Bodner, D R; Kursh, E; Resnick, M I; Bradley, E L

    1991-11-11

    Prostate-specific antigen (PSA), as measured in peripheral blood, is currently the most widely used marker for the assessment of tumor burden in the longitudinal study of patients with carcinoma of the prostate (PCA). Studies from other laboratories have led to the conclusion that a given volume of PCA causes a much higher level of PSA in the peripheral circulation of patients than a similar volume of prostate without carcinoma. We have evaluated PSA in the resected tissues immunohistochemically and in extracts of PCA and of prostates resected because of benign prostatic hyperplasia (BPH) with an enzyme-linked immunosorbent assay. Immunohistochemical results were less quantitative than but consistent with the results of the ELISA of tissue extracts. Immunohistochemically, there was considerable heterogeneity in the expression of PSA by both PCA and BPH both within and among prostatic tissues from different patients. While the levels of expression of PSA in these tissues overlap broadly, PSA is expressed at a lower level in PCA than in BPH when PSA is expressed as a function of wet weight of tissue (p = 0.0095), wet weight of tissue/% epithelium (p less than 0.0001), protein extracted from the tissue (p = 0.0039), or protein extracted/% epithelium (p less than 0.0001).

  7. Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

    Directory of Open Access Journals (Sweden)

    Chen M

    2012-08-01

    Full Text Available Muwan Chen,1,2 Dang QS Le,1,2 San Hein,2 Pengcheng Li,1 Jens V Nygaard,2 Moustapha Kassem,3 Jørgen Kjems,2 Flemming Besenbacher,2 Cody Bünger11Orthopaedic Research Lab, Aarhus University Hospital, Aarhus C, Denmark; 2Interdisciplinary Nanoscience Center (iNANO, Aarhus University, Aarhus C, Denmark; 3Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, DenmarkAbstract: Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other

  8. Tissue radionuclide concentrations in water birds and upland birds on the Hanford Site (USA) from 1971-2009

    International Nuclear Information System (INIS)

    Delistraty, Damon; Van Verst, Scott

    2011-01-01

    Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result, there is a need to characterize contaminant effects on site biota. Within this framework, the main purpose of our study was to evaluate radionuclide concentrations in bird tissue, obtained from the Hanford Environmental Information System (HEIS). The database was sorted by avian group (water bird vs. upland bird), radionuclide (over 20 analytes), tissue (muscle, bone, liver), location (onsite vs. offsite), and time period (1971-1990 vs. 1991-2009). Onsite median concentrations in water birds were significantly higher (Bonferroni P < 0.05) than those in onsite upland birds for Cs-137 in muscle (1971-1990) and Sr-90 in bone (1991-2009), perhaps due to behavioral, habitat, or trophic species differences. Onsite median concentrations in water birds were higher (borderline significance with Bonferroni P = 0.05) than those in offsite birds for Cs-137 in muscle (1971-1990). Onsite median concentrations in the earlier time period were significantly higher (Bonferroni P < 0.05) than those in the later time period for Co-60, Cs-137, Eu-152, and Sr-90 in water bird muscle and for Cs-137 in upland bird muscle tissue. Median concentrations of Sr-90 in bone were significantly higher (Bonferroni P < 0.05) than those in muscle for both avian groups and both locations. Over the time period, 1971-2009, onsite median internal dose was estimated for each radionuclide in water bird and upland bird tissues. However, a meaningful dose comparison between bird groups was not possible, due to a dissimilar radionuclide inventory, mismatch of time periods for input radionuclides, and lack of an external dose estimate. Despite these limitations, our results contribute toward ongoing efforts to characterize ecological risk at the Hanford Site. - Highlights: → Radionuclides evaluated in bird tissues on the Hanford Site

  9. Tissue radionuclide concentrations in water birds and upland birds on the Hanford Site (USA) from 1971-2009

    Energy Technology Data Exchange (ETDEWEB)

    Delistraty, Damon, E-mail: DDEL461@ecy.wa.gov [Washington State Department of Ecology, N. 4601 Monroe Street, Spokane, WA 99205-1295 (United States); Van Verst, Scott [Washington State Department of Health, Olympia, WA (United States)

    2011-08-15

    Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result, there is a need to characterize contaminant effects on site biota. Within this framework, the main purpose of our study was to evaluate radionuclide concentrations in bird tissue, obtained from the Hanford Environmental Information System (HEIS). The database was sorted by avian group (water bird vs. upland bird), radionuclide (over 20 analytes), tissue (muscle, bone, liver), location (onsite vs. offsite), and time period (1971-1990 vs. 1991-2009). Onsite median concentrations in water birds were significantly higher (Bonferroni P < 0.05) than those in onsite upland birds for Cs-137 in muscle (1971-1990) and Sr-90 in bone (1991-2009), perhaps due to behavioral, habitat, or trophic species differences. Onsite median concentrations in water birds were higher (borderline significance with Bonferroni P = 0.05) than those in offsite birds for Cs-137 in muscle (1971-1990). Onsite median concentrations in the earlier time period were significantly higher (Bonferroni P < 0.05) than those in the later time period for Co-60, Cs-137, Eu-152, and Sr-90 in water bird muscle and for Cs-137 in upland bird muscle tissue. Median concentrations of Sr-90 in bone were significantly higher (Bonferroni P < 0.05) than those in muscle for both avian groups and both locations. Over the time period, 1971-2009, onsite median internal dose was estimated for each radionuclide in water bird and upland bird tissues. However, a meaningful dose comparison between bird groups was not possible, due to a dissimilar radionuclide inventory, mismatch of time periods for input radionuclides, and lack of an external dose estimate. Despite these limitations, our results contribute toward ongoing efforts to characterize ecological risk at the Hanford Site. - Highlights: > Radionuclides evaluated in bird tissues on the Hanford Site

  10. 226Ra concentrations in crayfish tissues, water, and sediments from the Serpent River Basin in Northeastern Ontario, Canada

    International Nuclear Information System (INIS)

    Alikhan, M.A.

    1996-01-01

    Lower Serpent River, as well as Elliot, McCarthy and McCabe lakes had highest 226 Ra contamination, Chrisman, Quirke and Whiskey lakes a moderate one, Flack and Semiwhite lakes and the 'distant' control, Lake Wanapitei, the lowest. 226 Ra activity in Cambarus robustus tissues was directly related to their background levels. Thus, concentration coefficient (tissue/sediment concentrations) for 226 Ra ranged from 0.53 to 0.74 in highly contaminated Elliot and McCarthy lakes, 0.28 to 0.59 in moderately contaminated Quirke and Whiskey lakes, and from 0.27 to 3.44 in least contaminated Semiwhite and Flack lakes. Among various organs analysed, exoskeleton showed the highest (43.04 - 90.69%) and the tail muscles the lowest (2.95 -17.14%) 226 Ra activity. 226 Ra concentrations in the alimentary canal were considered a part of the ambient environment as they had not been absorbed

  11. Determination of Pu-239, 240 tissue concentrations in non-occupationally exposed residents of New York City

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Cohen, N.

    1977-01-01

    The study reports on the Pu-239, 240 concentrations in various tissues obtained from individuals residing in New York City. Twenty-six tissue samples have been analyzed for their Pu-239, 240 content, which include sections from the right lung, the liver, bone (4th and 5th vertebrae) and the kidney. The tissues were obtained at autopsy from a selected population not occupationally exposed to plutonium and whose deaths were the result of causes other than metabolic disorders. A detailed description is presented of the radiochemical procedures employed to separate Pu and electrochemically deposit plutonium isotopes prior to alpha spectrometry with Si surface-barrier detectors. Results of these measurements are given as activity per gram wet weight and activity per gram of calcium in the individual tissue. All results have been compared to similar measurements made at other laboratories and with estimates of concentration based on metabolic models. To date, the magnitudes and the distribution of the measured values are consistent with the values inferred from the ICRP lung model and measured concentrations of air

  12. Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism.

    Science.gov (United States)

    Alfadda, Assim A; Sallam, Reem M; Chishti, Muhammad Azhar; Moustafa, Amr S; Fatma, Sumbul; Alomaim, Waleed S; Al-Naami, Mohammed Y; Bassas, Abdulelah F; Chrousos, George P; Jo, Hyunsun

    2012-06-01

    Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.

  13. Inter-species variations in metal concentration in the soft tissue of some molluscs from the coasts of Aden Governorate

    International Nuclear Information System (INIS)

    Ali, A. A.; Baharoon, A. Ab.

    2002-01-01

    Nearly most of the molluscs are considered as good biomonitors for heavy metals pollution due to their mode of life, but there are differences in the bioavailability of heavy metals in their soft tissues. This research shows that Turbo coronatus and A canthopleura haddoni are the best to accumulate Cd, Pb, Co, Cr, As for Ni, P. perna and the latter two speciments show higher concentrations. Turbo coronatus and Ostrea cucullata are the best to accumulate Cu, and Zn. A canthopleura haddoni and Veneridae pitar sp. show higher availability of Fe, and Mn in their soft tissues. (author)

  14. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  15. Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan Amazon Parrots (Amazona ventralis).

    Science.gov (United States)

    Beaufrère, Hugues; Papich, Mark G; Brandão, João; Nevarez, Javier; Tully, Thomas N

    2015-03-01

    Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon parrots. While hypercholesterolemia and dyslipidemia have not definitely been associated with increased susceptibility to atherosclerosis in parrots, these are important and well-known risk factors in humans. Therefore statin drugs such as rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the prevention of atherosclerosis. No pharmacologic studies have been performed in psittacine birds despite the high prevalence of atherosclerosis in captivity. Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10 mg/kg of rosuvastatin with blood sampling performed according to a balanced incomplete block design over 36 hours. Because low plasma concentrations were produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in 2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of quantitation. For the 10 mg/kg study, the median peak plasma concentration and time to peak plasma concentration were 0.032 μg/mL and 2 hours, respectively. Our results indicate that rosuvastatin does not appear suitable in Amazon parrots as compounded and used at the dose in this study. Pharmacodynamic studies investigating lipid-lowering effects of statins rather than pharmacokinetic studies may be more practical and cost effective in future studies to screen for a statin with more ideal properties for potential use in psittacine dyslipidemia and atherosclerotic diseases.

  16. Select tissue mineral concentrations and chronic wasting disease status in mule deer from North-central Colorado.

    Science.gov (United States)

    Wolfe, Lisa L; Conner, Mary M; Bedwell, Cathy L; Lukacs, Paul M; Miller, Michael W

    2010-07-01

    Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (> or = 2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populations in north-central Colorado, United States, where CWD occurs naturally; we also measured copper concentrations in brain-stem (medulla oblongata at the obex) tissue from 181 of these deer. Analyses revealed a wide range of concentrations of all three minerals among sampled deer (copper: 5.6-331 ppm in liver, 1.5-31.9 ppm in obex; manganese: 0.1-21.4 ppm in liver; molybdenum: 0.5-4.0 ppm in liver). Bayesian multiple regression analysis revealed a negative association between obex copper (-0.097; 95% credible interval -0.192 to -0.006) and the probability of sampled deer also being infected with CWD, as well as a positive association between liver manganese (0.158; 95% credible interval 0.066 to 0.253) and probability of infection. We could not discern whether the tendencies toward lower brain-stem copper concentrations or higher systemic manganese concentrations in infected deer preceded prion infection or rather were the result of infection and its subsequent effects, although the distribution of trace mineral concentrations in infected deer seemed more suggestive of the latter.

  17. The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

    Directory of Open Access Journals (Sweden)

    C. Biz

    2009-12-01

    Full Text Available Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1 overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4 and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old were treated for three weeks with T4 (50 µg/day, Hyper or with saline (control. Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM or T3 (100 nM. PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA. Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

  18. High-spatial-resolution mapping of the oxygen concentration in cortical tissue (Conference Presentation)

    Science.gov (United States)

    Jaswal, Rajeshwer S.; Yaseen, Mohammad A.; Fu, Buyin; Boas, David A.; Sakadžic, Sava

    2016-03-01

    Due to a lack of imaging tools for high-resolution imaging of cortical tissue oxygenation, the detailed maps of the oxygen partial pressure (PO2) around arterioles, venules, and capillaries remain largely unknown. Therefore, we have limited knowledge about the mechanisms that secure sufficient oxygen delivery in microvascular domains during brain activation, and provide some metabolic reserve capacity in diseases that affect either microvascular networks or the regulation of cerebral blood flow (CBF). To address this challenge, we applied a Two-Photon PO2 Microscopy to map PO2 at different depths in mice cortices. Measurements were performed through the cranial window in the anesthetized healthy mice as well as in the mouse models of microvascular dysfunctions. In addition, microvascular morphology was recorded by the two-photon microscopy at the end of each experiment and subsequently segmented. Co-registration of the PO2 measurements and exact microvascular morphology enabled quantification of the tissue PO2 dependence on distance from the arterioles, capillaries, and venules at various depths. Our measurements reveal significant spatial heterogeneity of the cortical tissue PO2 distribution that is dominated by the high oxygenation in periarteriolar spaces. In cases of impaired oxygen delivery due to microvascular dysfunction, significant reduction in tissue oxygenation away from the arterioles was observed. These tissue domains may be the initial sites of cortical injury that can further exacerbate the progression of the disease.

  19. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  20. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from......Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  1. X-ray fluorescence analysis (XRF) and secondary ion mass spectrometry (SIMS) for analysis of iodine concentration in vitro in benign and malignant thyroid tissue

    International Nuclear Information System (INIS)

    Hansson, Marie; Berg, Gertrud; Ericsson, Lars; Grunditz, Torsten; Isaksson, Mats; Jansson, Svante; Nystrom, Ernst; Sodervall, Ulf

    2005-01-01

    Full text: The thyroid ability to store and concentrate iodine is of importance for radioiodine therapy in thyroid cancer. It is known that a normal thyroid contains 2-20 mg iodine while the information regarding malignant thyroid tissue is scarce. The purpose of this study was to investigate the iodine concentration in benign compared to malignant tissue. Methods: Thyroid tissue samples from healthy patients and from patients with papillary cancer were collected and frozen in connection with surgery. For the thyroid cancer patients, tissue was taken from both benign and malignant tissue. The iodine concentration was analysed with an XRF system consisting of a 241-Am source and an HPGe detector. When irradiating iodine containing tissue, characteristic X-rays are emitted. That radiation is detected with the strength of the detected signal being proportional to the amount of iodine in the sample. SIMS was used on glutaraldehyde fixed tissue as a histological tool for quantification and localization of iodine by sputtering and analysis of secondary ions. Results: The iodine concentration in benign tissue is considerably higher than in malignant samples. XRF measurements showed a medium iodine concentration in healthy thyroid tissue of 0.5 mg/mL. For the cancer patients, the iodine concentration was 0.3 mg/mL in benign tissue while no iodine could be detected in the malignant samples. These findings were consistent with the results from the SIMS investigation that gave a 100 times lower iodine concentration in malignant than in benign tissue. SIMS also showed that the iodine in benign tissue was predominantly located in the follicle lumen, while in the cancer cells low iodine concentration was found intra cellular as well as in the lumen. Conclusion: Iodine concentration in tissue from papillary cancer can be 100 times lower than in normal thyroid tissue. This is in accordance with the empirical knowledge that thyroid cancer should need about 100 times higher activity

  2. Allometric relationships to liver tissue concentrations of cyclic volatile methyl siloxanes in Atlantic cod

    International Nuclear Information System (INIS)

    Warner, Nicholas A.; Nøst, Therese H.; Andrade, Hector; Christensen, Guttorm

    2014-01-01

    Spatial distribution and relationship of allometric measurements (length, weight and age) to liver concentrations of cyclic volatile methyl siloxanes (cVMS) including octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclosiloxane (D6) in Atlantic cod (Gadus morhua) collected near the community of Tromsø in Northern Norway were assessed. These congeners were benchmarked against known persistent polychlorinated biphenyls (PCBs 153 and 180) to assess accumulation behavior of cVMS. D5 was the dominate cVMS detected in all fish livers with lipid normalized concentrations up to 10 times or greater than those observed for PCB 153 and 180. D4 and D6 concentration were negatively correlated with fish length and weight, indicating a greater elimination capacity compared to uptake processes with increasing fish size for these chemicals. These results indicate relationships between allometric measurements and cVMS concentrations may account for concentration variations observed within fish and should be assessed in future studies evaluating cVMS bioaccumulation potential. - Highlights: • cVMS spatial distribution investigated within cod surrounding an Arctic community. • Highest cVMS concentrations detected in biota collected near human settlements. • Cod liver concentrations of D5 were higher compared to PCBs. • D4 and D6 liver concentrations were negatively correlated with fish length/weight. - Liver concentrations of cVMS congeners decreased with increasing fish length and weight in Atlantic cod collected near emission sources of cVMS

  3. Trace metal concentrations in edible muscle tissues of some locally marketed fish

    International Nuclear Information System (INIS)

    Ansari, T.M.; Ichokitar, M.Y.; Ashraf, M.

    2000-01-01

    Edible muscle tissues of five fish species marketed in Multan, i.e., Rohu (Labeo rohita). (Labeo calhasu). Mori (cirrina inrigala). Ichagga (Rita rita) and Singliaree (mystus (osteobagrus) nor) have been analyzed quantitatively for trace elements, essential as well as toxic, using flame atomic absorption spectrometry. Dry ashing procedure has been employed to prepare sample solutions. Result indicate that edible muscle tissue of these fish, in general, contain higher amounts of potassium, calcium, sodium and magnesium, moderate quantities of zinc and iron and lessor amounts of copper and manganese. However, cadmium and lead were found to be below the limit of detection. (author)

  4. Herbicide-induced experimental variegate porphyria in mice: tissue porphyrinogen accumulation and response to porphyrogenic drugs.

    Science.gov (United States)

    Krijt, J; Stranska, P; Maruna, P; Vokurka, M; Sanitrak, J

    1997-01-01

    Administration of oxadiazon or oxyfluorfen (1000 ppm in the diet) to male BALB/c mice for 9 days resulted in experimental porphyria, resembling the acute phase of human variegate porphyria. Urinary concentrations of 5-aminolevulinic acid and porphobilinogen reached 1500 and 3000 mumol/L, respectively. Both herbicides caused a decrease of protoporphyrinogen oxidase activity in liver and kidney. Brain protoporphyrinogen oxidase activity was not altered. Liver and kidney porphyrin content increased to 11 and 17 nmol/g, respectively (control mice, 2 nmol/g). Over 50% of liver and kidney porphyrins were in the reduced (porphyrinogen) form. Bile of oxadiazon-treated mice contained 700 nmol/mL of protoporphyrinogen (control mice, 15 nmol/mL). Porphyrin content of the trigeminal nerve increased from 1 nmol/g in control animals to 11 nmol/g in oxadiazon-treated animals, suggesting a possible contribution of peripheral nerve porphyrins to porphyric neuropathy. Mice treated with 125 ppm of oxadiazon in the diet for 9 days excreted moderately elevated levels of porphobilinogen in urine (control mice, less than 50 mumol/L; treated mice, 330 mumol/L). Administration of phenobarbital or phenytoin (single injections on days 7, 8, and 9) increased the urinary porphobilinogen concentration to 3500 mumol/L. This response to porphyrogenic drugs resembles the response observed in human acute porphyrias.

  5. Are predictions of cancer response to targeted drugs, based on effects in unrelated tissues, the 'Black Swan' events?

    Science.gov (United States)

    Kurbel, Beatrica; Golem, Ante Zvonimir; Kurbel, Sven

    2015-01-01

    Adverse effects of targeted drugs on normal tissues can predict the cancer response. Rash correlates with efficacy of erlotinib, cetuximab and gefitinib and onset of arterial hypertension with response to bevacizumab, sunitinib, axitinib and sorafenib, possible examples of 'Black Swan' events, unexpected scientific observations, as described by Karl Popper in 1935. The proposition is that our patients have individual intrinsic variants of cell growth control, important for tumor response and adverse effects on tumor-unrelated tissue. This means that the lack of predictive side effects in healthy tissue is linked with poor results of tumor therapy when tumor resistance is caused by mechanisms that protect all cells of that patient from the targeted drug effects.

  6. 3D Printing of Calcium Phosphate Ceramics for Bone Tissue Engineering and Drug Delivery.

    Science.gov (United States)

    Trombetta, Ryan; Inzana, Jason A; Schwarz, Edward M; Kates, Stephen L; Awad, Hani A

    2017-01-01

    Additive manufacturing, also known as 3D printing, has emerged over the past 3 decades as a disruptive technology for rapid prototyping and manufacturing. Vat polymerization, powder bed fusion, material extrusion, and binder jetting are distinct technologies of additive manufacturing, which have been used in a wide variety of fields, including biomedical research and tissue engineering. The ability to print biocompatible, patient-specific geometries with controlled macro- and micro-pores, and to incorporate cells, drugs and proteins has made 3D-printing ideal for orthopaedic applications, such as bone grafting. Herein, we performed a systematic review examining the fabrication of calcium phosphate (CaP) ceramics by 3D printing, their biocompatibility in vitro, and their bone regenerative potential in vivo, as well as their use in localized delivery of bioactive molecules or cells. Understanding the advantages and limitations of the different 3D printing approaches, CaP materials, and bioactive additives through critical evaluation of in vitro and in vivo evidence of efficacy is essential for developing new classes of bone graft substitutes that can perform as well as autografts and allografts or even surpass the performance of these clinical standards.

  7. Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening.

    Science.gov (United States)

    Smith, Alec S T; Macadangdang, Jesse; Leung, Winnie; Laflamme, Michael A; Kim, Deok-Ho

    Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. Published by Elsevier Inc.

  8. 3D Printing of Calcium Phosphate Ceramics for Bone Tissue Engineering and Drug Delivery

    Science.gov (United States)

    Trombetta, Ryan; Inzana, Jason A.; Schwarz, Edward M.; Kates, Stephen L.; Awad, Hani A.

    2016-01-01

    Additive manufacturing, also known as 3D printing, has emerged over the past 3 decades as a disruptive technology for rapid prototyping and manufacturing. Vat polymerization, powder bed fusion, material extrusion, and binder jetting are distinct technologies of additive manufacturing, which have been used in a wide variety of fields, including biomedical research and tissue engineering. The ability to print biocompatible, patient-specific geometries with controlled macro- and micropores, and to incorporate cells, drugs and proteins has made 3D-printing ideal for orthopaedic applications, such as bone grafting. Herein, we performed a systematic review examining the fabrication of calcium phosphate (CaP) ceramics by 3D printing, their biocompatibility in vitro, and their bone regenerative potential in vivo, as well as their use in localized delivery of bioactive molecules or cells. Understanding the advantages and limitations of the different 3D printing approaches, CaP materials, and bioactive additives through critical evaluation of in vitro and in vivo evidence of efficacy is essential for developing new classes of bone graft substitutes that can perform as well as autografts and allografts or even surpass the performance of these clinical standards. PMID:27324800

  9. The Impact of Serum Drug Concentration on the Efficacy of Imipramine, Pregabalin and their Combination in Painful Polyneuropathy

    DEFF Research Database (Denmark)

    Sindrup, Søren Hein; Holbech, Jakob Vormstrup; Bach, Flemming W

    2017-01-01

    OBJECTIVE: The serum concentration-effect relation was explored for first line drugs in neuropathic pain and aimed to determine if efficacy could be increased. METHODS: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin and their combination in painful...... polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0-10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography. RESULTS: In 47 patients pain was reduced -1.0 (95% CI -1.5:-0.6) by imipramine, -0.......178). There was no correlation between drug concentration and pain reduction for imipramine (r= 0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine

  10. Food habits and radionuclide tissue concentrations of Nevada desert bighorn sheep, 1972--1973

    International Nuclear Information System (INIS)

    Brown, K.W.; Smith, D.D.; Bernhardt, D.E.; Giles, K.R.; Helvie, J.B.

    1976-06-01

    The botanical composition of the diet and radionuclide content of selected tissues of desert bighorn sheep (Ovis canadensis nelsoni) collected during the 1972 and 1973 hunting seasons were determined by analyzing rumen contents, and lung, liver, kidney, and bone tissues. Botanical examination of the rumen contents showed that grass exceeded 50 percent of the diet of 10 to 14 animals collected in 1972 and 12 of 18 animals collected in 1973. Desert needlegrass (Stipa speciosa), Indian rice grass (Oryzopsis hymenoides), and squirrel tail (Sitanion hystrix) were the major grasses utilized. The dominant shrub species consumed included the joint firs (Ephedra viridis) and (Ephedra nevadensis), Mohave yucca (Yucca schidigera), and cliff rose (Cowania mexicana). With the exception of potassium-40, gamma-emitting radionuclides were not detected in desert bighorn sheep tissue. The tritium levels reported were within environmental levels. Strontium-90 levels averaged 4.9 and 4.1 pCi/gram of bone ash for 1972 and 1973, respectively, continuing the downward trend observed in recent years. Uranium levels were similar to those reported from cattle grazing the same general geographic areas. The daily consumption for one year of 500 grams of liver containing the highest levels of plutonium and uranium would result in a dose to the human bone, the tissue expected to receive the highest dose, of approximately 1 mrem/year. This is less than 1% of the radiation protection guides for the general population

  11. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We rep...

  12. Concentrations of transuranic elements in critical organs and tissues of goats (CAPRA HIRCUS)

    International Nuclear Information System (INIS)

    Averin, V.S.; Vaskovtsova, V.A.; Kuhtsevich, A.B.; Tagai, S.A.; Tsarenok, A.A.; Buzdalkin, K.N.; Gvozdik, A.F.; Makarovets, I.V.; Nilova, E.K.

    2012-01-01

    Parameters of Am 241 and Pu 238, 239+240 transfer from the dietary soil-based component (mineral soil) to organs and tissues of goats during a grazing period of 80 and 160 days have been determined. The maximum specific activities of transuranic elements have been found in liver of goats. (authors)

  13. Whole-body γ-irradiation effects on catecholamine concentration in animal tissues

    International Nuclear Information System (INIS)

    Makashev, Zh.K.; Uteshev, T.A.; Abylaev, Zh. A.; Zhurnist, A.G.

    2003-01-01

    On the whole-body gamma-radiation activity in the exchanges of catecholamines (adrenalin and non-adrenalin) and their predecessors (dopamine and DOPA) in the rats tissue organism, indicate the infringement of irradiated animals in different links of biological synthesis the bio-gen amines in different phases of the radiation: DOPA→dopamine, dopamine→adrenalin, adrenalin→non-adrenalin. (author)

  14. Multiscale Modeling of Antibody Drug Conjugates: Connecting tissue and cellular distribution to whole animal pharmacokinetics and potential implications for efficacy

    Science.gov (United States)

    Cilliers, Cornelius; Guo, Hans; Liao, Jianshan; Christodolu, Nikolas; Thurber, Greg M.

    2016-01-01

    Antibody drug conjugates exhibit complex pharmacokinetics due to their combination of macromolecular and small molecule properties. These issues range from systemic concerns, such as deconjugation of the small molecule drug during the long antibody circulation time or rapid clearance from non-specific interactions, to local tumor tissue heterogeneity, cell bystander effects, and endosomal escape. Mathematical models can be used to study the impact of these processes on overall distribution in an efficient manner, and several types of models have been used to analyze varying aspects of antibody distribution including physiologically based pharmacokinetic (PBPK) models and tissue-level simulations. However, these processes are quantitative in nature and cannot be handled qualitatively in isolation. For example, free antibody from deconjugation of the small molecule will impact the distribution of conjugated antibodies within the tumor. To incorporate these effects into a unified framework, we have coupled the systemic and organ-level distribution of a PBPK model with the tissue-level detail of a distributed parameter tumor model. We used this mathematical model to analyze new experimental results on the distribution of the clinical antibody drug conjugate Kadcyla in HER2 positive mouse xenografts. This model is able to capture the impact of the drug antibody ratio (DAR) on tumor penetration, the net result of drug deconjugation, and the effect of using unconjugated antibody to drive ADC penetration deeper into the tumor tissue. This modeling approach will provide quantitative and mechanistic support to experimental studies trying to parse the impact of multiple mechanisms of action for these complex drugs. PMID:27287046

  15. Assessment of 90Sr and 137Cs activity concentration in human tissues in Hungary following the Chernobyl accident

    International Nuclear Information System (INIS)

    Turai, I.; Sztanyik, B.L.

    1997-01-01

    Artificial radioisotope contamination of tissue samples of Hungarian citizens has been regularly monitored by our Institute since 1978. 90 Sr concentration of both extracted deciduous teeth and rib samples showed a slight but permanent tendency to decrease since then. 137 Cs content in the body of Hungarian individuals was monitored by whole body counter from the mid of 60s for about a decade while it became lower of the minimum detection limit (MDL). It could again be detected by in vivo measurements in May 1986, however, the 137 Cs content of human beings in Hungary fell below the detection limit within two years. Thus, the monitoring could only be continued by in vitro measuring of the 137 Cs activity concentration in human soft tissue samples

  16. Tissue vitamin concentrations are maintained constant by changing the urinary excretion rate of vitamins in rats' restricted food intake.

    Science.gov (United States)

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2014-01-01

    We previously reported that mild food restriction induces a reduction in tryptophan-nicotinamide conversion, which helps to explain why death secondary to pellagra is pandemic during the hungry season. In this study, we investigated the levels of B-group vitamins in the liver, kidney, blood, and urine in rats that underwent gradual restriction of food intake (80, 60, 40, and 20% restriction vs. ad libitum food intake). No significant differences in the B-group vitamin concentrations (mol/g tissue) in the liver and kidney were observed at any level of food restriction. However, the urine excretion rates exhibited some characteristic phenomena that differed by vitamin. These results show that the tissue concentrations of B-group vitamins were kept constant by changing the urinary elimination rates of vitamins under various levels of food restriction. Only vitamin B12 was the only (exception).

  17. Effect of Graphite Concentration on Shear-Wave Speed in Gelatin-Based Tissue-Mimicking Phantoms

    Science.gov (United States)

    Anderson, Pamela G.; Rouze, Ned C.; Palmeri, Mark L.

    2011-01-01

    Elasticity-based imaging modalities are becoming popular diagnostic tools in clinical practice. Gelatin-based, tissue mimicking phantoms that contain graphite as the acoustic scattering material are commonly used in testing and validating elasticity-imaging methods to quantify tissue stiffness. The gelatin bloom strength and concentration are used to control phantom stiffness. While it is known that graphite concentration can be modulated to control acoustic attenuation, the impact of graphite concentrationon phantom elasticity has not been characterized in these gelatin phantoms. This work investigates the impact of graphite concentration on phantom shear stiffness as characterized by shear-wave speed measurements using impulsive acoustic-radiation-force excitations. Phantom shear-wave speed increased by 0.83 (m/s)/(dB/(cm MHz)) when increasing the attenuation coefficient slope of the phantom material through increasing graphite concentration. Therefore, gelatin-phantom stiffness can be affected by the conventional ways that attenuation is modulated through graphite concentration in these phantoms. PMID:21710828

  18. Tissue concentration-time profile of selenium after sodium selenite administration to rats

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Megumi; Natsuhori, Masahiro; Ito, Nobuhiko [Department of Veterinary Radiology and Radiation Biology, Kitasato University School of Veterinary Medicine, Towada, Aomori (Japan); Sera, Koichiro [Cyclotron Research Center, Iwate Medical University, Takizuka, Iwate (Japan); Futatsugawa, Shoji [Nishina Memorial Cyclotron Center (NMCC), Takizuka, Iwate (Japan)

    1999-07-01

    Selenium (Se) concentration-time profiles in plasma and organs including liver, kidney, heart, lung, spleen and brain of rats (Jcl Wister, 9 wks old, n=32) were investigated after a single intravenous (iv) / oral (po) administration of sodium selenite (dose is equivalent to 2 mg/kg b.w. of Se). The Se concentration was determined by PIXE analysis. Among the investigated biological samples, Se concentration was the highest in the kidney or liver, followed by the heart, lung or spleen, then plasma, and the brain. Se concentrations in these organs were 0.5 to 5 times of plasma Se. The distribution profiles of Se in the organs were dependent on the route of administration. Furthermore, their profiles appeared almost parallel to the plasma Se-concentration in a logarithmic scale. Compared to the Se concentration-time profiles in plasma and organs by the route of administration, po group showed about 1/4-1/2 of the Se concentration in iv group except for kidney. Kidney kept relatively higher concentration of Se, which was similar in the both groups. This may explain our recently published data that urinary excretion was similar in the both groups. The relative oral bioavailability of plasma and each organ was calculated by the ratio of area under the concentration-time curve after oral administration (AUCpo) to AUCiv. Each organ appeared to have their own bioavailability (i.e., liver 39%, kidney 97%, heart 37%, lung 18%, spleen 10%, and brain 72%), where plasma was 46%. These results highly suggested that different Se distribution in organs by the different route of administration was due to the different metabolic profile. (author)

  19. Tissue concentration-time profile of selenium after sodium selenite administration to rats

    International Nuclear Information System (INIS)

    Kaneko, Megumi; Natsuhori, Masahiro; Ito, Nobuhiko; Sera, Koichiro; Futatsugawa, Shoji

    1999-01-01

    Selenium (Se) concentration-time profiles in plasma and organs including liver, kidney, heart, lung, spleen and brain of rats (Jcl Wister, 9 wks old, n=32) were investigated after a single intravenous (iv) / oral (po) administration of sodium selenite (dose is equivalent to 2 mg/kg b.w. of Se). The Se concentration was determined by PIXE analysis. Among the investigated biological samples, Se concentration was the highest in the kidney or liver, followed by the heart, lung or spleen, then plasma, and the brain. Se concentrations in these organs were 0.5 to 5 times of plasma Se. The distribution profiles of Se in the organs were dependent on the route of administration. Furthermore, their profiles appeared almost parallel to the plasma Se-concentration in a logarithmic scale. Compared to the Se concentration-time profiles in plasma and organs by the route of administration, po group showed about 1/4-1/2 of the Se concentration in iv group except for kidney. Kidney kept relatively higher concentration of Se, which was similar in the both groups. This may explain our recently published data that urinary excretion was similar in the both groups. The relative oral bioavailability of plasma and each organ was calculated by the ratio of area under the concentration-time curve after oral administration (AUCpo) to AUCiv. Each organ appeared to have their own bioavailability (i.e., liver 39%, kidney 97%, heart 37%, lung 18%, spleen 10%, and brain 72%), where plasma was 46%. These results highly suggested that different Se distribution in organs by the different route of administration was due to the different metabolic profile. (author)

  20. Translocation of radiocesium from stems and leaves of plants and the effect on radiocesium concentrations in newly emerged plant tissues

    International Nuclear Information System (INIS)

    Tagami, Keiko; Uchida, Shigeo; Ishii, Nobuyoshi; Kagiya, Shigeo

    2012-01-01

    An accident occurred at the Fukushima Dai-ichi Nuclear Power Plant in March 2011 at which time large amounts of radionuclides were released into the atmosphere and the sea. In early May 2011, it was found that newly emerged tea (Camellia sinensis) leaves contained radiocesium, both 134 Cs and 137 Cs in some areas more than 300 km away from the Fukushima plant. To understand the mechanisms of radiocesium transfer to newly emerged tissues (shoots, leaves and fruits) of other plants in the future, radiocesium concentrations in newly emerged leaves of 14 plant species collected from the sampling areas in and near National Institute of Radiological Sciences in Chiba, Japan. The studied plant types were: (1) herbaceous plants, (2) woody plants with no old leaves at the time of the March accident, and (3) woody plants with old leaves out before the accident. About 40–50 d after the start of the accident, newly emerged leaves from woody plant with old leaves tended to show higher values than other woody or herbaceous plants. Concentrations of radiocesium in newly emerged tissues of trees decreased with time, but they did not decrease to the level of herbaceous plants. The type of the plant and presence of old leaves at the time of the heavy deposition period affected the radiocesium concentrations in newly emerged tissues.

  1. Effects of Weight Loss and Exercise on Apelin Serum Concentrations and Adipose Tissue Expression in Human Obesity

    Directory of Open Access Journals (Sweden)

    Joanna Krist

    2013-02-01

    Full Text Available Objective: Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases. Here we investigate the role of omental and subcutaneous (SC adipose tissue apelin and its receptor APJ mRNA expression in human obesity and test the hypothesis that changes in circulating apelin are associated with reduced fat mass in three weight loss intervention studies. Methods: Apelin serum concentration was measured in 740 individuals in a cross-sectional (n = 629 study including a subgroup (n = 161 for which omental and SC apelin mRNA expression has been analyzed and in three interventions: 12 weeks exercise (n = 60, 6 months calorie-restricted diet (n = 19, 12 months after bariatric surgery (n = 32. Results: Apelin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes and correlates with circulating apelin, BMI, body fat, C-reactive protein, and insulin sensitivity. Obesity surgery-induced weight loss causes a significant reduction in omental and SC apelin expression. All interventions led to significantly reduced apelin serum concentrations which significantly correlate with improved insulin sensitivity, independently of changes in BMI. Conclusions: Reduced apelin expression and serum concentration may contribute to improved insulin sensitivity beyond significant weight loss.

  2. Radioenzymatic assay for measurement of tissue concentrations of histamine: adaptation to correct for adherence of histamine to mechanical homogenizers

    International Nuclear Information System (INIS)

    Brown, J.K.; Frey, M.J.; Reed, B.R.; Leff, A.R.; Shields, R.; Gold, W.M.

    1984-01-01

    Because adherence of histamine to glass is well-known, we tested for its adherence to a mechanical homogenizer commonly used in the extraction of histamine from tissue samples. During 60 sec of homogenization, 15% to 17% of the histamine originally present in the samples ''disappeared,'' and the reason for the disappearance was reversible binding of histamine to the homogenizer. Adding trace amounts of [ 14 C]histamine to each sample before homogenization and measuring the disappearance of radioactivity during homogenization permitted correction for binding to the homogenizer. This technique for correction was validated by the measurement of endogenous concentrations of histamine in the tracheal posterior membranes of six dogs (range of mean concentrations: 0.63 to 1.51 ng/mg wet weight) followed by the measurement of known amounts of exogenous histamine added before homogenization to tracheal tissue samples from the same dogs. In the latter samples, 96 +/- 13% (mean +/- SEM) of the histamine added was measured by our technique. We conclude that binding of histamine to mechanical homogenizers may be an important cause of inaccuracy of the enzymatic assay for the measurement of histamine concentrations in tissue but that such binding may but that such binding may be easily corrected for

  3. Age-related effect on the concentration of collagen crosslinks in human osteonal and interstitial bone tissue.

    Science.gov (United States)

    Nyman, Jeffry S; Roy, Anuradha; Acuna, Rae L; Gayle, Heather J; Reyes, Michael J; Tyler, Jerrod H; Dean, David D; Wang, Xiaodu

    2006-12-01

    Collagen crosslinks are important to the quality of bone and may be contributors to the age-related increase in bone fracture. This study was performed to investigate whether age and gender effects on collagen crosslinks are similar in osteonal and interstitial bone tissues. Forty human cadaveric femurs were collected and divided into two age groups: middle-aged (42-63 years of age) and elderly (69-90 years of age) with ten males and ten females in each group (n = 10). Micro-cores of bone tissue from both secondary osteons and interstitial regions in the medial quadrant of the diaphysis were extracted using a custom-modified, computer-controlled milling machine. The bone specimens were then analyzed using high performance liquid chromatography to determine the effects of age and gender on the concentration of mature, enzymatic crosslinks (hydroxylysyl-pyridinoline-HP and lysyl-pyridinoline-LP) and a non-enzymatic crosslink (pentosidine-PE) at these two microstructural sites. The results indicate that age has a significant effect on the concentration of LP and PE, while gender has a significant effect on HP and LP. In addition, the concentration of the crosslinks in the secondary osteons is significantly different from that in the interstitial bone regions. These results suggest that the amount of non-enzymatic crosslinking may increase while that of mature enzymatic crosslinking may decrease with age. Such changes could potentially reduce the inherent quality of the bone tissue in the elderly skeleton.

  4. Relationships of mercury concentrations across tissue types, muscle regions and fins for two shark species

    KAUST Repository

    O'Bryhim, Jason R.; Adams, Douglas H.; Spaet, Julia L.; Mills, Gary; Lance, Stacey L.

    2017-01-01

    mercury (THg) concentrations from eight muscle regions, four fins (first dorsal, left and right pectorals, caudal-from both the inner core and trailing margin of each fin), and five internal organs (liver, kidney, spleen, heart, epigonal organ) from two

  5. Determination of bone and tissue concentrations of teicoplanin mixed with hydroxyapatite cement to repair cortical defects.

    Science.gov (United States)

    Eggenreich, K; Zeipper, U; Schwendenwein, E; Hadju, S; Kaltenecker, G; Laslo, I; Lang, S; Roschger, P; Vecsei, V; Wintersteiger, R

    2002-01-01

    A highly specific and sensitive isocratic reversed-phase high performance liquid chromatography (HPLC) method for the determination of the major component of teicoplanin in tissue is reported. Comparing fluorescamine and o-phthalaldehyde (OPA) as derivatizing agents, the derivative formed with the latter exhibits superior fluorescence intensity allowing detection of femtomole quantities. Pretreatment for tissue samples is by solid-phase extraction which uses Bakerbond PolarP C(18) cartridges and gives effective clean up from endogenous by-products. Linearity was given from 0.6 to 100 ng per injection. The coefficient of variation did not exceed 5.8% for both interday and intraday assays. It was found that when bone defects are repaired with a hydroxyapatite-teicoplanin mixture, the antibiotic does not degrade, even when it is in the cement for several months. The stability of teicoplanin in bone cement was determined fluorodensitometrically.

  6. A method for the determination of potassium concentration in organic tissue samples

    International Nuclear Information System (INIS)

    Maciel, A.C.A.

    1976-12-01

    An original method has been developed to detect small variations of potassium in several samples of organic tissue. These variations are relative to elements that are biologically representative, such as carbon, oxygen, and nitrogen. The samples are irradiated with a beam of protons from a Van de Graaff accelerator (4MV). Vacancies are created in the K-shell of potassium, and x-rays are emitted when these vacancies are filled with outer electrons. These X-rays and the protons elastically scattered by the nuclei of carbon, nitrogen and oxygen are detected and their energy spectra are analysed by computer programs especially elaborated for this purpose. A technique for routine preparation of samples in the laboratory was developed including the production of aluminum support layers, and the preparation of organic tissue samples with a low temperature microtome. The unique features of this method are that it does not destroy the tissue, permitting further analysis with the microscope, and the normalization of the amount of potassium using other elements (C,O,N) instead of the total mass of the sample. (Author) [pt

  7. Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.

    Science.gov (United States)

    Peters, Sheila Annie

    2008-01-01

    Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the

  8. Minor rheumatology: Nonsystemic rheumatic disease of juxta-articular soft tissues of the upper extremity. Part 2. Drug and non-drug treatments

    Directory of Open Access Journals (Sweden)

    Andrei Evgenyevich Karateev

    2015-01-01

    Full Text Available The treatment of rheumatic diseases of juxta-articular soft tissues (RDJAST of the upper extremity (rotator cuff tendinitis, epicondylitis, de Quervain’s syndrome, trigger finger, carpal tunnel syndrome entails a combination of drug and nondrug therapies. The basic agents that have been proven to be efficacious in this pathology are nonsteroidal anti-inflammatory drugs (NSAIDs and glucocorticosteroids (GCs. The paper considers the largest and known studies that are an evidence base for the expediency of using agents, such NSAIDs, local administration of GCs, hyaluronic acid, and plateletrich plasma, as well as different non-drug treatments, in RDJAST. The latter (physiotherapy, exercises, and rehabilitation programs should be regarded as a necessary component of the therapeutic process in patients with RDJAST-associated chronic pain. Preservation of obvious pain and impaired function despite medical therapy should be regarded as an indication for surgical treatment.

  9. Tissue concentrations of four Taiwanese toothed cetaceans indicating the silver and cadmium pollution in the western Pacific Ocean.

    Science.gov (United States)

    Chen, Meng-Hsien; Zhuang, Ming-Feng; Chou, Lien-Siang; Liu, Jean-Yi; Shih, Chieh-Chih; Chen, Chiee-Young

    2017-11-30

    Muscle, lung, kidney and liver tissues of 45 bycatch and stranded cetaceans, including 14 Grampus griseus (Gg), 7 Kogia simus (Ks), 10 Lagenodelphis hosei (Lh), and 14 Stenella attenuata (Sa), were collected in the waters off Taiwan from 1994 to 1995, and from 2001 to 2012. Baseline concentrations (in μgg -1 dry weight) of the cetaceans were lung (<0.05)=muscle (<0.05)tissue concentrations in the toothed cetaceans are suggested. Marked high concentrations of Ag and Cd found in Gg and Lh are highly related to their squid-eating and deep diving habits. The highest ever recorded concentrations of liver-Ag and kidney-Cd were found in two Lh. These Taiwanese cetaceans indicate marked Ag and Cd pollution in the recent two decades in the western Pacific Ocean. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Heavy metal concentrations in gill and liver tissues of Rutilus kutum and Chelon aurata in the coast of Babolsar, southern Caspian Sea

    Directory of Open Access Journals (Sweden)

    Fatemeh Kardel

    2016-04-01

    Full Text Available Heavy metal accumulation in the aquatic ecosystems is a main concern which threats human health. In this study two commercial fish species, Rutilus kutum and Chelon aurata were selected for assessing heavy metal (Cd, Pb, Zn concentrations in gill and liver tissues at Babolsar’s coast, the southern Caspian Sea, Iran. Babolsar is one of the important fishery stations in the southern Caspian Sea. The results showed that liver tissue of C. aurata significantly accumulated higher concentration of Cd, Pb and Zn compared to that of R. kutum, but these results were not significant for gill tissue. Liver tissue accumulated higher concentration of Cd and Pb compared to gill tissue in C. aurata, but these results were not significant for R. kutum. It is concluded that the liver tissue of C. aurata has higher potential to accumulate heavy metal pollution compared to liver tissue of R. kutum

  11. Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests.

    Science.gov (United States)

    Swaminathan, Soumya; Pasipanodya, Jotam G; Ramachandran, Geetha; Hemanth Kumar, A K; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

    2016-11-01

     The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown.  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables.  Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28-5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08-4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99-11.82).  We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations

    NARCIS (Netherlands)

    Lempers, V.J.C.; Alffenaar, J.W.C.; Touw, D.J.; Burger, D.M.; Uges, D.R.A.; Aarnoutse, R.E.; Brüggemann, R.J.M.

    2014-01-01

    OBJECTIVES: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.

  13. Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation.

    Science.gov (United States)

    Anselmo, Aaron C; Gilbert, Jonathan B; Kumar, Sunny; Gupta, Vivek; Cohen, Robert E; Rubner, Michael F; Mitragotri, Samir

    2015-02-10

    Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Folate coupled poly(ethyleneglycol) conjugates of anionic poly(amidoamine) dendrimer for inflammatory tissue specific drug delivery.

    Science.gov (United States)

    Chandrasekar, Durairaj; Sistla, Ramakrishna; Ahmad, Farhan J; Khar, Roop K; Diwan, Prakash V

    2007-07-01

    Folate receptor is overexpressed on the activated (but not quiescent) macrophages in both animal models and human patients with naturally occurring rheumatoid arthritis. The aim of this study was to prepare folate targeted poly(ethylene glycol) (PEG) conjugates of anionic dendrimer (G3.5 PAMAM) as targeted drug delivery systems to inflammation and to investigate its biodistribution pattern in arthritic rats. Folate-PEG-PAMAM conjugates, with different degrees of substitution were synthesized by a two-step reaction through a carbodiimide-mediated coupling reaction and loaded with indomethacin. Folate-PEG conjugation increased the drug loading efficiency by 10- to 20-fold and the in vitro release profile indicated controlled release of drug. The plasma pharmacokinetic parameters indicated an increased AUC, circulatory half-life and mean residence time for the folate-PEG conjugates. The tissue distribution studies revealed significantly lesser uptake by stomach for the folate-PEG conjugates, thereby limiting gastric-related side effect. The time-averaged relative drug exposure (r(e)) of the drug in paw for the folate-PEG conjugates ranged from 1.81 to 2.37. The overall drug targeting efficiency (T(e)) was highest for folate-PEG conjugate (3.44) when compared to native dendrimer (1.72). The folate-PEG-PAMAM conjugates are the ideal choice for targeted delivery of antiarthritic drugs to inflammation with reduced side-effects and higher targeting efficiency. Copyright 2007 Wiley Periodicals, Inc.

  15. Modified n-HA/PA66 scaffolds with chitosan coating for bone tissue engineering: cell stimulation and drug release.

    Science.gov (United States)

    Zou, Qin; Li, Junfeng; Niu, Lulu; Zuo, Yi; Li, Jidong; Li, Yubao

    2017-09-01

    The dipping-drying procedure and cross-linking method were used to make drug-loaded chitosan (CS) coating on nano-hydroxyapatite/polyamide66 (nHA/PA66) composite porous scaffold, endowing the scaffold controlled drug release functionality. The prefabricated scaffold was immersed into an aqueous drug/CS solution in a vacuum condition and then crosslinked by vanillin. The structure, porosity, composition, compressive strength, swelling ratio, drug release and cytocompatibility of the pristine and coating scaffolds were investigated. After coating, the scaffold porosity and pore interconnection were slightly decreased. Cytocompatibility performance was observed through an in vitro experiment based on cell attachment and the MTT assay by MG63 cells which revealed positive cell viability and increasing proliferation over the 11-day period in vitro. The drug could effectively release from the coated scaffold in a controlled fashion and the release rate was sustained for a long period and highly dependent on coating swelling, suggesting the possibility of a controlled drug release. Our results demonstrate that the scaffold with drug-loaded crosslinked CS coating can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to be a promising high performance biomaterial in bone tissue engineering.

  16. Relationship between serum adiponectin concentration, body condition score, and peripheral tissue insulin response of dairy cows during the dry period.

    Science.gov (United States)

    De Koster, J; Urh, C; Hostens, M; Van den Broeck, W; Sauerwein, H; Opsomer, G

    2017-04-01

    The aim of the present study was to describe the relationship between serum adiponectin concentration and peripheral tissue insulin response in dairy cows with a variable body condition score (BCS) during the dry period. Cows were selected at the beginning of the dry period based on BCS (BCS 3.75, n = 5). Animals were followed from the beginning of the dry period by weekly blood sampling and assessment of BCS and backfat thickness. Weekly blood samples were analyzed for adiponectin concentration using a bovine specific ELISA. Hyperinsulinemic euglycemic clamp tests were performed at the end of the dry period to measure peripheral tissue insulin response. Insulin dose response curves were established for both glucose and fatty acid metabolism. Regression analysis revealed that the serum concentrations of adiponectin dropped at the end of the dry period (P insulin responsiveness (reflecting the maximal effect of insulin; r = 0.76, P insulin sensitivity (reflecting the insulin concentration needed to achieve halfmaximal effect; r = -0.54, P = 0.13). At the level of the fatty acid metabolism, greater adiponectin concentrations were negatively correlated with lower NEFA levels during the HEC test reflecting the insulin responsiveness of the NEFA metabolism (r = -0.61, P = 0.08), whereas there was no association with the insulin sensitivity of the NEFA metabolism (r = -0.16, P = 0.67). In conclusion, serum concentrations of adiponectin were negatively associated with the BCS of dairy cows during the dry period and positively associated with insulin responsiveness of the glucose and fatty acid metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Concentration of Potassium in Plasma, Erythrocytes, and Muscle Tissue in Cows with Decreased Feed Intake and Gastrointestinal Ileus.

    Science.gov (United States)

    Schneider, S; Müller, A; Wittek, T

    2016-01-01

    Healthy cows consume large amounts of potassium and a sudden loss in appetite can lead to hypokalemia. The routine method to evaluate potassium homeostasis is the measurement of the extracellular potassium in plasma or serum, but this does not provide information about the intracellular potassium pool. To evaluate potassium homeostasis by comparing the extracellular and intracellular potassium concentration in cows with reduced feed intake and gastrointestinal ileus. Twenty cows 1-3 days postpartum (group 1) and 20 cows with gastrointestinal ileus (group 2). Observational cross-sectional study. Plasma potassium was measured by using an ion-sensitive electrode. Intracellular potassium was measured in erythrocytes and muscle tissue (muscle biopsy) by using inductively coupled plasma optical emission spectroscopy. Cows of group 1 did not have hypokalemia. Overall cows with gastrointestinal ileus were hypokalemic (mean ± SD, 2.9 mmol/L ± 0.78), but potassium concentration in erythrocytes and muscle tissue was not lower than in postpartum cows. Intracellular potassium in erythrocytes varied very widely; group 1: 3497-10735 mg/kg (5559 ± 2002 mg/kg), group 2: 4139-21678 mg/kg (7473 ± 4034 mg/kg). Potassium in muscle tissue did not differ between group 1 (3356 ± 735 mg/kg wet weight) and group 2 (3407 ± 1069 mg/kg wet weight). No association between extracellular and intracellular potassium concentrations was detected. That measurement of plasma potassium concentration is not sufficient to evaluate potassium metabolism of cows. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. Concentration of folate in colorectal tissue biopsies predicts prevalence of adenomatous polyps

    Science.gov (United States)

    Background and aims: Folate has been implicated as a potential aetiological factor for colorectal cancer. Previous research has not adequately exploited concentrations of folate in normal colonic mucosal biopsies to examine the issue. Methods: Logistic regression models were used to estimate ORs ...

  19. Heavy metal concentration in different tissues of fishes from coastal waters of Cochin

    Digital Repository Service at National Institute of Oceanography (India)

    Nair, M.; Balachandran, K.K.; Sankaranarayanan, V.N.; Joseph, T.

    Information on the concentration of trace metals in the environment is essential to assess the possible accumulation of these metals in the body of organisms and its transfer to man through the food chain. Muscles, alimentary canal and gills of 14...

  20. Regulating NH4+, N0-, and K+ concentration and proportions improves in vitro tissue growth.

    Science.gov (United States)

    A mixture-amount experiment that simultaneously varied both the ratios and total ionic concentration (from 20-100 mM) of NH4+, NO3+, and K+ was used to maximize sweet orange callus growth cv. ‘Hamlin.’ These experiments were free of ion confounding effects, i.e. ions added via pH adjustments and sa...

  1. Use and abuse of trace metal concentrations in plant tissue for biomonitoring and phytoextraction

    NARCIS (Netherlands)

    Mertens, Jan; Luyssaert, Sebastiaan; Verheyen, Kris

    2005-01-01

    Some plant species accumulate trace metals from the soil in their aboveground biomass. Therefore, some scientists have concluded that these species are suitable for biomonitoring trace metal concentrations in the soil or for removing excessive trace metals from the soil by means of phytoextraction.

  2. The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation

    NARCIS (Netherlands)

    T.R.H. Regnault (Timothy); C. Teng (Cecilia); B. de Vrijer (Barbra); H.L. Galan (Henry); R.B. Wilkening (Randall); F.C. Battaglia (Frederick)

    2010-01-01

    textabstractIn an ovine model of placental insufficiency-induced intrauterine growth retardation (PI-IUGR), characterized by hypoxia, hypoglycemia and a significant reduction in fetal weight, we assessed alterations in fetal and placental polyols. Arterial maternal-fetal concentration differences of

  3. Evaluation of Metal Ion Concentration in Hard Tissues of Teeth in Residents of Central Poland

    Directory of Open Access Journals (Sweden)

    Piotr Wychowanski

    2017-01-01

    Full Text Available Objectives. The aim of the study was an assessment of the content of trace elements in enamel and dentin of teeth extracted in patients residing in urban and agricultural areas of Poland. Methods. The study included 30 generally healthy patients with retained third molars. 65 samples of enamel and dentin from individuals living in urban areas and 85 samples of enamel and dentin from individuals living in agricultural areas were prepared. The content of manganese, lead, cadmium, and chromium in the studied enamel and dentin samples from retained teeth was determined by Graphite Furnace Atomic Absorption Spectrometry. In the process of statistical hypothesis testing, the level of significance was assumed at α=0.05. Results. A comparative analysis of the data showed that enamel and dentin of inhabitants of industrialized areas contain significantly higher amounts of lead and cadmium than hard tissues of teeth in residents of agricultural areas and comparable amounts of manganese and chromium. Significance. It appears that hard tissues of retained teeth may constitute valuable material for assessment of long-term environmental exposure to metal ions. The study confirms that the risk of exposure to heavy metals depends on the place of residence and environmental pollution.

  4. Tissue lead concentration during chronic exposure of Pimephales promelas (fathead minnow) to lead nitrate in aquarium water.

    Science.gov (United States)

    Spokas, Eric G; Spur, Bernd W; Smith, Holly; Kemp, Francis W; Bogden, John D

    2006-11-01

    The fathead minnow is a useful species for evaluating the toxicity of wastewater effluents. While this fish is widely used for "survival" studies of metal toxicity, little or no work has been done on the tissue distribution of metals in fathead minnows. To determine the distribution of tissue lead, aquarium studies were conducted for several weeks with fish maintained in soft synthetic freshwater. Lead- (II) nitrate was added to three aquaria attaining concentrations of 20-30 ppb (aquarium B), 100-140 ppb (aquarium C), and roughly 200 ppb (aquarium D). Results were compared to controls (aquarium A). During the initial week, the majority of aquarium D fish died, whereas few deaths occurred in the other groups. Lead accumulation was dose- and tissue-dependent, with highest uptake by the gills. Gill concentrations of aquarium D fish averaged about 4-fold higherthan in skeleton or skin and muscle. In vitro, lead (2.5-25 ppm) caused dose-dependent reductions in the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) in gills incubated in physiological buffer. These findings demonstrate that fathead minnow gills bind and accumulate waterborne lead rapidly and preferentially and raise the possibility that gill lipid peroxidation contributes to lead toxicity at low water hardness.

  5. Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

    Science.gov (United States)

    Palmer, Brian C.; DeLouise, Lisa A.

    2017-01-01

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

  6. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

    Science.gov (United States)

    Palmer, Brian C; DeLouise, Lisa A

    2016-12-15

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  7. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

    Directory of Open Access Journals (Sweden)

    Brian C. Palmer

    2016-12-01

    Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  8. Intracellular co-delivery of Sr ion and phenamil drug through mesoporous bioglass nanocarriers synergizes BMP signaling and tissue mineralization.

    Science.gov (United States)

    Lee, Jung-Hwan; Mandakhbayar, Nandin; El-Fiqi, Ahmed; Kim, Hae-Won

    2017-09-15

    Inducing differentiation and maturation of resident multipotent stem cells (MSCs) is an important strategy to regenerate hard tissues in mal-calcification conditions. Here we explore a co-delivery approach of therapeutic molecules comprised of ion and drug through a mesoporous bioglass nanoparticle (MBN) for this purpose. Recently, MBN has offered unique potential as a nanocarrier for hard tissues, in terms of high mesoporosity, bone bioactivity (and possibly degradability), tunable delivery of biomolecules, and ionic modification. Herein Sr ion is structurally doped to MBN while drug Phenamil is externally loaded as a small molecule activator of BMP signaling, for the stimulation of osteo/odontogenesis and mineralization of human MSCs derived from dental pulp. The Sr-doped MBN (85Si:10Ca:5Sr) sol-gel processed presents a high mesoporosity with a pore size of ∼6nm. In particular, Sr ion is released slowly at a daily rate of ∼3ppm per mg nanoparticles for up to 7days, a level therapeutically effective for cellular stimulation. The Sr-MBN is internalized to most MSCs via an ATP dependent macropinocytosis within hours, increasing the intracellular levels of Sr, Ca and Si ions. Phenamil is loaded maximally ∼30% into Sr-MBN and then released slowly for up to 7days. The co-delivered molecules (Sr ion and Phenamil drug) have profound effects on the differentiation and maturation of cells, i.e., significantly enhancing expression of osteo/odontogenic genes, alkaline phosphatase activity, and mineralization of cells. Of note, the stimulation is a result of a synergism of Sr and Phenamil, through a Trb3-dependent BMP signaling pathway. This biological synergism is further evidenced in vivo in a mal-calcification condition involving an extracted tooth implantation in dorsal subcutaneous tissues of rats. Six weeks post operation evidences the osseous-dentinal hard tissue formation, which is significantly stimulated by the Sr/Phenamil delivery, based on histomorphometric

  9. Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat

    OpenAIRE

    Scollon, Edward J.; Starr, James M.; Crofton, Kevin M.; Wolansky, Marcelo J.; DeVito, Michael J.; Hughes, Michael F.

    2011-01-01

    The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1 h at 4- and 7-h following exposure to bifenthrin (0–16 mg/kg or 0...

  10. Polychlorinated biphenyl concentrations in adipose tissue as determinants of abdominal obesity in the Elderly

    DEFF Research Database (Denmark)

    Bräuner, Elvira; Raaschou-Nielsen, Ole; Andersen, Zorana

    2013-01-01

    Obesity prevalence has more than doubled globally within the last 30 years and obesity affects quality of life as well as impacts the risks and prognosis for a number of serious diseases. Established causes include a high calorie diet combined with a sedentary lifestyle, but these do not fully...... explain the epidemic. Evidence from animal experiments suggests that exposure to endocrine disruptors such as PCBs is associated with the development of obesity but our knowledge of the effects of these compounds on weight gain in humans is limited. Our objective was to investigate the association between...... exposure to PCBs experienced by a general Danish population and abdominal obesity. Adipose tissue was collected upon enrolment of 245 randomly selected persons from a prospective cohort of 57,053 persons enrolled between 1993 and 1997. Abdominal obesity was quantified using self-reported waist...

  11. A non-invasive diffuse reflectance calibration-free method for absolute determination of exogenous biochemicals concentration in biological tissues

    Science.gov (United States)

    Lappa, Alexander V.; Kulikovskiy, Artem N.; Busarov, Oleg G.

    2014-03-01

    The paper presents a new method for distant non-destructive determination of concentration of light absorbing admixtures in turbid media. In particular, it is intended for non-invasive in vivo control of accumulation in patient tissues of various biochemicals introduced to the patients for chemotherapy, photodynamic therapy or diagnostics. It is require that the admixture absorption spectrum should have a clearly marked peak in the wavelength region where the pure medium one varies regularly. Fluorescence of admixtures is not required. The method uses the local diffuse reflectance spectroscopy with optical fiber probe including one emitting and two reading There are several features in the method: the value to be determined is absolute concentration of admixtures; the method needs no calibration measurements on phantoms; it needs no reference measurements on sample with zero admixture concentration; it uses a two parametric kinetic light propagation model and original algorithms to resolve direct and inverse tasks of radiation transport theory. Experimental testing passed with tissue equivalent phantoms and different admixtures, including a chlorine photosensitizer, showed accuracy under 10% in all cases.

  12. Concentration change of DA, DOPAC, Glu and GABA in brain tissues in schizophrenia developmental model rats induced by MK-801.

    Science.gov (United States)

    Liu, Yong; Tang, Yamei; Pu, Weidan; Zhang, Xianghui; Zhao, Jingping

    2011-08-01

    To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA), dihydroxy-phenyl acetic acid (DOPAC), glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats. A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6: an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10, 0.1 mg/kg, Bid), a chronic medication model group (intraperitoneal injection at the postnatal day 47-60, 0.2 mg/kg,Qd), and a normal control group (injection with 0.9% normal saline during the corresponding periods). DA, DOPAC, Glu, and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique. The utilization rate of DA and Glu was calculated. Compared with the normal control group, the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased (PGABA concentration and Glu utilization rate in the mPFC also decreased (PGABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.

  13. {sup 226}Ra concentrations in crayfish tissues, water, and sediments from the Serpent River Basin in Northeastern Ontario, Canada

    Energy Technology Data Exchange (ETDEWEB)

    Alikhan, M.A. [Laurentian Univ., Sudbury, ON (Canada). Dept of Biology

    1996-12-31

    Lower Serpent River, as well as Elliot, McCarthy and McCabe lakes had highest {sup 226}Ra contamination, Chrisman, Quirke and Whiskey lakes a moderate one, Flack and Semiwhite lakes and the `distant` control, Lake Wanapitei, the lowest. {sup 226}Ra activity in Cambarus robustus tissues was directly related to their background levels. Thus, concentration coefficient (tissue/sediment concentrations) for {sup 226}Ra ranged from 0.53 to 0.74 in highly contaminated Elliot and McCarthy lakes, 0.28 to 0.59 in moderately contaminated Quirke and Whiskey lakes, and from 0.27 to 3.44 in least contaminated Semiwhite and Flack lakes. Among various organs analysed, exoskeleton showed the highest (43.04 - 90.69%) and the tail muscles the lowest (2.95 -17.14%) {sup 226}Ra activity. {sup 226}Ra concentrations in the alimentary canal were considered a part of the ambient environment as they had not been absorbed. 12 refs, 1 fig, 1 tab.

  14. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

    OpenAIRE

    Lionberger, David

    2010-01-01

    David R Lionberger1, Michael J Brennan21Southwest Orthopedic Group, Houston, TX, USA; 2Department of Medicine, Bridgeport Hospital, Bridgeport, CT, USAAbstract: The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with ac...

  15. Drug intercalation in layered double hydroxide clay: Application in the development of a nanocomposite film for guided tissue regeneration

    DEFF Research Database (Denmark)

    Chakraborti, M.; Jackson, J.K.; Plackett, David

    2011-01-01

    It has been proposed that localized and controlled delivery of alendronate and tetracycline to periodontal pocket fluids via guided tissue regeneration (GTR) membranes may be a valuable adjunctive treatment for advanced periodontitis. The objectives of this work were to develop a co...... evidence of intercalation in the LDH clay particles. The dual drug loaded nanocomposite films were biocompatible with osteoblasts and after 5 week incubations, significant increase in alkaline phosphatase activity and bone nodule formation were observed....

  16. Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden.

    Science.gov (United States)

    Ahlner, Johan; Holmgren, Anita; Jones, Alan Wayne

    2014-03-01

    Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. The mean age of all victims (N = 895) was 48 ± 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (± SD) 47 ± 20 years, than alcohol positive cases (35 ± 14 years) and illicit drug users (34 ± 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in ~7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.

  17. Biocompatible nanocomposite scaffolds based on copolymer-grafted chitosan for bone tissue engineering with drug delivery capability

    International Nuclear Information System (INIS)

    Saber-Samandari, Samaneh; Saber-Samandari, Saeed

    2017-01-01

    Significant efforts have been made to develop a suitable biocompatible scaffold for bone tissue engineering. In this work, a chitosan-graft-poly(acrylic acid-co-acrylamide)/hydroxyapatite nanocomposite scaffold was synthesized through a novel multi-step route. The prepared scaffolds were characterized for crystallinity, morphology, elemental analysis, chemical bonds, and pores size in their structure. The mechanical properties (i.e. compressive strength and elastic modulus) of the scaffolds were examined. Further, the biocompatibility of scaffolds was determined by MTT assays on HUGU cells. The result of cell culture experiments demonstrated that the prepared scaffolds have good cytocompatibility without any cytotoxicity, and with the incorporation of hydroxyapatite in their structure improves cell viability and proliferation. Finally, celecoxib as a model drug was efficiently loaded into the prepared scaffolds because of the large specific surface area. The in vitro release of the drug displayed a biphasic pattern with a low initial burst and a sustained release of up to 14 days. Furthermore, different release kinetic models were employed for the description of the release process. The results suggested that the prepared cytocompatible and non-toxic nanocomposite scaffolds might be efficient implants and drug carriers in bone-tissue engineering. - Highlights: • A series of biocompatible scaffolds were synthesized through a novel multi-step route. • The mechanical properties of the scaffolds were found close to those of trabecular bone. • The prepared scaffolds were able to load celecoxib efficiently as a model drug. • The celecoxib release was mainly controlled by a Fickian diffusion process. • The scaffold can be efficient as an implant for tissue engineering and drug delivery.

  18. Biocompatible nanocomposite scaffolds based on copolymer-grafted chitosan for bone tissue engineering with drug delivery capability

    Energy Technology Data Exchange (ETDEWEB)

    Saber-Samandari, Samaneh, E-mail: samaneh.saber@gmail.com [Department of Chemistry, Eastern Mediterranean University, Gazimagusa, TRNC via Mersin 10 (Turkey); Saber-Samandari, Saeed, E-mail: saeedss@aut.ac.ir [New Technologies Research Center, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of)

    2017-06-01

    Significant efforts have been made to develop a suitable biocompatible scaffold for bone tissue engineering. In this work, a chitosan-graft-poly(acrylic acid-co-acrylamide)/hydroxyapatite nanocomposite scaffold was synthesized through a novel multi-step route. The prepared scaffolds were characterized for crystallinity, morphology, elemental analysis, chemical bonds, and pores size in their structure. The mechanical properties (i.e. compressive strength and elastic modulus) of the scaffolds were examined. Further, the biocompatibility of scaffolds was determined by MTT assays on HUGU cells. The result of cell culture experiments demonstrated that the prepared scaffolds have good cytocompatibility without any cytotoxicity, and with the incorporation of hydroxyapatite in their structure improves cell viability and proliferation. Finally, celecoxib as a model drug was efficiently loaded into the prepared scaffolds because of the large specific surface area. The in vitro release of the drug displayed a biphasic pattern with a low initial burst and a sustained release of up to 14 days. Furthermore, different release kinetic models were employed for the description of the release process. The results suggested that the prepared cytocompatible and non-toxic nanocomposite scaffolds might be efficient implants and drug carriers in bone-tissue engineering. - Highlights: • A series of biocompatible scaffolds were synthesized through a novel multi-step route. • The mechanical properties of the scaffolds were found close to those of trabecular bone. • The prepared scaffolds were able to load celecoxib efficiently as a model drug. • The celecoxib release was mainly controlled by a Fickian diffusion process. • The scaffold can be efficient as an implant for tissue engineering and drug delivery.

  19. Recent progress in the synthesis of poly(organo)phosphazenes and their applications in tissue engineering and drug delivery

    Science.gov (United States)

    Khan, R. U.; Wang, L.; Yu, H.; Zain-ul-Abdin; Akram, M.; Wu, J.; Haroon, M.; Ullah, R. S.; Deng, Zh; Xia, X.

    2018-02-01

    It is a highly desirable goal of researchers to develop effective biomaterials with minimum recovery time and affordable treatment expense for tissue engineering and drug delivery. In this scenario, numerous synthetic and natural polymers have been used. Among those synthetic polymers, polyorganophosphazenes (POPs) have got much attention as highly promising candidates for applications in tissue engineering and drug delivery. Polyorganophosphazenes are hybrid polymers containing inorganic backbone consisting of alternating nitrogen and phosphorus atoms with two organic side groups. POPs possess a wide range of unique properties, i.e., synthetic flexibility, biocompatibility, osteocompatibility, osteoinductivity, sustainability and degradability into harmless end products with predictable degradation rate and adjustable mechanical strength. Moreover, their tunable hydrophilic/hydrophobic and stimuli responsive properties add extra points to their use in biomedical applications. In addition, their various polymeric forms, i.e., microspheres, nano/microfibres, micelles, membranes, polymersomes, hydrogels and nano-conjugate linear polymers provide different carriers to efficiently deliver various hydrophilic/hydrophobic therapeutic agents both in vitro and in vivo. This review focuses on the most recent progress that has been made in the synthesis and applications of POPs in tissue engineering and their different polymeric forms used for drug delivery. Moreover, we have also summarized the effect of different side groups on the overall efficiency of POPs. The bibliography includes 239 references.

  20. ORION: a computer code for evaluating environmental concentrations and dose equivalent to human organs or tissue from airborne radionuclides

    International Nuclear Information System (INIS)

    Shinohara, K.; Nomura, T.; Iwai, M.

    1983-05-01

    The computer code ORION has been developed to evaluate the environmental concentrations and the dose equivalent to human organs or tissue from air-borne radionuclides released from multiple nuclear installations. The modified Gaussian plume model is applied to calculate the dispersion of the radionuclide. Gravitational settling, dry deposition, precipitation scavenging and radioactive decay are considered to be the causes of depletion and deposition on the ground or on vegetation. ORION is written in the FORTRAN IV language and can be run on IBM 360, 370, 303X, 43XX and FACOM M-series computers. 8 references, 6 tables

  1. Machine Learning of Human Pluripotent Stem Cell-Derived Engineered Cardiac Tissue Contractility for Automated Drug Classification

    Directory of Open Access Journals (Sweden)

    Eugene K. Lee

    2017-11-01

    Full Text Available Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a daunting challenge. Immense research effort has been focused toward creating new screening platforms that utilize human pluripotent stem cell (hPSC-derived cardiomyocytes and three-dimensional engineered cardiac tissue constructs to better recapitulate human heart function and drug responses. As these new platforms become increasingly sophisticated and high throughput, the drug screens result in larger multidimensional datasets. Improved automated analysis methods must therefore be developed in parallel to fully comprehend the cellular response across a multidimensional parameter space. Here, we describe the use of machine learning to comprehensively analyze 17 functional parameters derived from force readouts of hPSC-derived ventricular cardiac tissue strips (hvCTS electrically paced at a range of frequencies and exposed to a library of compounds. A generated metric is effective for then determining the cardioactivity of a given drug. Furthermore, we demonstrate a classification model that can automatically predict the mechanistic action of an unknown cardioactive drug.

  2. Investigation of the Relationship of Some Antihypertensive Drugs with Oxidant/Antioxidant Parameters and DNA Damage on Rat Uterus Tissue

    Directory of Open Access Journals (Sweden)

    Mustafa Talip Sener

    2011-01-01

    Full Text Available Background: In this study, we investigated the effects of treatment with chronic antihypertensivedrugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine on oxidant-antioxidantparameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examinedhistopathologically.Materials and Methods: A total of 36 albino Wistar rats were divided into the following six groups:0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg/kgramipril group; 0.5 mg/kg rilmenidine group; and the healthy group. Rats underwent chronic drugadministration for 30 days and at the end, biochemical and histopathological examinations wereperformed. All data were subjected to one-way ANOVA test.Results: We divided these drugs into the following three groups according to their effects on ratuteri: (I mild negative effects (clonidine, (II moderate negative effects (rilmenidine, methyldopaand (III drugs which had severe negative effects (amlodipine, ramipril.Conclusion: These data may help with selection of antihypertensive drugs, in order to determinewhich drugs have the lowest toxicity in pregnant and non-pregnant (pre-pregnancy women.

  3. Intrabronchial Microdialysis: Effects of Probe Localization on Tissue Trauma and Drug Penetration into the Pulmonary Epithelial Lining Fluid

    DEFF Research Database (Denmark)

    Rottbøll, Lisa Amanda Holm; Skovgaard, Kerstin; Barington, Kristiane

    2015-01-01

    (PELF). The objective of this study was to investigate the effect of intrabronchial microdialysis on the integrity of the bronchial epithelium. Microdialysis sampling in PELF in proximal (n=4) and distal bronchi (n=4) was performed after intravenous inulin and florfenicol administration in anaesthetized...... pigs. Inulin was used as a marker molecule of permeability of the epithelium, and florfenicol was used as test drug. Bronchial tissue was examined by histopathology (distal and proximal bronchi) and gene expression analysis (RT-qPCR, proximal bronchi) at the termination of the experiment (6.5hr....... Likewise, florfenicol penetration into PELF was unaffected by bronchial histopathology. However, this independency of pathology on drug penetration may not be valid for other antibiotics. We conclude that short-term microdialysis drug quantification can be performed in proximal bronchi without disruption...

  4. Digital photography provides a fast, reliable, and noninvasive method to estimate anthocyanin pigment concentration in reproductive and vegetative plant tissues.

    Science.gov (United States)

    Del Valle, José C; Gallardo-López, Antonio; Buide, Mª Luisa; Whittall, Justen B; Narbona, Eduardo

    2018-03-01

    anthocyanin concentrations in both floral and vegetative tissues. This method is efficient, completely noninvasive, applicable to both uniform and patterned color, and works with samples of any size.

  5. Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

    International Nuclear Information System (INIS)

    Rodrigues-Peres, Raquel Mary; Cadore, Solange; Febraio, Stefanny; Heinrich, Juliana Karina; Serra, Katia Piton; Derchain, Sophie F M; Vassallo, Jose; Sarian, Luis Otavio

    2013-01-01

    Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum

  6. Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

    Science.gov (United States)

    2013-01-01

    Background Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. Methods A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. Results The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Conclusions Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next

  7. Effects of Dietary Zinc Pectin Oligosaccharides Chelate Supplementation on Growth Performance, Nutrient Digestibility and Tissue Zinc Concentrations of Broilers.

    Science.gov (United States)

    Wang, Zhongcheng; Yu, Huimin; Wu, Xuezhuang; Zhang, Tietao; Cui, Hu; Wan, Chunmeng; Gao, Xiuhua

    2016-10-01

    The experiment was conducted to investigate the effects of zinc pectin oligosaccharides (Zn-POS) chelate on growth performance, nutrient digestibility, and tissue zinc concentrations of Arbor Acre broilers aged from 1 to 42 days. A total of 576 1-day-old broilers were randomly assigned into 4 groups with 9 replicates per group and 16 chicks per replicate. Chicks were fed either a basal diet (control) or basal diet supplemented with Zn-POS at 300 (Zn-POS-300), 600 (Zn-POS-600), or 900 mg/kg (Zn-POS-900), respectively, for 42 days. A 3-day metabolism trial was conducted during the last week of the experiment feeding. The average daily gain and the average daily feed intake of Zn-POS-600 were significantly higher (P digestibility of dry matter, crude protein, and metabolic energy among all groups. The control group had the lowest apparent digestibility of dry matter (P digestibility of dry matter in Zn-POS-600 was higher (P digestibility of crude protein in Zn-POS-600 or Zn-POS-900 was higher (P digestibility of metabolic energy in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) than that of Zn-POS-300. Zn-POS-600 had the highest liver zinc concentrations (P < 0.05), while Zn-POS-900 had the highest pancreatic zinc concentrations (P < 0.05). Our data suggest that the supplementation of 600 mg/kg Zn-POS is optimal in improving the average daily gain and the average daily feed intake, utilization of dietary dry matter and crude protein, and increasing tissue zinc concentrations in liver and pancreas of broilers.

  8. Ex vivo preparations of human tissue for drug metabolism, toxicity and transport

    NARCIS (Netherlands)

    Groothuis, Genoveva

    2012-01-01

    Before new drugs are allowed on the market, their safety and metabolite profile should be extensively tested, as often reactive metabolites are the ultimate toxicant. The exposure of the target cell to the drug and its metabolites is determined by the expression levels of the transporters and the

  9. Concentrations of 17 elements, including mercury, in the tissues, food and abiotic environment of Arctic shorebirds.

    Science.gov (United States)

    Hargreaves, Anna L; Whiteside, Douglas P; Gilchrist, Grant

    2011-09-01

    Exposure to contaminants is one hypothesis proposed to explain the global decline in shorebirds, and is also an increasing concern in the Arctic. We assessed potential contaminants (As, Be, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Se, Tl, V, and Zn) at a shorebird breeding site in Nunavut, Canada. We compared element levels in soil, invertebrates and shorebird blood to assess evidence for bioconcentration and biomagnification within the Arctic-based food chain. We tested whether elements in blood, feathers and eggs of six shorebird species (Pluvialis squatarola, Calidris alpina, C. fuscicollis, Phalaropus fulicarius, Charadrius semipalmatus, and Arenaria interpres) were related to fitness endpoints: adult body condition, blood-parasite load, egg size, eggshell thickness, nest duration, and hatching success. To facilitate comparison to other sites, we summarise the published data on toxic metals in shorebird blood and egg contents. Element concentrations and invertebrate composition differed strongly among habitats, and habitat use and element concentrations differed among shorebird species. Hg, Se, Cd, Cu, and Zn bioconcentrated from soil to invertebrates, and Hg, Se and Fe biomagnified from invertebrates to shorebird blood. As, Ni, Pb, Co and Mn showed significant biodilution from soil to invertebrates to shorebirds. Soil element levels were within Canadian guidelines, and invertebrate Hg levels were below dietary levels suggested for the protection of wildlife. However, maximum Hg in blood and eggs approached levels associated with toxicological effects and Hg-pollution in other bird species. Parental blood-Hg was negatively related to egg volume, although the relationship varied among species. No other elements approached established toxicological thresholds. In conclusion, whereas we found little evidence that exposure to elements at this site is leading to the declines of the species studied, Hg, as found elsewhere in the Canadian Arctic, is of potential

  10. Relationship between Concentrations of Lutein and StARD3 among Pediatric and Geriatric Human Brain Tissue.

    Directory of Open Access Journals (Sweden)

    Jirayu Tanprasertsuk

    Full Text Available Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and cognitive health have been poorly evaluated at a molecular level. The objective of this study was to evaluate the cross-sectional relationship between concentrations of brain lutein and StARD3 (identified as its binding protein in retinal tissue among three age groups: infants (1-4 months, n = 10, older adults (55-86 years, n = 8, and centenarians (98-105 years, n = 10. Brain lutein concentrations were analyzed by high-performance liquid chromatography and StARD3 levels were analyzed by Western Blot analysis. The strong relationship in infant brains (r = 0.75, P 0.05, seven of whom had mild cognitive impairment (MCI or dementia. These exploratory findings suggest an age-related decrease or abnormality of StARD3 activity in human brain. Given that StARD3 is also involved in cholesterol transportation, a process that is aberrant in neurodegenerative diseases, the potential protective function of lutein against these diseases remains to be explored.

  11. Spectrophotometric Method for the Determination of Two Coformulated Drugs with Highly Different Concentrations. Application on Vildagliptin and Metformin Hydrochloride

    Science.gov (United States)

    Zaazaa, H. E.; Elzanfaly, E. S.; Soudi, A. T.; Salem, M. Y.

    2016-03-01

    A new smart simple validated spectrophotometric method was developed for the determination of two drugs one of which is in a very low concentration compared to the other. The method is based on spiking and dilution then simple mathematical manipulation of the absorbance spectra. This method was applied for the determination of a binary mixture of vildagliptin and metformin hydrochloride in the ratio 50:850 in laboratory prepared mixtures containing both drugs in this ratio and in pharmaceutical dosage form with good recoveries. The developed method was validated according to ICH guidelines and can be used for routine quality control testing.

  12. Short-peptide-based molecular hydrogels: novel gelation strategies and applications for tissue engineering and drug delivery

    Science.gov (United States)

    Wang, Huaimin; Yang, Zhimou

    2012-08-01

    Molecular hydrogels hold big potential for tissue engineering and controlled drug delivery. Our lab focuses on short-peptide-based molecular hydrogels formed by biocompatible methods and their applications in tissue engineering (especially, 3D cell culture) and controlled drug delivery. This feature article firstly describes our recent progresses of the development of novel methods to form hydrogels, including the strategy of disulfide bond reduction and assistance with specific protein-peptide interactions. We then introduce the applications of our hydrogels in fields of controlled stem cell differentiation, cell culture, surface modifications of polyester materials by molecular self-assembly, and anti-degradation of recombinant complex proteins. A novel molecular hydrogel system of hydrophobic compounds that are only formed by hydrolysis processes was also included in this article. The hydrogels of hydrophobic compounds, especially those of hydrophobic therapeutic agents, may be developed into a carrier-free delivery system for long term delivery of therapeutic agents. With the efforts in this field, we believe that molecular hydrogels formed by short peptides and hydrophobic therapeutic agents can be practically applied for 3D cell culture and long term drug delivery in near future, respectively.

  13. Effects of drugs in subtoxic concentrations on the metabolic fluxes in human hepatoma cell line Hep G2

    International Nuclear Information System (INIS)

    Niklas, Jens; Noor, Fozia; Heinzle, Elmar

    2009-01-01

    Commonly used cytotoxicity assays assess the toxicity of a compound by measuring certain parameters which directly or indirectly correlate to the viability of the cells. However, the effects of a given compound at concentrations considerably below EC 50 values are usually not evaluated. These subtoxic effects are difficult to identify but may eventually cause severe and costly long term problems such as idiosyncratic hepatotoxicity. We determined the toxicity of three hepatotoxic compounds, namely amiodarone, diclofenac and tacrine on the human hepatoma cell line Hep G2 using an online kinetic respiration assay and analysed the effects of subtoxic concentrations of these drugs on the cellular metabolism by using metabolic flux analysis. Several changes in the metabolism could be detected upon exposure to subtoxic concentrations of the test compounds. Upon exposure to diclofenac and tacrine an increase in the TCA-cycle activity was observed which could be a signature of an uncoupling of the oxidative phosphorylation. The results indicate that metabolic flux analysis could serve as an invaluable novel tool for the investigation of the effects of drugs. The described methodology enables tracking the toxicity of compounds dynamically using the respiration assay in a range of concentrations and the metabolic flux analysis permits interesting insights into the changes in the central metabolism of the cell upon exposure to drugs.

  14. Effect of Na2SO3 concentration to drug loading and drug release of ascorbic acid in chitosan edible film as drug delivery system membrane

    Directory of Open Access Journals (Sweden)

    Kistriyani Lilis

    2018-01-01

    Full Text Available Chitosan is a type of carbohydrate compounds produced from waste marine products, in particular the class of shrimp, crabs and clams. Chitosan is often process into edible films and utilized for food packaging also has potential as a membrane for drug delivery system. Drug loading and drug release can be controlled by improve the characteristics of the membrane by adding crosslinker. The purpose of this research is to study the effect of addition of crosslinker to the rate of loading and release of ascorbic acid in the chitosan edible film. Na2SO3 was used as crosslinker. Two grams of chitosan was dissolved into 100 ml of distilled water. Acetic acid and plasticizer were added in the solution then heated at 50°C. Na2SO3 solution with mass various of Na2SO3 dissolved, 01026 0.3; and 0.5 grams were added about 30 mL to make edible film. The analysis include of drug loading, drug release and tensile strength. The result showed that the loading of edible film with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 60.98 ppm; 52.53 ppm; and 40.88 ppm, meanwhile for the release with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 3.78 ppm; 5.72 ppm; and 5.97 ppm.

  15. Localized increase of tissue oxygen tension by magnetic targeted drug delivery

    Science.gov (United States)

    Liong, Celine; Ortiz, Daniel; Ao-ieong, Eilleen; Navati, Mahantesh S.; Friedman, Joel M.; Cabrales, Pedro

    2014-07-01

    Hypoxia is the major hindrance to successful radiation therapy of tumors. Attempts to increase the oxygen (O2) tension (PO2) of tissue by delivering more O2 have been clinically disappointing, largely due to the way O2 is transported and released by the hemoglobin (Hb) within the red blood cells (RBCs). Systemic manipulation of O2 transport increases vascular resistance due to metabolic autoregulation of blood flow to prevent over oxygenation. This study investigates a new technology to increase O2 delivery to a target tissue by decreasing the Hb-O2 affinity of the blood circulating within the targeted tissue. As the Hb-O2 affinity decreases, the tissue PO2 to satisfy tissue O2 metabolic needs increases without increasing O2 delivery or extraction. Paramagnetic nanoparticles (PMNPs), synthetized using gadolinium oxide, were coated with the cell permeable Hb allosteric effector L35 (3,5-trichlorophenylureido-phenoxy-methylpropionic acid). L35 decreases Hb affinity for O2 and favors the release of O2. The L35-coated PMNPs (L35-PMNPs) were intravenously infused (10 mg kg-1) to hamsters instrumented with the dorsal window chamber model. A magnetic field of 3 mT was applied to localize the effects of the L35-PMNPs to the window chamber. Systemic O2 transport characteristics and microvascular tissue oxygenation were measured after administration of L35-PMNPs with and without magnetic field. The tissue PO2 in untreated control animals was 25.2 mmHg. L35-PMNPs without magnetic field decreased tissue PO2 to 23.4 mmHg, increased blood pressure, and reduced blood flow, largely due to systemic modification of Hb-O2 affinity. L35-PMNPs with magnetic field increased tissue PO2 to 27.9 mmHg, without systemic or microhemodynamic changes. These results indicate that localized modification of Hb-O2 affinity can increase PO2 of target tissue without affecting systemic O2 delivery or triggering O2 autoregulation mechanisms. This technology can be used to treat local hypoxia and to

  16. Effects of dietary selenium on tissue concentrations,pathology, oxidative stress, and immune function in common eiders (Somateria mollissima)

    Science.gov (United States)

    Franson, J. Christian; Hoffman, David; Wells-Berlin, Alicia M.; Perry, Matthew C.; Shearn-Bochsler, Valerie I.; Finley, Daniel L.; Flint, Paul L.; Hollmén, Tuula E.

    2007-01-01

    Common eiders (Somateria mollissima) were fed added Se (as L-selenomethionine) in concentrations increasing from 10 to 80 ppm in a pilot study (Study 1) or 20 (low exposure) and up to 60 (high exposure) ppm Se in Study 2. Body weights of Study 1 ducks and high-exposure ducks in Study 2 declined rapidly. Mean concentrations of Se in blood reached 32.4 ppm wet weight in Study 1 and 17.5 ppm wet weight in high-exposure birds in Study 2. Mean Se concentrations in liver ranged from 351 (low exposure, Study 2) to 1252 ppm dry weight (Study 1). Oxidative stress was evidenced by Se-associated effects on glutathione metabolism. As Se concentrations in liver increased, Se-dependent glutathione peroxidase activity, glutathione reductase activity, oxidized glutathione levels, and the ratio of hepatic oxidized to reduced glutathione increased. In Study 2, the T-cell-mediated immune response was adversely affected in high-exposure eiders, but ducks in the low-exposure group exhibited evidence of an enhanced antibody-mediated immune response. Gross lesions in high-exposure ducks included emaciation, absence of thymus, and loss of nails from digits. Histologic lesions included severe depletion of lymphoid organs, hepatopathy, and necrosis of feather pulp and feather epithelium. Field studies showed that apparently healthy sea ducks generally have higher levels of Se in liver than healthy fresh-water birds, but lower than concentrations found in our study. Data indicate that common eiders and probably other sea ducks possess a higher threshold, or adverse effect level, for Se in tissues than fresh-water species. However, common eiders developed signs of Se toxicity similar to those seen in fresh-water birds.

  17. Concentration of rat brown adipose tissue uncoupling protein may not be correlated with 3H-GDP binding

    International Nuclear Information System (INIS)

    Henningfield, M.F.; Swick, A.G.; Swick, R.W.

    1986-01-01

    Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial 3 H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 27 0 C although 3 H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although 3 H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria

  18. An example of the application of Mössbauer spectroscopy for determination of concentration of iron in lyophilized brain tissue

    Directory of Open Access Journals (Sweden)

    Rzepecka Patrycja

    2017-06-01

    Full Text Available Mössbauer spectroscopy is not routinely used for the determination of the concentration of iron. However, as this method does not need any pre-treatment of samples before measurements, it may be of extreme importance for the assessment of iron in samples, which can then be used for further investigations. Biological samples are a good example, however, as the concentrations of iron are very low in these, it is important to exclude possible artefacts from the background spectrum related to iron present in the counter and cryostat windows. The aim of this study was to compare two methods of determination of the amounts of iron in investigated sample: one, in which the background spectrum was subtracted from the sample spectrum measured, and the other, in which the obtained non-elaborated spectrum was fitted with two doublets - a doublet for the measured sample and a doublet for the background spectrum. Three samples containing known amounts of natural iron (400, 800 and 1600 μg and a sample of lyophilized human brain tissue obtained from globus pallidus were assessed. Both methods led to the creation of a very good calibration curve with a correlation coefficient of 0.99. Although both methods gave similar results for the concentration of iron in the sample, the subtraction of the background spectrum had a significantly lower error of the final result.

  19. A near infrared instrument to monitor relative hemoglobin concentrations of human bone tissue in vitro and in vivo

    Science.gov (United States)

    Aziz, Syed Mahfuzul; Khambatta, Faram; Vaithianathan, Tharshan; Thomas, John C.; Clark, Jillian M.; Marshall, Ruth

    2010-04-01

    A continuous wave near infrared instrument has been developed to monitor in vivo changes in the hemoglobin concentration of the trabecular compartment of human bone. The transmitter uses only two laser diodes of wavelengths 685 and 830 nm, and the receiver uses a single silicon photodiode operating in the photovoltaic mode. The functioning of the instrument and the depth of penetration of the near infrared signals was determined in vitro using tissue-equivalent phantoms. The instrument achieves a depth of penetration of approximately 2 cm for an optode separation of 4 cm and, therefore, has the capacity to interrogate the trabecular compartment of human bone. The functioning of the instrument was tested in vivo to evaluate the relative oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) concentrations of the proximal tibial bone of apparently healthy, normal weight, adult subjects in response to a 3 min on, 5 min off, vascular occlusion protocol. The traces of the relative Hb and HbO2 concentrations obtained were reproducible in controlled conditions. The instrument is relatively simple and flexible, and offers an inexpensive platform for further studies to obtain normative data for healthy cohorts, and to evaluate disease-specific performance characteristics for cohorts with vasculopathies of bone.

  20. MR image enhancement as a function of tissue gadolinium concentration, measured with polarized X-ray fluorescence analysis

    International Nuclear Information System (INIS)

    Wang, S.C.; Morita, Y.; White, D.L.; Kaufman, L.; Brasch, R.C.

    1988-01-01

    MR imaging contrast agents alter intensities nonlinearly relative to their tissue concentrations. To extract Gd concentrations from image intensity data, a 13-tube phantom (Gd-DTPA dilutions, 0-10/sup -2/M) was imaged (2 T, 3 mm, spin echo, 300 = msec repetition time, 15 = msec echo time, 128 X 256, four excitations). Also, 18 rats were studied with Gd-DTPA or albumin-(Gd-DTPA)/sub 19/ (nine each, three doses). Liver and renal cortex were imaged before and 10 minutes after contrast material administration, with immediate killing and harvesting, and enhancement was calculated. These samples were assayed by x-ray fluorescent excitation analysis (150-kVp beam, B/sub 4/C ceramic polarizer, Mo-Cu-Ni filter, Si[Li] detector). Gd levels as low as 0.5 ppm (--3.18 x 10/sup -6/M) could be detected in liquid or solid samples. Enhancement increased with a nonlinear relationship to Gd in the range measured. This assay for Gd permits empiric assessment of the relationship between pulse variables, intensity, and paramagnet concentration, allowing Gd values to be estimated from image intensities

  1. Study of Fe, Zn, Cu, Cd, Pb concentrations in liver, kidney and muscle tissue of cow and sheep marketed in Hamedan in 2011

    Directory of Open Access Journals (Sweden)

    S Sobhanardakani

    2012-11-01

    Full Text Available Importance of heavy metals in food safety and detrimental effects of their high concentrations in food stuff is well documented. In this study, concentrations of Fe, Zn, Cu, Cd and Pb in kidney, liver and muscle tissues of cow and sheep at Hamedan retails were evaluated. A total number of 180 samples was assessed for the amount of heavy metals as ppb in wet weight. For this, wet-digestion method was used to determine the concentration of given elements by ICP (Varian ES-710. Results showed that the highest concentration of heavy metals was determined in the liver and kidney samples, while the lowest concentration was found in muscle tissue. Among the heavy metals, Fe in cow’s liver had the highest concentration (25507±879 ppb and Cd in muscle tissue of sheep has the lowest concentration (192±54 ppb. In overall, accumulation of heavy metals in tissues of cows was higher than sheep. Statistical comparison of accumulated metals concentration in various tissues of these two animal groups showed significant difference (P

  2. Engineering dextran-based scaffolds for drug delivery and tissue repair

    Science.gov (United States)

    Sun, Guoming; Mao, Jeremy J

    2015-01-01

    Owing to its chemically reactive hydroxyl groups, dextran can be modified with different functional groups to form spherical, tubular and 3D network structures. The development of novel functional scaffolds for efficient controlled release and tissue regeneration has been a major research interest, and offers promising therapeutics for many diseases. Dextran-based scaffolds are naturally biodegradable and can serve as bioactive carriers for many protein biomolecules. The reconstruction of the in vitro microenvironment with proper signaling cues for large-scale tissue regenerative scaffolds has yet to be fully developed, and remains a significant challenge in regenerative medicine. This paper will describe recent advances in dextran-based polymers and scaffolds for controlled release and tissue engineering. Special attention is given to the development of dextran-based hydrogels that are precisely manipulated with desired structural properties and encapsulated with defined angiogenic growth factors for therapeutic neovascularization, as well as their potential for wound repair. PMID:23210716

  3. 3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A.

    2016-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

  4. Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96 h) exposure to cadmium

    International Nuclear Information System (INIS)

    Moncaleano-Niño, Angela M.; Barrios-Latorre, Sergio A.; Poloche-Hernández, Javier F.; Becquet, Vanessa; Huet, Valérie; Villamil, Luisa; Thomas-Guyon, Hélène; Ahrens, Michael J.; Luna-Acosta, Andrea

    2017-01-01

    Highlights: • The cup oyster Saccostrea sp. is present in Santa Marta, Colombian Caribbean. • 96 h exposure of oysters to Cd increased metallothionein concentrations in digestive glands up to 2-fold. • 96 h exposure of oysters to Cd decreased vitellogenin concentrations in gonads up to 6-fold. • Metallothionein and vitellogenin tissue concentrations correlated with whole tissue Cd concentrations. • Significant changes in metallothionein and vitellogenin levels were only evident at Cd concentrations above 100 μg/L. - Abstract: Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96 h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5–5.0 cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5 days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000 μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations ≥ 100 μg/L showed a significant increase, from 8.0 to 14.8 μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297 μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96 h of exposure to 1000 μg/L Cd, were significantly lower (0

  5. Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96 h) exposure to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Moncaleano-Niño, Angela M.; Barrios-Latorre, Sergio A.; Poloche-Hernández, Javier F. [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Becquet, Vanessa; Huet, Valérie [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Villamil, Luisa [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Thomas-Guyon, Hélène [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Ahrens, Michael J., E-mail: michael.ahrens@utadeo.edu.co [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Luna-Acosta, Andrea [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia)

    2017-04-15

    Highlights: • The cup oyster Saccostrea sp. is present in Santa Marta, Colombian Caribbean. • 96 h exposure of oysters to Cd increased metallothionein concentrations in digestive glands up to 2-fold. • 96 h exposure of oysters to Cd decreased vitellogenin concentrations in gonads up to 6-fold. • Metallothionein and vitellogenin tissue concentrations correlated with whole tissue Cd concentrations. • Significant changes in metallothionein and vitellogenin levels were only evident at Cd concentrations above 100 μg/L. - Abstract: Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96 h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5–5.0 cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5 days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000 μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations ≥ 100 μg/L showed a significant increase, from 8.0 to 14.8 μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297 μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96 h of exposure to 1000 μg/L Cd, were significantly lower (0

  6. LC-MSdetermination of L-DOPA concentration in the leaf and flower tissues of six faba bean (Vicia fabaL. lines with common and rare flowercolors

    Directory of Open Access Journals (Sweden)

    Jinguo Hu

    2015-07-01

    Full Text Available Background: Parkinson’s disease (PD is the second most common neurodegenerative disorder characterized by the loss of muscle control, which causes trembling of the limbs and head as well as impaired balance. L-DOPA (L-3,4-dihydroxy phenylalanine is the major ingredient of several prescription drugs used to treat PD. Faba bean (Vicia faba L. is one of the few plant species that is known to produce L-DOPA and has the potential to be developed as a functional food crop for people suffering with PD. Objective: Aimed to provide needed information for people who want to use faba bean as a natural remedy or functional food to relieve PD symptoms, this study analyzed the variation of L-DOPA concentration in the leaf and flower tissues of six faba bean lines with common and rare flower colors. Methods: Leaf and flower samples were taken from field grown plants with different flower colors, namely, pink with purple lines and black dots, pure white, brown, and crimson. Samples were freeze-dried and L-DOPA was quantified by a LC-MS system consisting of an ACQUITY UPLC in line with a Synapt G2 HDMS quadrupole time-of-flight mass spectrometer. This experiment was carried out in two consecutive years (2012 and 2013 and the plants used in the second year were grown from the seeds harvested from the plants used in the first year. Results and Discussion: Our two-year study revealed a high level of variation in L-DOPA concentration for leaf and flower tissues among the six faba bean lines studied. The average L-DOPA concentration based on dry weight (DW in flowers ranged from 27.8 to 63.5 mg/g and 18.2 to 48.7 mg/g for leaf tissues. There was no significant correlation between L-DOPA concentrations in flowers and leaves. The L-DOPA concentration in flowers and in leaves of the same line varied but were not statistically significant between the two years. Ideally, the genotype with the highest average L-DOPA concentration in both flowers and leaves would be grown

  7. Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-02-01

    The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

  8. Green Tea Increases the Concentration of Total Mercury in the Blood of Rats following an Oral Fish Tissue Bolus

    Directory of Open Access Journals (Sweden)

    Elsa M. Janle

    2015-01-01

    Full Text Available Fish has many health benefits but is also the most common source of methylmercury. The bioavailability of methylmercury in fish may be affected by other meal components. In this study, the effect of green tea on the bioavailability of methylmercury from an oral bolus of fish muscle tissue was studied in rats and compared to a water treated control group and a group treated with meso-2,3-dimercaptosuccinic acid (DMSA, a compound used medically to chelate mercury. Rats were given a single oral dose of fish tissue via gavage and one of the treatments. Rats were given access to food for 3 h at 12 h intervals. They were dosed with each of the treatments with each meal. Blood samples were collected for 95 hours. Green tea significantly increased the concentration of total mercury in blood relative to the control, whereas DMSA significantly decreased it. In addition, feeding caused a slight increase in blood mercury for several meals following the initial dose.

  9. Illicit drug detection with laser 1: investigation of optimal parameters in stomach tissue

    Science.gov (United States)

    Özer, Ayşen Gürkan; Tabakoğlu, Haşim Özgür; Cengiz, Salih

    2014-05-01

    The main purpose of this study is to establish radiation-safe scanning of passersby at high security areas, such as airports and customs. The stomach was selected as the organ to be analyzed. In order to determine whether a substance found inside a human body as wrapped in a plastic bag is filled narcotics or not, many substances in white powder form including morphine-HCL were inspected. Inspection was carried out with on-ionizing radiation by irradiating stomach tissue with laser light. Optical transmittance of lamb stomach tissue was analyzed at different wavelengths. We showed that detection by 650-nm diode laser irradiation would be suitable for such a radiation-safe scan. Different materials were also investigated for absorptive properties, and closed system Raman studies were performed. The spectrum of a molecule found inside white powder placed behind the lamb stomach tissue was detected as a fingerprint. This allowed the detection of target substances without any physical contact or damage to the biological tissue.

  10. Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations

    International Nuclear Information System (INIS)

    Meador, James P.; Yeh, Andrew; Gallagher, Evan P.

    2017-01-01

    The Fish Plasma Model (FPM) was applied to water exposure and tissue concentrations in fish collected from two wastewater treatment plant impacted estuarine sites. In this study we compared predicted fish plasma concentrations to Cmax values for humans, which represents the maximum plasma concentration for the minimum therapeutic dose. The results of this study show that predictions of plasma concentrations for a variety of pharmaceutical and personal care products (PPCPs) from effluent concentrations resulted in 37 compounds (54%) exceeding the response ratio (RR = Fish [Plasma]/1%Cmax total ) of 1 compared to 3 compounds (14%) detected with values generated with estuarine receiving water concentrations. When plasma concentrations were modeled from observed whole-body tissue residues, 16 compounds out of 24 detected for Chinook (67%) and 7 of 14 (50%) for sculpin resulted in an RR tissue value greater than 1, which highlights the importance of this dose metric over that using estuarine water. Because the tissue residue approach resulted in a high percentage of compounds with calculated response ratios exceeding a value of unity, we believe this is a more accurate representation for exposure in the field. Predicting plasma concentrations from tissue residues improves our ability to assess the potential for adverse effects in fish because exposure from all sources is captured. Tissue residues are also more likely to represent steady-state conditions compared to those from water exposure because of the inherent reduction in variability usually observed for field data and the time course for bioaccumulation. We also examined the RR in a toxic unit approach to highlight the importance of considering multiple compounds exhibiting a similar mechanism of action. - Highlights: • Fish Plasma Model (FPM) to assess risk based on water and fish tissue concentrations. • Plasma levels predicted with receiving water concentrations underestimate exposure for feral fish.

  11. Mass Spectrometry to Determine Intracellular Concentrations of Antiretroviral Drugs: From chemistry to clinical application

    NARCIS (Netherlands)

    J.J.A. van Kampen (Jeroen)

    2009-01-01

    textabstractAround 1995 – 1996, treatment options for patients infected with the human immunodefiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) 1, 2, improved dramatically. Therapy with a combination of several classes of antiretroviral drugs resulted in a

  12. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans.

    Science.gov (United States)

    Glaeser, Hartmut; Drescher, Siegfried; Hofmann, Ute; Heinkele, Georg; Somogyi, Andrew A; Eichelbaum, Michel; Fromm, Martin F

    2004-09-01

    In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (F(abs)) and gastrointestinal extraction (E(GI)) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil 15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil 240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for F abs ) (F/F abs d3-verapamil 240 min versus d0-verapamil 15 min, 0.24 +/- 0.10 versus 0.20 +/- 0.09; P d3-verapamil 240 min was 0.50 +/- 0.18 compared with 0.59 +/- 0.14 for d0 -verapamil 15 min ( P d0-verapamil 15 min ) correlated strongly with E GI (d3-verapamil 240 min ) (r = 0.94, P d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.

  13. Effect of certain variables on the tumor and tissue distribution of tracers. Salicylates and vasoactive drugs

    International Nuclear Information System (INIS)

    Halpern, S.E.; Hagan, P.; Stern, P.; Gordon, R.; Dabbs, J.

    1981-01-01

    Attempts were made to increase the viable tumor concentration of 54Mn and 67Ga in a rat hepatoma model by administering rat angiotensin, tolazoline, and salicylates. Salicylates increased the tumor concentrations of 54Mn and improved 65Mn viable tumor/background ratios. 67Ga was not affected by the salicylates. The salicylate effect appeared to be mediated by intracellular mechanisms rather than alterations in plasma protein binding. Rat angiotensin slightly increased the concentrations of 67Ga in the tumors but not enough to suggest that it would be useful clinically. Tolazoline did not increase tumor uptake of the tracers

  14. Relations of Visceral and Abdominal Subcutaneous Adipose Tissue, Body Mass Index, and Waist Circumference to Serum Concentrations of Parameters of Chronic Inflammation

    Directory of Open Access Journals (Sweden)

    Inga Schlecht

    2016-06-01

    Full Text Available Background: Different measures of body fat composition may vary in their relations to parameters of chronic inflammation. Methods: We assessed the relations of visceral (VAT and subcutaneous adipose tissue (SAT, BMI, and waist circumference (WC to serum concentrations of high-sensitive C-reactive protein (hs-CRP, tumor necrosis factor alpha (TNF-α, interleukin-6 (IL-6, resistin, and adiponectin in 97 healthy adults using multivariate linear regression models, adjusted for age, sex, smoking, physical activity, menopausal status, and use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs. Parameters of chronic inflammation were mutually adjusted. Results: VAT (β = 0.34, SAT (β = 0.43, BMI (β = 0.40, and WC (β = 0.47 were all significantly associated with hs-CRP. BMI was additionally inversely related to adiponectin (β = -0.29. In exploratory subgroup analyses defined by gender, BMI, smoking, and use of aspirin or NSAIDs, VAT was the strongest indicator for increased levels of IL-6, SAT was the most consistent indicator for increased levels of hs-CRP, and BMI was the most consistent indicator for decreased levels of adiponectin. WC showed to be a weak indicator for increased levels of hs-CRP and decreased levels of adiponectin. Conclusion: VAT, SAT, BMI, and WC show distinct associations with parameters of chronic inflammation. Whether these differences reflect differential metabolic risks requires clarification by longitudinal studies.

  15. Lethal concentrations of heavy metals in tissue of earthworms. Interim report No. 1, June-July 1987

    Energy Technology Data Exchange (ETDEWEB)

    Bouche, M.B.; Brun, P.; Gal, J.Y.; Reza, A.

    1987-07-01

    The objective of this phase of Toxicological Research on Lethal Concentrations of Heavy Metals in Tissue of Earthworms is to improve both ecotoxicological tests in a chemically defined medium and a procedure of bioavailability study in field. In this first period the authors worked on breeding stock of earthworms (species Eisenia fetida andrei) in decomposing manure heaps to increase them and make them grow. They also installed two chambers with thermostats fixed at 20 C to do toxicity tests and chose chemical species of heavy-metal contaminants. For field procedure, they improved a practical way to sample both earthworms and soil in very close connections, avoiding artifacts. For both field procedure and laboratory tests, they tried to standardize a method to dissolve earthworms in acids and to analyze the concentrations of heavy metals inside. A preliminary set of samples in calcareous soils was started and analysis of them are in progress. For lab tests, the first part of the test (preliminary test) was started with the different contaminants (cadmium, copper, arsenic, mercury) in an artificial medium named Artisol.

  16. Adipose tissue concentrations of PCB, HCB, chlordane, PBDE and P,P'-DDE and the risk for endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lindstroem, G.; Bavel, B. van; Bjoernfoth, H. [MTM Research Centre, Oerebro Univ., Oerebro (Sweden); Hardell, L. [Dept. of Oncology, Univ. Hospital, Oerebro (Sweden)

    2004-09-15

    adipose tissue concentrations of certain POPs, parity and hormone replacement as potential risk factors in women in relation to development of endometrial cancer.

  17. Murine strain differences and the effects of zinc on cadmium concentrations in tissues after acute cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    King, L.M. [ARS USDA, Germplasm and Gamete Physiology Lab., Beltsville, MD (United States); Anderson, M.B. [Dept. of Anatomy, Tulane Univ. School of Medicine, New Orleans, LA (United States); Sikka, S.C. [Dept. of Urology, Tulane Univ. School of Medicine, New Orleans, LA (United States); George, W.J. [Dept. of Pharmacology, Tulane Univ. School of Medicine, New Orleans, LA (United States)

    1998-10-01

    The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 {mu}mol/kg CdCl{sub 2}). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 {mu}mol/kg ZnAc), given 24 h prior to 20 {mu}mol/kg CdCl{sub 2} administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible

  18. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

    Directory of Open Access Journals (Sweden)

    Laine J

    2016-04-01

    Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

  19. Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations.

    Science.gov (United States)

    Meador, James P; Yeh, Andrew; Gallagher, Evan P

    2017-11-01

    The Fish Plasma Model (FPM) was applied to water exposure and tissue concentrations in fish collected from two wastewater treatment plant impacted estuarine sites. In this study we compared predicted fish plasma concentrations to Cmax values for humans, which represents the maximum plasma concentration for the minimum therapeutic dose. The results of this study show that predictions of plasma concentrations for a variety of pharmaceutical and personal care products (PPCPs) from effluent concentrations resulted in 37 compounds (54%) exceeding the response ratio (RR = Fish [Plasma]/1%Cmax total ) of 1 compared to 3 compounds (14%) detected with values generated with estuarine receiving water concentrations. When plasma concentrations were modeled from observed whole-body tissue residues, 16 compounds out of 24 detected for Chinook (67%) and 7 of 14 (50%) for sculpin resulted in an RR tissue value greater than 1, which highlights the importance of this dose metric over that using estuarine water. Because the tissue residue approach resulted in a high percentage of compounds with calculated response ratios exceeding a value of unity, we believe this is a more accurate representation for exposure in the field. Predicting plasma concentrations from tissue residues improves our ability to assess the potential for adverse effects in fish because exposure from all sources is captured. Tissue residues are also more likely to represent steady-state conditions compared to those from water exposure because of the inherent reduction in variability usually observed for field data and the time course for bioaccumulation. We also examined the RR in a toxic unit approach to highlight the importance of considering multiple compounds exhibiting a similar mechanism of action. Published by Elsevier Ltd.

  20. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

    2013-07-15

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K{sub M} 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V{sub max}. PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion

  1. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    International Nuclear Information System (INIS)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François

    2013-01-01

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K M 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V max . PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion trapping

  2. 3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lagerloef, Jakob H.; Kindblom, Jon; Bernhardt, Peter [Department of Radiation Physics, Goeteborg University, Goeteborg 41345 (Sweden); Department of Oncology, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden); Department of Radiation Physics, Goeteborg University, Goeteborg, Sweden and Department of Nuclear Medicine, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden)

    2011-08-15

    Purpose: Formation of new blood vessels (angiogenesis) in response to hypoxia is a fundamental event in the process of tumor growth and metastatic dissemination. However, abnormalities in tumor neovasculature often induce increased interstitial pressure (IP) and further reduce oxygenation (pO{sub 2}) of tumor cells. In radiotherapy, well-oxygenated tumors favor treatment. Antiangiogenic drugs may lower IP in the tumor, improving perfusion, pO{sub 2} and drug uptake, by reducing the number of malfunctioning vessels in the tissue. This study aims to create a model for quantifying the effects of altered pO{sub 2}-distribution due to antiangiogenic treatment in combination with radionuclide therapy. Methods: Based on experimental data, describing the effects of antiangiogenic agents on oxygenation of GlioblastomaMultiforme (GBM), a single cell based 3D model, including 10{sup 10} tumor cells, was developed, showing how radionuclide therapy response improves as tumor oxygenation approaches normal tissue levels. The nuclides studied were {sup 90}Y, {sup 131}I, {sup 177}Lu, and {sup 211}At. The absorbed dose levels required for a tumor control probability (TCP) of 0.990 are compared for three different log-normal pO{sub 2}-distributions: {mu}{sub 1} = 2.483, {sigma}{sub 1} = 0.711; {mu}{sub 2} = 2.946, {sigma}{sub 2} = 0.689; {mu}{sub 3} = 3.689, and {sigma}{sub 3} = 0.330. The normal tissue absorbed doses will, in turn, depend on this. These distributions were chosen to represent the expected oxygen levels in an untreated hypoxic tumor, a hypoxic tumor treated with an anti-VEGF agent, and in normal, fully-oxygenated tissue, respectively. The former two are fitted to experimental data. The geometric oxygen distributions are simulated using two different patterns: one Monte Carlo based and one radially increasing, while keeping the log-normal volumetric distributions intact. Oxygen and activity are distributed, according to the same pattern. Results: As tumor pO{sub 2

  3. Ecotoxicoparasitology: Understanding mercury concentrations in gut contents, intestinal helminths and host tissues of Alaskan gray wolves (Canis lupus)

    Science.gov (United States)

    McGrew, Ashley K.; O'Hara, Todd M.; Stricker, Craig A.; Castellini, Margaret; Beckmen, Kimberlee B.; Salman, Mo D.; Ballweber, Lora R.

    2015-01-01

    Some gastrointestinal helminths acquire nutrients from the lumen contents in which they live; thus, they may be exposed to non-essential elements, such as mercury (Hg), during feeding. The objectives of this study were: 1) determine the total mercury concentrations ([THg]) in Gray wolves (Canis lupus) and their parasites, and 2) use stable isotopes to evaluate the trophic relationships within the host. [THg] and stable isotopes (C and N) were determined for helminths, host tissues, and lumen contents from 88 wolves. Sixty-three wolves contained grossly visible helminths (71.5%). The prevalence of taeniids and ascarids was 63.6% (56/88) and 20.5% (18/88), respectively. Nine of these 63 wolves contained both taeniids and ascarids (14.3%). All ascarids were determined to beToxascaris leonina. Taenia species present included T. krabbei and T. hydatigena. Within the GI tract, [THg] in the lumen contents of the proximal small intestine were significantly lower than in the distal small intestine. There was a significant positive association between hepatic and taeniid [THg]. Bioaccumulation factors (BAF) ranged from < 1 to 22.9 in taeniids, and 1.1 to 12.3 in T. leonina. Taeniid and ascarid BAF were significantly higher than 1, suggesting that both groups are capable of THg accumulation in their wolf host. δ13C in taeniids was significantly lower than in host liver and skeletal muscle. [THg] in helminths and host tissues, in conjunction with stable isotope (C and N) values, provides insight into food-web dynamics of the host GI tract, and aids in elucidating ecotoxicoparasitologic relationships. Variation of [THg] throughout the GI tract, and between parasitic groups, underscores the need to further evaluate the effect(s) of feeding niche, and the nutritional needs of parasites, as they relate to toxicant exposure and distribution within the host.

  4. Concentration and drug prices in the retail market for malaria treatment in rural Tanzania.

    Science.gov (United States)

    Goodman, Catherine; Kachur, S Patrick; Abdulla, Salim; Bloland, Peter; Mills, Anne

    2009-06-01

    The impact of market concentration has been little studied in markets for ambulatory care in the developing world, where the retail sector often accounts for a high proportion of treatments. This study begins to address this gap through an analysis of the consumer market for malaria treatment in rural areas of three districts in Tanzania. We developed methods for investigating market definition, sales volumes and concentration, and used these to explore the relationship between antimalarial retail prices and competition.The market was strongly geographically segmented and highly concentrated in terms of antimalarial sales. Antimalarial prices were positively associated with market concentration. High antimalarial prices were likely to be an important factor in the low proportion of care-seekers obtaining appropriate treatment.Retail sector distribution of subsidised antimalarials has been proposed to increase the coverage of effective treatment, but this analysis indicates that local market power may prevent such subsidies from being passed on to rural customers. Policymakers should consider the potential to maintain lower retail prices by decreasing concentration among antimalarial providers and recommending retail price levels. Copyright (c) 2009 John Wiley & Sons, Ltd.

  5. Probe for intracellular concentrations of drugs: delayed fluorescence from acridine orange

    International Nuclear Information System (INIS)

    Wardman, P.; Dennis, M.F.; White, J.

    1989-01-01

    The aim of this work is to develop fluorescent probes that will indicate effective concentrations of therapeutic agents, or endogenous protectors, at important cellular sites. Acridine orange associates with nucleic acids and emits a 'delayed' fluorescence signal. This signal is quenched by oxidants such as oxygen, nitroaryl radiosensitizers, adriamycin and mitomycin-c, and reductants such as thiols, ascorbate and other radioprotectors. The quenching of the acridine orange delayed fluorescence reflects the effective concentration of these therapeutically-important oxidants and reductants near DNA. The relative concentration of basic radiosensitizers such as pimonidazole (Ro 03-8799) near the DNA is greater than that of misonidazole. Thiols quench the delayed fluorescence signal according to the degree of ionization of the thiol function; this may model the reactivity of thiols with guanine radical sites in DNA. Ascorbate and aminopyrine do not quench the delayed fluorescence from cells stained with acridine orange as these compounds are taken up by cells very inefficiently

  6. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  7. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin

    Science.gov (United States)

    Foster, Derek M.; Martin, Luke G.; Papich, Mark G.

    2016-01-01

    Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900

  8. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin.

    Directory of Open Access Journals (Sweden)

    Derek M Foster

    Full Text Available Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL, and the MIC90 for Mannheimia haemolytica (1.0 μg/mL for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations

  9. Experimental Determination of Drug Diffusion Coefficients in Unstirred Aqueous Environments by Temporally Resolved Concentration Measurements

    DEFF Research Database (Denmark)

    Di Cagno, Massimiliano Pio; Clarelli, Fabrizio; Vabenø, Jon

    2018-01-01

    or the need for dedicated instrumentation. In this work, a simple but reliable method based on time resolved concentration measurements by UV-visible spectroscopy in an unstirred aqueous environment was developed. This method is based on spectroscopic measurement of the variation of the local concentration...... characteristics (i.e. ionic strength and presence of complexing agents) on the diffusivity. The method can be employed in any research laboratory equipped with a standard UV-visible spectrophotometer, and could become a useful and straightforward tool in order to characterize diffusion coefficients...

  10. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    Science.gov (United States)

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

  11. Mesoporous silicate nanoparticles/3D nanofibrous scaffold-mediated dual-drug delivery for bone tissue engineering.

    Science.gov (United States)

    Yao, Qingqing; Liu, Yangxi; Selvaratnam, Balaranjan; Koodali, Ranjit T; Sun, Hongli

    2018-04-09

    Controlled delivery systems play a critical role in the success of bone morphogenetic proteins (i.e., BMP2 and BMP7) for challenged bone repair. Instead of single-drug release that is currently and commonly prevalent, dual-drug delivery strategies are highly desired to achieve effective bone regeneration because natural bone repair process is driven by multiple factors. Particularly, angiogenesis is essential for osteogenesis and requires more than just one factor (e.g., Vascular Endothelial Growth Factor, VEGF). Therefore, we developed a novel mesoporous silicate nanoparticles (MSNs) incorporated-3D nanofibrous gelatin (GF) scaffold for dual-delivery of BMP2 and deferoxamine (DFO). DFO is a hypoxia-mimetic drug that can activate hypoxia-inducible factor-1 alpha (HIF-1α), and trigger subsequent angiogenesis. Sustained BMP2 release system was achieved through encapsulation into large-pored MSNs, while the relative short-term release of DFO was engineered through covalent conjugation with chitosan to reduce its cytotoxicity and elongate its half-life. Both MSNs and DFO were incorporated onto a porous 3D GF scaffold to serve as a biomimetic osteogenic microenvironment. Our data indicated that DFO and BMP2 were released from a scaffold at different release rates (10 vs 28 days) yet maintained their angiogenic and osteogenic ability, respectively. Importantly, our data indicated that the released DFO significantly improved BMP2-induced osteogenic differentiation where the dose/duration was important for its effects in both mouse and human stem cell models. Thus, we developed a novel and tunable MSNs/GF 3D scaffold-mediated dual-drug delivery system and studied the potential application of the both FDA-approved DFO and BMP2 for bone tissue engineering. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Differential mechanism of Escherichia coli Inactivation by (+)-limonene as a function of cell physiological state and drug's concentration.

    Science.gov (United States)

    Chueca, Beatriz; Pagán, Rafael; García-Gonzalo, Diego

    2014-01-01

    (+)-limonene is a lipophilic antimicrobial compound, extracted from citrus fruits' essential oils, that is used as a flavouring agent and organic solvent by the food industry. A recent study has proposed a common and controversial mechanism of cell death for bactericidal antibiotics, in which hydroxyl radicals ultimately inactivated cells. Our objective was to determine whether the mechanism of Escherichia coli MG1655 inactivation by (+)-limonene follows that of bactericidal antibiotics. A treatment with 2,000 μL/L (+)-limonene inactivated 4 log10 cycles of exponentially growing E. coli cells in 3 hours. On one hand, an increase of cell survival in the ΔacnB mutant (deficient in a TCA cycle enzyme), or in the presence of 2,2'-dipyridyl (inhibitor of Fenton reaction by iron chelation), thiourea, or cysteamine (hydroxyl radical scavengers) was observed. Moreover, the ΔrecA mutant (deficient in an enzyme involved in SOS response to DNA damage) was more sensitive to (+)-limonene. Thus, this indirect evidence indicates that the mechanism of exponentially growing E. coli cells inactivation by 2,000 μL/L (+)-limonene is due to the TCA cycle and Fenton-mediated hydroxyl radical formation that caused oxidative DNA damage, as observed for bactericidal drugs. However, several differences have been observed between the proposed mechanism for bactericidal drugs and for (+)-limonene. In this regard, our results demonstrated that E. coli inactivation was influenced by its physiological state and the drug's concentration: experiments with stationary-phase cells or 4,000 μL/L (+)-limonene uncovered a different mechanism of cell death, likely unrelated to hydroxyl radicals. Our research has also shown that drug's concentration is an important factor influencing the mechanism of bacterial inactivation by antibiotics, such as kanamycin. These results might help in improving and spreading the use of (+)-limonene as an antimicrobial compound, and in clarifying the controversy about

  13. Determination of the exposure parameters that maximise the concentrations of the anaesthetic/sedative eugenol in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue

    Science.gov (United States)

    Meinertz, Jeffery R.; Porcher, Scott T.; Smerud, Justin R.

    2014-01-01

    Studies were conducted to determine the anaesthetic/sedative concentrations and durations that would maximize anaesthetic/sedative residue concentrations in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue. Rainbow trout (167–404 g) were exposed to 50 mg l−1 AQUI-S® 20E (10% active ingredient, eugenol) in 17°C freshwater for durations up to 1440 min, 100 and 250 mg l−1 AQUI-S® 20E for durations up to 240 min, and 500 and 1000 mg l−1 AQUI-S® 20E for durations up to 90 min. Fish exposed to 100 mg l−1 AQUI-S® 20E for durations of 30, 60, 120 and 240 min had the greatest eugenol concentrations in the fillet tissue, 50, 58, 54 and 62 µg g−1, respectively. All other exposure concentrations and durations resulted in significantly lower eugenol concentrations, i.e. all −1.

  14. Determination of the exposure parameters that maximise the concentrations of the anaesthetic/sedative eugenol in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue.

    Science.gov (United States)

    Meinertz, J R; Porcher, S T; Smerud, J R; Gaikowski, M P

    2014-01-01

    Studies were conducted to determine the anaesthetic/sedative concentrations and durations that would maximise anaesthetic/sedative residue concentrations in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue. Rainbow trout (167-404 g) were exposed to 50 mg l(-1) AQUI-S(®) 20E (10% active ingredient, eugenol) in 17°C freshwater for durations up to 1440 min, 100 and 250 mg l(-1) AQUI-S(®) 20E for durations up to 240 min, and 500 and 1000 mg l(-1) AQUI-S(®) 20E for durations up to 90 min. Fish exposed to 100 mg l(-1) AQUI-S(®) 20E for durations of 30, 60, 120 and 240 min had the greatest eugenol concentrations in the fillet tissue, 50, 58, 54 and 62 µg g(-1), respectively. All other exposure concentrations and durations resulted in significantly lower eugenol concentrations, i.e. all < 39 µg g(-1).

  15. The role of nonsteroidal anti-inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice.

    Science.gov (United States)

    Ture, Zeynep; Demiraslan, Hayati; Kontas, Olgun; Alp, Emine; Doganay, Mehmet

    2018-04-01

    The aim of this study was to determine the role of nonsteroidal anti-inflammatory drugs (NSAID) injection on the severity of local infection and the effect on the progression of soft tissue infection (STI).The mouse model of STI with Group A streptococcus (GAS) was developed and treated with diclofenac sodium (DS) intramuscularly. Mice were divided into five groups: administered DS for 48 h before GAS (Group 1), GAS-DS and maintained DS for 48 h (Group 2), DS for 48 h (Group 3), GAS on zero time (Group 4), and control (Group 5). In vitro, a high concentration (40 mg/L) of DS inhibited GAS growth, whereas a lower concentration (0.4 mg/L) was not effective. Sepsis was observed in animals with DS and GAS inoculation (group 1 and 2). Group 4 had statistically significant higher bacterial load than groups 1 and 2. All groups had a higher inflammation rate than the control group. The median of TNF-alpha and mean IL-6 in the groups 1, 2, and 4 was significantly higher than those in the control group. Even if the animals that were treated with DS injection prior to the GAS inoculation had similar inflammation score, similar cytokine levels and low bacterial load in the tissue, they had a rather high rate of sepsis. In conclusion, DS injection prior to bacterial inoculation might predispose to bacteremia and sepsis. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  16. Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

    Science.gov (United States)

    Dobard, Charles; Sharma, Sunita; Martin, Amy; Pau, Chou-Pong; Holder, Angela; Kuklenyik, Zsuzsanna; Lipscomb, Jonathan; Hanson, Debra L; Smith, James; Novembre, Francis J; García-Lerma, J Gerardo; Heneine, Walid

    2012-01-01

    A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.

  17. Distribution and persistence of emamectin benzoate at efficacious concentrations in pine tissues after injection of a liquid formulation.

    Science.gov (United States)

    Takai, Kazuya; Suzuki, Toshio; Kawazu, Kazuyoshi

    2004-01-01

    In an earlier paper the authors reported the creation of a novel emamectin benzoate 40 g litre(-1) liquid formulation (Shot Wan Liquid Formulation). The injection of this formulation exerted a preventative effect against the pine wilt disease caused by the pine wood nematode, Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle, and this effect lasted for at least 3 years. The present study was carried out to show experimentally that the marked effect of this formulation was due to the presence and persistence in pine tissues of sufficient amounts of emamectin benzoate to inhibit nematode propagation. A cleanup procedure prior to quantitative analysis of emamectin benzoate by fluorescence HPLC was devised. The presence of the compound in concentrations sufficient to inhibit nematode propagation in the shoots of current growth and its persistence for 3 years explained the marked preventative effect. Non-distribution of emamectin benzoate in some parts of the lower trunk suggested that the formulation should be injected at several points for large trees in order to distribute the compound uniformly to lower branches.

  18. Alkylation of human hair keratin for tunable hydrogel erosion and drug delivery in tissue engineering applications.

    Science.gov (United States)

    Han, Sangheon; Ham, Trevor R; Haque, Salma; Sparks, Jessica L; Saul, Justin M

    2015-09-01

    Polymeric biomaterials that provide a matrix for cell attachment and proliferation while achieving delivery of therapeutic agents are an important component of tissue engineering and regenerative medicine strategies. Keratins are a class of proteins that have received attention for numerous tissue engineering applications because, like other natural polymers, they promote favorable cell interactions and have non-toxic degradation products. Keratins can be extracted from various sources including human hair, and they are characterized by a high percentage of cysteine residues. Thiol groups on reductively extracted keratin (kerateine) form disulfide bonds, providing a more stable cross-linked hydrogel network than oxidatively extracted keratin (keratose) that cannot form disulfide crosslinks. We hypothesized that an iodoacetamide alkylation (or "capping") of cysteine thiol groups on the kerateine form of keratin could be used as a simple method to modulate the levels of disulfide crosslinking in keratin hydrogels, providing tunable rates of gel erosion and therapeutic agent release. After alkylation, the alkylated kerateines still formed hydrogels and the alkylation led to changes in the mechanical and visco-elastic properties of the materials consistent with loss of disulfide crosslinking. The alkylated kerateines did not lead to toxicity in MC3T3-E1 pre-osteoblasts. These cells adhered to keratin at levels comparable to fibronectin and greater than collagen. Alkylated kerateine gels eroded more rapidly than non-alkylated kerateine and this control over erosion led to tunable rates of delivery of rhBMP-2, rhIGF-1, and ciprofloxacin. These results demonstrate that alkylation of kerateine cysteine residues provides a cell-compatible approach to tune rates of hydrogel erosion and therapeutic agent release within the context of a naturally-derived polymeric system. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. Mercury and Methylmercury Concentrations in Muscle Tissue of Fish Caught in Major Rivers of the Czech Republic

    Directory of Open Access Journals (Sweden)

    K. Kružíková

    2008-01-01

    Full Text Available The aim of the study was to evaluate mercury contamination at twelve outlet sites of rivers in the Czech Republic (Labe, Ohře, Vltava, Berounka, Sázava, Otava, Lužnice, Svratka, Dyje, Morava and Odra. As an indicator, we used muscle tissue of the chub (Leuciscus cephalus caught at selected sites in 2007. A total of 96 fish were examined. Total mercury was determined by atomic absorption spectrophotometry using the AMA 254 analyzer and methylmercury was determined by gas chromatography with electron-capture detection. Total mercury (THg and methylmercury (MeHg concentrations ranged 0.039–0.384 mg kg-1 fresh weight and 0.033–0.362 mg kg-1 fresh weight, respectively. Mercury bound in methylmercury (HgMe made up on average about 82.2% of total mercury. The highest mercury concentrations were found in fish from Obříství, a site on Labe (THg 0.263 ± 0.086 mg kg-1; MeHg 0.256 ± 0.084 mg kg-1. Mercury concentrations in fish from rivers that cross the borders of the Czech Republic (Labe, Odra and Morava were low. The Czech Republic therefore does not contribute significantly to river pollution outside its national borders. Hazard indices of the sites monitored were well below 1, and reached 1.365 only in Obříství on Labe for fisherman’s family members (i.e. in the case of annual consumption of 10 kg fish. This indicates possible hazards involved in eating meat of fish caught in that location. Based on PTWI for methylmercury, the maximum amount of fish meat allowed for consumption per week was calculated. The site with the lowest value was Obříství on Labe (0.44 kg. The results of this study present a partial contribution to health risk assessment on the major rivers in Czech Republic.

  20. Relationship between biomarker responses and contaminant concentration in selected tissues of flounder (Platichthys flesus from the Polish coastal area of the Baltic Sea

    Directory of Open Access Journals (Sweden)

    Magdalena Podolska

    2008-09-01

    Full Text Available Previous studies in the Gulf of Gdańsk discussed the responses of selected enzymatic biomarkers to the contaminant gradient in fish and mussels. In the present study, flounder muscle and liver tissues were analyzed for polychlorinated biphenyls (PCB congeners: 28, 52, 101, 118, 138, 153 and 180, organochlorine pesticides (HCHs, HCB and DDTs, and trace metals (Pb, Cd, Zn, Cu, Hg, Cr. An attempt was made to identify the relationship between the measured enzymatic biomarker responses (cholinesterases, malic enzyme, isocitrate dehydrogenase, glutathione S-transferase and contaminant concentrations in selected flounder tissues. The observed differences in enzymatic biomarker levels suggest that chronic exposure to low-concentration mixtures of contaminants may be occurring in the studied area. However, no conclusive evidence was found of a clear link between the biomarker responses and contaminant concentrations in flounder tissues.

  1. Concentrations and distributions of metals in tissues of stranded green sea turtles (Chelonia mydas) from the southern Atlantic coast of Brazil

    International Nuclear Information System (INIS)

    da Silva, Cinthia Carneiro; Varela, Antonio Sergio; Barcarolli, Indianara Fernanda; Bianchini, Adalto

    2014-01-01

    Silver (Ag), cadmium (Cd), copper (Cu), lead (Pb) and zinc (Zn) concentrations were analyzed in tissues of juvenile green sea turtles (Chelonia mydas) found stranded along the southern Atlantic coast in Brazil. Green sea turtles were collected (n = 29), measured (curved carapace length: CCL) and had their muscle, liver, and kidney dissected for metal concentration measurements. Sex was identified in 18 individuals (10 females and 8 males) through gonad histology. No gender differences in CCL and tissue metal concentrations were observed. In the muscle, there was a negative correlation between CCL and Cd and Cu concentrations. Metal concentrations were lower in the muscle than in the liver and kidney. Zn concentration in the muscle was the highest of all metals analyzed (16.6 mg/kg). The kidney showed the highest concentrations of Pb, Cd and Zn (5.4, 28.3 and 54.3 mg/kg, respectively), while the liver had the highest values of Ag and Cu (0.8 and 100.9 mg/kg, respectively). Tissue Ag, Zn and Cd concentrations were similar to those found in green sea turtles from other regions while Cu and Pb values were elevated, likely due to the metal-rich water and sediment reported in the collection area. In the liver and kidney, concentrations of non-essential (Ag, Cd and Pb) and essential (Cu or Zn) metals were positively correlated, likely due to an induced metallothionein synthesis to protect tissue against the toxic effect of metals. This is the first study to report and correlate the concentrations of essential and non-essential metals in tissues of green sea turtles in the Brazilian southern Atlantic coast, an important feeding and developing area for this turtle species. - Highlights: •Juvenile female and male green sea turtles have similar concentrations of metals. •Kidney accumulated more Cd, Pb and Zn while liver accumulated more Ag and Cu. •Cu and Pb concentrations are elevated in liver of sea turtles from southern Brazil. •Concentrations of Cd and Cu in

  2. Concentrations and distributions of metals in tissues of stranded green sea turtles (Chelonia mydas) from the southern Atlantic coast of Brazil

    Energy Technology Data Exchange (ETDEWEB)

    da Silva, Cinthia Carneiro [Programa de Pós-Graduação em Ciências Fisiológicas – Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Av. Itália km 8, 96203-900, Rio Grande, Rio Grande do Sul (Brazil); Varela, Antonio Sergio; Barcarolli, Indianara Fernanda [Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Av. Itália km 8, 96203-900, Rio Grande, Rio Grande do Sul (Brazil); Bianchini, Adalto, E-mail: adaltobianchini@furg.br [Programa de Pós-Graduação em Ciências Fisiológicas – Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Av. Itália km 8, 96203-900, Rio Grande, Rio Grande do Sul (Brazil); Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Av. Itália km 8, 96203-900, Rio Grande, Rio Grande do Sul (Brazil)

    2014-01-01

    Silver (Ag), cadmium (Cd), copper (Cu), lead (Pb) and zinc (Zn) concentrations were analyzed in tissues of juvenile green sea turtles (Chelonia mydas) found stranded along the southern Atlantic coast in Brazil. Green sea turtles were collected (n = 29), measured (curved carapace length: CCL) and had their muscle, liver, and kidney dissected for metal concentration measurements. Sex was identified in 18 individuals (10 females and 8 males) through gonad histology. No gender differences in CCL and tissue metal concentrations were observed. In the muscle, there was a negative correlation between CCL and Cd and Cu concentrations. Metal concentrations were lower in the muscle than in the liver and kidney. Zn concentration in the muscle was the highest of all metals analyzed (16.6 mg/kg). The kidney showed the highest concentrations of Pb, Cd and Zn (5.4, 28.3 and 54.3 mg/kg, respectively), while the liver had the highest values of Ag and Cu (0.8 and 100.9 mg/kg, respectively). Tissue Ag, Zn and Cd concentrations were similar to those found in green sea turtles from other regions while Cu and Pb values were elevated, likely due to the metal-rich water and sediment reported in the collection area. In the liver and kidney, concentrations of non-essential (Ag, Cd and Pb) and essential (Cu or Zn) metals were positively correlated, likely due to an induced metallothionein synthesis to protect tissue against the toxic effect of metals. This is the first study to report and correlate the concentrations of essential and non-essential metals in tissues of green sea turtles in the Brazilian southern Atlantic coast, an important feeding and developing area for this turtle species. - Highlights: •Juvenile female and male green sea turtles have similar concentrations of metals. •Kidney accumulated more Cd, Pb and Zn while liver accumulated more Ag and Cu. •Cu and Pb concentrations are elevated in liver of sea turtles from southern Brazil. •Concentrations of Cd and Cu in

  3. Interdependence of initial cell density, drug concentration and exposure time revealed by real-time impedance spectroscopic cytotoxicity assay

    DEFF Research Database (Denmark)

    Caviglia, Claudia; Zor, Kinga; Canepa, Silvia

    2015-01-01

    We investigated the combined effect of the initial cell density (12 500, 35 000, 75 000, and 100 000 cells cm−2) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing timedependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation...... between the rate of cell death and the initial cell seeding density was found at 2.5 μM doxorubicin concentration, whereas this was not observed at 5 or 100 μM. By sensing the changes in the cell–substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity...... was observed 5 h earlier than when using a standard colorimetric end-point assay (MTS) which measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay no cytotoxicity was observed after 15 h of incubation with 2.5 μM doxorubicin, whereas the impedance showed at this time point cell...

  4. Study of relationship of selenium concentration in blood components and tumor tissues of breast and GI tract cancers using neutron activation analysis technique

    International Nuclear Information System (INIS)

    Othman, I.; Bakir, M. A.; Yassine, T.; Sarhel, A.

    2001-12-01

    The purpose of this study was to investigate the relationship between selenium (Se) concentration in blood components and tumour tissues of breast and GI tract cancers using neutron activation analysis. red blood cell (RBC) and serum Se concentrations were determined in 50 healthy volunteers aged 25-84 years, 70 breast cancer patients aged 25-70 years and 34 GI tract cancer patients aged 31-85 years, Se levels were also determined in malignant and adjacent normal tissues from breast cancer and GI tract cancer patients. The results showed that Se concentrations in serum and RBC were significantly lower among breast and GI cancer compared to healthy volunteers. The results also showed that Se concentrations were significantly higher in the cancer tissues compared to adjacent normal tissues. These data have shown a relationship between selenium status in blood components and both cancer. selenium is enriched in cancer tissue, possibly in an effort of the body to inhibit the growth of tumours. (author)

  5. Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.

    Science.gov (United States)

    Vainionpää, Mari H; Raekallio, Marja R; Pakkanen, Soile A E; Ranta-Panula, Ville; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

    2013-05-01

    To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine. Experimental randomized blinded crossover study. Six healthy horses. Detomidine (10 μg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 μg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed ) and pharmacokinetic parameters. Significance was set at p Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance. MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  6. Concentrations of {sup 90}Sr in the tooth tissues 60 years after intake: results of TL measurements and applications for Techa River dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Shishkina, E.A.; Tolstykh, E.I.; Volchkova, A.Yu.; Degteva, M.O. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation); Verdi, E. [German Research Centre for Environmental Health, Helmholtz Zentrum Muenchen, Neuherberg (Germany); Veronese, I. [Universita degli Studi di Milano, Dipartimento di Fisica, Milan (Italy); INFN, Rome (Italy); El-Faramawy, N.A. [German Research Centre for Environmental Health, Helmholtz Zentrum Muenchen, Neuherberg (Germany); Ain Shams University, Department of Physics, Faculty of Science, Cairo (Egypt); Goeksu, H.Y. [German Research Centre for Environmental Health, Helmholtz Zentrum Muenchen, Neuherberg (Germany); Adiyaman University, Department of Physics, Faculty of Science and Art, Adiyaman (Turkey)

    2014-03-15

    This article focuses on the study of {sup 90}Sr in the tooth tissues of Techa riverside residents 60 years after intake. The Techa River was contaminated by radioactive wastes in the 1950s. Contamination of the river system, including water, bottom sediment, floodplain soil, and grass, depended on the distance from the source of releases. Therefore, the average {sup 90}Sr intake was different in different settlements located downstream the river. An additional factor influencing {sup 90}Sr accumulation in the teeth is the rate of tissue mineralization at the time of intake which depended on the donor's age at the time of releases. Measurements of {sup 90}Sr concentration in various dental tissues (enamel, crown, and root dentin) of 166 teeth were performed about 60 years after the main intake using the method of thermoluminescence passive beta detection. The paper presents the current levels of tooth tissue contamination, and the tooth-to-tooth variability of {sup 90}Sr concentration in tooth tissues was assessed for the tissues which were matured at the time of massive liquid radioactive waste releases into the Techa River. A model describing the expected levels of {sup 90}Sr in matured dental tissues depending on age and intake has been elaborated for the population under study. The results obtained will be used for calculation of internal dose in enamel and for interpretation of tooth doses measured by means of the electron paramagnetic resonance method, among the population of the Techa River region. (orig.)

  7. Ecotoxicoparasitology: Understanding mercury concentrations in gut contents, intestinal helminths and host tissues of Alaskan gray wolves (Canis lupus)

    Energy Technology Data Exchange (ETDEWEB)

    McGrew, Ashley K. [Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1619 (United States); O' Hara, Todd M. [Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1619 (United States); Wildlife Toxicology Laboratory, Department of Veterinary Medicine, University of Alaska Fairbanks, Fairbanks, AK 99775 (United States); Stricker, Craig A. [U. S. Geological Survey, Fort Collins Science Center, Denver, CO 80225 (United States); Margaret Castellini, J. [Wildlife Toxicology Laboratory, Department of Veterinary Medicine, University of Alaska Fairbanks, Fairbanks, AK 99775 (United States); Beckmen, Kimberlee B. [Alaska Department of Fish & Game, Fairbanks, AK (United States); Salman, Mo D. [Animal Population Health Institute, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523-1644 (United States); Ballweber, Lora R. [Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1619 (United States)

    2015-12-01

    Some gastrointestinal helminths acquire nutrients from the lumen contents in which they live; thus, they may be exposed to non-essential elements, such as mercury (Hg), during feeding. The objectives of this study were: 1) determine the total mercury concentrations ([THg]) in Gray wolves (Canis lupus) and their parasites, and 2) use stable isotopes to evaluate the trophic relationships within the host. [THg] and stable isotopes (C and N) were determined for helminths, host tissues, and lumen contents from 88 wolves. Sixty-three wolves contained grossly visible helminths (71.5%). The prevalence of taeniids and ascarids was 63.6% (56/88) and 20.5% (18/88), respectively. Nine of these 63 wolves contained both taeniids and ascarids (14.3%). All ascarids were determined to be Toxascaris leonina. Taenia species present included T. krabbei and T. hydatigena. Within the GI tract, [THg] in the lumen contents of the proximal small intestine were significantly lower than in the distal small intestine. There was a significant positive association between hepatic and taeniid [THg]. Bioaccumulation factors (BAF) ranged from < 1 to 22.9 in taeniids, and 1.1 to 12.3 in T. leonina. Taeniid and ascarid BAF were significantly higher than 1, suggesting that both groups are capable of THg accumulation in their wolf host. δ{sup 13}C in taeniids was significantly lower than in host liver and skeletal muscle. [THg] in helminths and host tissues, in conjunction with stable isotope (C and N) values, provides insight into food-web dynamics of the host GI tract, and aids in elucidating ecotoxicoparasitologic relationships. Variation of [THg] throughout the GI tract, and between parasitic groups, underscores the need to further evaluate the effect(s) of feeding niche, and the nutritional needs of parasites, as they relate to toxicant exposure and distribution within the host. - Highlights: • [THg] and stable isotopes together provide insight on host-parasite-Hg interactions. • A

  8. Ecotoxicoparasitology: Understanding mercury concentrations in gut contents, intestinal helminths and host tissues of Alaskan gray wolves (Canis lupus)

    International Nuclear Information System (INIS)

    McGrew, Ashley K.; O'Hara, Todd M.; Stricker, Craig A.; Margaret Castellini, J.; Beckmen, Kimberlee B.; Salman, Mo D.; Ballweber, Lora R.

    2015-01-01

    Some gastrointestinal helminths acquire nutrients from the lumen contents in which they live; thus, they may be exposed to non-essential elements, such as mercury (Hg), during feeding. The objectives of this study were: 1) determine the total mercury concentrations ([THg]) in Gray wolves (Canis lupus) and their parasites, and 2) use stable isotopes to evaluate the trophic relationships within the host. [THg] and stable isotopes (C and N) were determined for helminths, host tissues, and lumen contents from 88 wolves. Sixty-three wolves contained grossly visible helminths (71.5%). The prevalence of taeniids and ascarids was 63.6% (56/88) and 20.5% (18/88), respectively. Nine of these 63 wolves contained both taeniids and ascarids (14.3%). All ascarids were determined to be Toxascaris leonina. Taenia species present included T. krabbei and T. hydatigena. Within the GI tract, [THg] in the lumen contents of the proximal small intestine were significantly lower than in the distal small intestine. There was a significant positive association between hepatic and taeniid [THg]. Bioaccumulation factors (BAF) ranged from < 1 to 22.9 in taeniids, and 1.1 to 12.3 in T. leonina. Taeniid and ascarid BAF were significantly higher than 1, suggesting that both groups are capable of THg accumulation in their wolf host. δ 13 C in taeniids was significantly lower than in host liver and skeletal muscle. [THg] in helminths and host tissues, in conjunction with stable isotope (C and N) values, provides insight into food-web dynamics of the host GI tract, and aids in elucidating ecotoxicoparasitologic relationships. Variation of [THg] throughout the GI tract, and between parasitic groups, underscores the need to further evaluate the effect(s) of feeding niche, and the nutritional needs of parasites, as they relate to toxicant exposure and distribution within the host. - Highlights: • [THg] and stable isotopes together provide insight on host-parasite-Hg interactions. • A significant

  9. A tissue-engineered gastric cancer model for mechanistic study of anti-tumor drugs

    International Nuclear Information System (INIS)

    Gao, Ming; Cai, Yiting; Wu, Wei; Shi, Yazhou; Fei, Zhewei

    2013-01-01

    The use of the traditional xenograft subcutaneous tumor model has been contested because of its limitations, such as a slow tumorigenesis, inconsistent chemotherapeutic results, etc. In light of these challenges, we aim to revamp the traditional model by employing an electrospun scaffold composed of polydioxanone, gelatin and elastin to boost the tumorigenesis. The scaffold featured a highly porous microstructure and successfully supported the growth of tumor cells in vitro without provoking apoptosis. In vivo studies showed that in the scaffold model the tumor volume increased by 43.27% and the weight by 75.58%, respectively, within a 12-week period. In addition, the scaffold model saw an increase of CD24 + and CD44 + cells in the tumor mass by 42% and 313%, respectively. The scaffolding materials did not lead to phenotypic changes during the tumorigenesis. Thereafter, in the scaffold model, we found that the chemotherapeutic regimen of docetaxel, cisplatin and fluorouracil unleashed a stronger capability than the regimen comprising cisplatin and fluorouracil to deplete the CD44 + subpopulation. This discovery sheds mechanistic lights on the role of docetaxel for its future chemotherapeutic applications. This revamped model affords cancer scientists a convenient and reliable platform to mechanistically investigate the chemotherapeutic drugs on gastric cancer stem cells. (paper)

  10. Drug loaded homogeneous electrospun PCL/gelatin hybrid nanofiber structures for anti-infective tissue regeneration membranes.

    Science.gov (United States)

    Xue, Jiajia; He, Min; Liu, Hao; Niu, Yuzhao; Crawford, Aileen; Coates, Phil D; Chen, Dafu; Shi, Rui; Zhang, Liqun

    2014-11-01

    Infection is the major reason for guided tissue regeneration/guided bone regeneration (GTR/GBR) membrane failure in clinical application. In this work, we developed GTR/GBR membranes with localized drug delivery function to prevent infection by electrospinning of poly(ε-caprolactone) (PCL) and gelatin blended with metronidazole (MNA). Acetic acid (HAc) was introduced to improve the miscibility of PCL and gelatin to fabricate homogeneous hybrid nanofiber membranes. The effects of the addition of HAc and the MNA content (0, 1, 5, 10, 20, 30, and 40 wt.% of polymer) on the properties of the membranes were investigated. The membranes showed good mechanical properties, appropriate biodegradation rate and barrier function. The controlled and sustained release of MNA from the membranes significantly prevented the colonization of anaerobic bacteria. Cells could adhere to and proliferate on the membranes without cytotoxicity until the MNA content reached 30%. Subcutaneous implantation in rabbits for 8 months demonstrated that MNA-loaded membranes evoked a less severe inflammatory response depending on the dose of MNA than bare membranes. The biodegradation time of the membranes was appropriate for tissue regeneration. These results indicated the potential for using MNA-loaded PCL/gelatin electrospun membranes as anti-infective GTR/GBR membranes to optimize clinical application of GTR/GBR strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Estimation of polycyclic aromatic hydrocarbon concentrations in the water column based on tissue residues in mussels and salmon: An equilibrium partitioning approach

    International Nuclear Information System (INIS)

    Neff, J.M.; Burns, W.A.

    1996-01-01

    Equilibrium partitioning was used to estimate concentrations of dissolved polycyclic aromatic hydrocarbons (PAHs) in the water column from PAH residues in tissues of mussels and juvenile pink salmon collected from coastal marine waters affected by the Exxon Valdez oil spill. Estimated concentrations were within factors of 2 to 5 for fish and 5 to 10 for mussels of average total dissolved and particulate PAHs measured in concurrent water samples. Temporal trends of estimated and measured water-column PAH concentrations were comparable. Water-column PAH concentrations estimated from residues in tissues of mussels (Mytilus trossulus) were higher than estimates based on residues in tissues of juvenile pink salmon (Oncorhynchus gorbuscha). Possible reasons for this difference include seasonal variations in mussel lipid content, differences in PAH uptake and depuration rates between fish and mussels, differences in how fish and mussels interact with particulate oil, and possible short exposure times for juvenile pink salmon. All of these factors may play a role. In any event, estimates of dissolved PAHs in the water column, based on PAH residues in either fish or mussel tissue, confirm that PAH concentrations generally did not exceed water quality standards for protection of marine life

  12. Green Pharmaceutical Analysis of Drugs Coformulated with Highly Different Concentrations Using Spiking and Manipulation of Their Ratio Spectra.

    Science.gov (United States)

    Ayoub, Bassam M

    2017-07-01

    Introducing green analysis to pharmaceutical products is considered a significant approach to preserving the environment. This method can be an environmentally friendly alternative to the existing methods, accompanied by a validated automated procedure for the analysis of a drug with the lowest possible number of samples. Different simple spectrophotometric methods were developed for the simultaneous determination of empagliflozin (EG) and metformin (MT) by manipulating their ratio spectra in their application on a recently approved pharmaceutical combination, Synjardy tablets. A spiking technique was used to increase the concentration of EG in samples prepared from the tablets to allow for the simultaneous determination of EG with MT without prior separation. Validation parameters according to International Conference on Harmonization guidelines were acceptable over a concentration range of 2-12 μg/mL for both drugs using derivative ratio and ratio subtraction coupled with extended ratio subtraction. The optimized methods were compared using one-way analysis of variance and proved to be suitable as ecofriendly approaches for industrial QC laboratories.

  13. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    International Nuclear Information System (INIS)

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W; Emami, K; Wu, H

    2011-01-01

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  14. Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

    Science.gov (United States)

    Lamprou, Dimitrios A.; Venkatpurwar, Vinod; Kumar, M. N. V. Ravi

    2013-01-01

    Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ∼280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics. PMID:23724054

  15. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W [Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104 (United States); Emami, K; Wu, H, E-mail: sunwei@drexel.edu, E-mail: weisun@tsinghua.edu.cn [Radiation Biophysics Lab, NASA Johnson Space Center, Houston, TX 77586 (United States)

    2011-09-15

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  16. Receptor model for the molecular basis of tissue selectivity of 1,4-dihydropyridine calcium channel drugs

    Science.gov (United States)

    Langs, David A.; Strong, Phyllis D.; Triggle, David J.

    1990-09-01

    Our analysis of the solid state conformations of nifedipine [dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate] and its 1,4-dihydropyridine (1,4-DHP) analogues produced a cartoon description of the important interactions between these drugs and their voltage-dependent calcium channel receptor. In the present study a molecular-level detailed model of the 1,4-DHP receptor binding site has been built from the published amino acid sequence of the 215-1 subunit of the voltage-dependent calcium channel isolated from rabbit skeletal muscle transverse tubule membranes. The voltage-sensing component of the channel described in this work differs from others reported for the homologous sodium channel in that it incorporates a water structure and a staggered, rather than eclipsed, hydrogen bonded S4 helix conformation. The major recognition surfaces of the receptor lie in helical grooves on the S4 or voltagesensing α-helix that is positioned in the center of the bundle of transmembrane helices that define each of the four calcium channel domains. Multiple binding clefts defined by Arg-X-X-Arg-P-X-X-S `reading frames' exist on the S4 strand. The tissue selectivity of nifedipine and its analogues may arise, in part, from conservative changes in the amino acid residues at the P and S positions of the reading frame that define the ester-binding regions of receptors from different tissues. The crystal structures of two tissue-selective nifedipine analogues, nimodipine [isopropyl (2-methoxyethyl) 1,4-dihydro-2,6- dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] and nitrendipine [ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] are reported. Nimodipine was observed to have an unusual ester side chain conformation that enhances the fit to the proposed ester-sensing region of the receptor.

  17. Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus).

    Science.gov (United States)

    Lattin, Christine R; Romero, L Michael

    2014-07-15

    The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically stressed animal, suggesting that researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed either to a standardized chronic stress protocol (n=26) or to standard husbandry conditions (controls; n=20). We used radioligand binding assays to quantify receptors in whole brain, liver, kidneys, spleen, gonads, gastrocnemius and pectoralis muscle, omental and subcutaneous fat, and bib and back skin. In most tissues, CORT receptors did not differ between controls and stressed animals, although we found marginal increases in receptor density in kidney and testes in stressed birds at some time points. Only in pectoralis muscle was there a robust effect of chronic stress, with both receptor types higher in stressed animals. Increased pectoralis sensitivity to CORT with chronic stress may be part of the underlying mechanism for muscle wasting in animals administered exogenous CORT. Furthermore, the change in pectoralis was not paralleled by gastrocnemius receptors. This difference may help explain previous reports of a greater effect of CORT on pectoralis than on other muscle types, and indicate that birds use this muscle as a protein reserve. © 2014. Published by The Company of Biologists Ltd.

  18. Changes in the concentration of sulfhydryl groups in tissues of rats under the influence of gamma-radiation and adeturon

    International Nuclear Information System (INIS)

    Pantev, T.; Bychvarova, K.

    1984-01-01

    The concentration of SH-groups in the spleen, liver and bone marrow in rats was determined using the method of Sedlak and Lindsey. The changes in thiol level have been traced under the single influence of Adeturon and combined influence of radiation with 7,5 Gy and of Adeturon introduced 15 min before radiation. The animals were killed on 30th, 45th and 90th minute after the exerted influence. The control animals had physiological solution introduced. under the single influence of Adeturon there was increase in SH-groups mainly in the bone marrow in later terms after the exerted influence (the 90th minute), while P-SH in the spleen and liver decrease within the same term. The changes of NP-SH in the spleen and liver are opposite in nature. Under the influence of radiation P-SH in the liver and the spleen slightly decrease, while those in the bone marrow considerably increase on the 60th minute. NP-SH abruptly decrease on the 45th minute in the liver, while those in the spleen and bone marrow slightly differentiate from the control values. In animals protected by Adeturon P-SH in the bone marrow increase on the 30th and 45th minute, while those in the spleen decrease on the 90th minute. NP-SH decrease in the liver. The results obtained show that under the influence of Adeturon some changes occur in the level of thiols in tissues of both nonradiated and radiated animals

  19. Effects of CO 2 concentration and moisture content of sugar-free media on the tissue-cultured plantlets in a large growth chamber

    Science.gov (United States)

    Qu, Y. H.; Lin, C.; Zhou, W.; Li, Y.; Chen, B.; Chen, G. Q.

    2009-01-01

    The dynamic fluctuations of CO 2 concentration in the tissue culture growth chamber after transplantation of petunia, chrysanthemum and tomato plantlets were recorded with a real-time control system to determine the critical CO 2 concentration levels of 35 μl l -1 at which CO 2 enrichment is needed. The experimental data showed that the tissue-cultured plantlets of petunia, chrysanthemum and tomato had the same CO 2 concentration dynamics. The results indicated that CO 2 enrichment was proper on the second day after transplantation. Petunia plantlets were used to conduct experiments under PPFD of 80 μmol m -2 s -1, and CO 2 concentrations of 350 ± 50 μl l -1, 650 ± 50 μl l -1 and 950 ± 50 μl l -1 as well as medium moisture contents of 60%, 70% and 80%, with the result that plantlets grew better under CO 2 concentration of 650 ± 50 μl l -1 than under the other two concentrations with all the different media water contents. Three media water contents under the same CO 2 concentration produced plantlets with the same quality. The impacts of CO 2 concentrations on plantlets are more important than those of the media water contents. Sugar-free tissue culture, as compared with the conventional culture, showed that CO 2 enrichment to 350 ± 50 μl l -1 can promote the growth of the cultured plantlets. Sugar-free tissue culture produced healthy plantlets with thick roots, almost equivalent to the common plantlets.

  20. Hyaluronic acid based hydrogel system for soft tissue regeneration and drug delivery

    Science.gov (United States)

    Jha, Amit Kumar

    the gels. Human MSCs were undifferentiated during the early time points of culture, however differentiated into osteoblast phenotype after 28 days of culture. In summary, the HA-based hydrogel matrices are hierarchically structured, mechanically robust and enzymatically stable, capable of mediating cellular functions through the spatial and temporal presentation of defined biological cues. These hydrogel systems are promising candidates for soft tissue regeneration.

  1. Conjugated linoleic acid influences the metabolism of tocopherol in lactating rats but has little effect on tissue tocopherol concentrations in pups.

    Science.gov (United States)

    Zeitz, Johanna O; Most, Erika; Eder, Klaus

    2016-05-31

    Conjugated linoleic acid (CLA) is known to affect the lipid metabolism in growing and lactating animals. However, potential effects on the metabolism of fat-soluble vitamins in lactating animals and co-occurring effects on their offspring are unknown. We aimed to investigate the effects of dietary CLA on concentrations of tocopherol in various tissues of lactating rats and their offspring and expression of genes involved in tocopherol metabolism. Twenty-eight Wistar Han rats were allocated to 2 groups and fed either a control diet (control group) or a diet containing 0.9 % of cis-9, trans-11 and trans-10, cis-12 (1:1) CLA (CLA group) during pregnancy and lactation. Feed intake of dams and body weight of dams and their pups were recorded weekly. Tocopherol concentrations in various body tissues were determined at day 14 of lactation in dams and 1, 7 and 14 days after birth in pups. Expression of selected genes involved in metabolism of tocopherol was determined in dams and pups. The data were statistically analysed by analysis of variance. Feed intake and body weight development of nursing rats and their pups was similar in both groups. In livers of CLA-fed dams, tocopherol concentrations decreased by 24 % but expression of TTPA and CYP3A1, involved in tocopherol transport and metabolism, were not influenced. In the dams' adipose tissue, gene expression of receptors involved in tissue tocopherol uptake, LDLR and SCARB1, but not of LPL, increased by 30 to 50 % and tocopherol concentrations increased by 47 % in CLA-fed compared to control dams. Expression of LPL, LDLR and SCARB1 in mammary gland was not influenced by CLA-feeding. Tocopherol concentrations in the pup's livers and lungs were similar in both groups, but at 14 days of age, adipose tissue tocopherol concentrations, and LDLR and SCARB1 expression, were higher in the CLA-exposed pups. We show that dietary CLA affects tissue concentrations of tocopherol in lactating rats and tocopherol metabolism in

  2. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    International Nuclear Information System (INIS)

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-01-01

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  3. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  4. Soybean greatly reduces valproic acid plasma concentrations: A food–drug interaction study

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-01-01

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents. PMID:24618639

  5. Soybean greatly reduces valproic acid plasma concentrations: a food-drug interaction study.

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-03-12

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents.

  6. Serum concentrations of psychotropic drugs in neonates as a PROgnOstic Factor for admission to the neonatology ward and withdrawal symptoms: PROOF-1.

    Science.gov (United States)

    Sparla, Shirley C A; Coppens, Hans; Evers, Inge M; Stramrood, Claire A I; Pasker-de Jong, Pieternel C M; van der Westerlaken, Monique M L; Hogeman, Paul H G; Malingré, Mirte M

    2017-05-01

    The aim is to determine whether serum drug concentrations obtained from the neonate's umbilical cord can be used as a prognostic factor for admission to the neonatology ward and the occurrence of withdrawal symptoms. A retrospective observational monocenter cohort study was carried out among pregnant women using psychotropic drugs and their baby. Binary logistic regression was used for the multivariate analysis. Of the 186 neonates included, 22.6% (n=42) were admitted to the neonatology ward, 6.5% (n=12) because of withdrawal. Among women with therapeutic concentrations of psychotropic medication, 22.0% (n=5) of the neonates had withdrawal symptoms. When comparing neonates with therapeutic versus undetectable drug concentrations, an odds ratio of 3.1 (95% confidence interval: 1.1-8.6) was found for admission to the neonatology ward and an odds ratio of 20.5 (95% confidence interval: 2.2-186.1) for the occurrence of withdrawal symptoms. Therapeutic concentrations of psychotropic drugs in neonates' umbilical cord blood correspond with higher odds for admission to the neonatology ward and the occurrence of withdrawal symptoms compared with neonates with undetectable drug concentrations. The measurement of drug concentrations in the neonate may contribute toward the general clinical assessment of the physician to predict the necessity of admission to the neonatology ward and the risk of withdrawal symptoms.

  7. Evaluation of light scattering properties and chromophore concentrations in skin tissue based on diffuse reflectance signals at isosbestic wavelengths of hemoglobin

    Science.gov (United States)

    Yokokawa, Takumi; Nishidate, Izumi

    2016-04-01

    We investigate a method to evaluate light-scattering properties and chromophore concentrations in human skin tissue through diffuse reflectance spectroscopy using the reflectance signals acquired at isosbestic wavelengths of hemoglobin (420, 450, 500, and 585 nm). In the proposed method, Monte Carlo simulation-based empirical formulas are used to specify the scattering parameters of skin tissue, such as the scattering amplitude a and the scattering power b, as well as the concentration of melanin C m and the total blood concentration C tb. The use of isosbestic wavelengths of hemoglobin enables the values of C m, C tb, a, and b to be estimated independently of the oxygenation of hemoglobin. The spectrum of the reduced scattering coefficient is reconstructed from the scattering parameters. Experiments using in vivo human skin tissues were performed to confirm the feasibility of the proposed method for evaluating the changes in scattering properties and chromophore concentrations in skin tissue. The experimental results revealed that light scattering is significantly reduced by the application of a glycerol solution, which indicates an optical clearing effect due to osmotic dehydration and the matching of the refractive indices of scatterers in the epidermis.

  8. Real time monitoring of pulsatile change in hemoglobin concentrations of cerebral tissue by a portable tissue oximeter with a 10-Hz sampling rate

    Science.gov (United States)

    Shiga, Toshikazu; Chihara, Eiichi; Tanabe, Kazuhisa; Tanaka, Yoshifumi; Yamamoto, Katsuyuki

    1998-01-01

    A portable CW tissue oximeter of a 10-Hz sampling rate was developed for examination of pulsatile components of the output signals as a mean of checking the signal reliability during long-term monitoring. Feasible studies were performed on a healthy subject. Changes in Hb and HbO2 signals of cerebral tissue were continuously measured by placing a photoprobe on the forehead during 6-hour sleep. Pulsatile changes in Hb and HbO2 were steadily observed over a whole period of the recording. The phase relation of pulsation in Hb and HbO2 was almost inverse. Not only information for reliable monitoring but also physiological parameters with respect to cerebral circulation and metabolism could be obtained by measuring the pulsatile components.

  9. Kinetic Behaviour of Glucose 6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase in Different Tissues of Rainbow Trout (Oncorhynchus mykiss Exposed to Non-Lethal Concentrations of Cadmium

    Directory of Open Access Journals (Sweden)

    Olcay Hisar

    2009-01-01

    Full Text Available The effects of cadmium (Cd on the enzymatic activities of glucose 6-phosphate dehydrogenase (G6PD and 6-phosphogluconate dehydrogenase (6PGD were investigated in the gill, liver and kidney tissues of rainbow trout (Oncorhynchus mykiss. Three test groups of fish were subjected to increasing concentrations (1, 3 and 5 mg/l of cadmium (Cd in vivo, respectively. The G6PD and 6PGD activities in the gill, liver, and kidney tissues of each group of fish were measured on days 1, 3, 5 and 7. G6PD and 6PGD enzyme activities, measured in gill, liver and kidney homogenates, were stimulated by various concentrations (1, 3, and 5 mg/l of cadmium. Although the dose-response pattern of G6PD enzyme activities in liver and kidney tissue was very similar, that in gill was different from both other tissues. The enzyme activity of G6PD enzyme was significantly stimulated after three days (Day 3 in liver and kidney tissues at a dose of 1 mg/l Cd (p p p p p p < 0.05 in liver and kidney tissues at the doses of 3 and 1 mg/l Cd. The stimulation effect of cadmium on the three tissues studied was also calculated; for both of the enzymes (G6PD and 6PGD, the enzyme activity levels were stimulated by approximately 60% and 38% in gills, 68% and 44% in liver, and 67% and 41% in kidneys, respectively, over the base-line enzyme activity of the control groups during the sevenday experimental period. These findings indicate that tissue G6PD and 6PGD enzymes function to protect against cadmium toxicity.

  10. Study of the specific activity concentrations of 40K, {sup 226}Ra, {sup 228}Ra and {sup 232}Th in vegetables and their respective covering tissues (peels)

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, J.M.; Garcêz, R.W.D., E-mail: marqueslopez@yahoo.com.br [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Silva, A.X. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Escola Politécnica

    2017-07-01

    This work presents an analysis of specific concentrations of {sup 40}K, {sup 226}Ra, {sup 228}Ra and {sup 232}Th in some vegetables that are part of the diet of the population of the state of Rio de Janeiro. Furthermore, was analyzed the concentrations of radionuclides in the same coating tissue that compose the vegetables. It can notice an increase of the specific concentration of {sup 40}K in the peels of vegetables that have little or no contact with the ground. Among the samples examined, only the pumpkin showed measurable amount of {sup 137}Cs both saves and in the skin. (author)

  11. Study of the specific activity concentrations of 40K, 226Ra, 228Ra and 232Th in vegetables and their respective covering tissues (peels)

    International Nuclear Information System (INIS)

    Lopes, J.M.; Garcêz, R.W.D.; Silva, A.X.

    2017-01-01

    This work presents an analysis of specific concentrations of 40 K, 226 Ra, 228 Ra and 232 Th in some vegetables that are part of the diet of the population of the state of Rio de Janeiro. Furthermore, was analyzed the concentrations of radionuclides in the same coating tissue that compose the vegetables. It can notice an increase of the specific concentration of 40 K in the peels of vegetables that have little or no contact with the ground. Among the samples examined, only the pumpkin showed measurable amount of 137 Cs both saves and in the skin. (author)

  12. Effects of calcium disodium EDTA and meso-2,3-dimercaptosuccinic acid on tissue concentrations of lead for use in treatment of calves with experimentally induced lead toxicosis.

    Science.gov (United States)

    Meldrum, James B; Ko, Kam W

    2003-06-01

    To compare the efficacy of calcium disodium EDTA (CaNa2EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) in reducing concentrations of lead in selected tissues for use in treatment of calves with experimentally induced lead toxicosis. 19 sexually intact male Holstein calves that weighed 35 to 60 kg. Calves were randomly assigned to 1 of 5 treatment groups: group 1, control calves; group 2, lead only; group 3, lead and EDTA; group 4, lead and DMSA; and group 5, lead, EDTA, and DMSA. Calves in groups 2 to 5 were dosed daily with lead (5 mg/kg, PO) for 10 days. Doses of EDTA (100 mg/kg) and DMSA (25 mg/kg) were administered IV once daily for 4 consecutive days beginning on day 11. Effects of the chelators on lead concentrations in the liver, kidneys, testes, muscles, bones, and brain were compared among the various groups. Compared with the effects of EDTA, DMSA greatly reduced lead concentrations in renal and hepatic tissues. We did not detect significant differences for the effects of EDTA or DMSA on lead concentrations in the testes; there was an adverse interaction of EDTA with DMSA that caused an increase in lead concentrations in the testes. DMSA is much more effective than EDTA in removing lead from renal and hepatic tissues in calves. Use of DMSA in calves with lead intoxication appears to be a viable treatment option. Combining DMSA and EDTA as a treatment modality in calves did not offer any advantages.

  13. Concentrations of metallic elements in kidney, liver, and lung tissue of Indo-Pacific bottlenose dolphin Tursiops aduncus from coastal waters of Zanzibar, Tanzania.

    Science.gov (United States)

    Mapunda, Edgar C; Othman, Othman C; Akwilapo, Leonard D; Bouwman, Hindrik; Mwevura, Haji

    2017-09-15

    Concentrations of metallic elements in kidney, liver and lung tissues of Indo-Pacific bottlenose dolphins Tursiops aduncus from coastal waters of Zanzibar were determined using inductively coupled plasma - optical emission spectroscopy. Cadmium, chromium, copper, and zinc were quantifiable in all tissues at concentration ranges of 0.10-150, 0.08-3.2, 1.1-88 and 14-210μg/g dry mass, respectively. Copper and zinc was significantly higher in liver, and females had significantly higher Cd in liver, and chromium in lung. Generally, T. aduncus dolphins from coastal waters around Zanzibar carry low concentrations of metals compared with dolphins from other areas. Cadmium increased significantly with age in kidney and lung. Copper decreased significantly with age in liver, probably due to foetal metallothionein. This study supplied baseline data against which future trends in marine mammals in the Indian Ocean, the world's third largest, can be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs.

    Science.gov (United States)

    Yu, Hong; Bao, En-Dong; Zhao, Ru-Qian; Lv, Qiong-Xia

    2007-11-01

    To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs. 24 pigs (mean weight, 20 +/- 1 kg). Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA. No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs. Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.

  15. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Science.gov (United States)

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  16. Capacity of the aquatic fern (Salvinia minima Baker) to accumulate high concentrations of nickel in its tissues, and its effect on plant physiological processes

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes, Ignacio I.; Espadas-Gil, Francisco; Talavera-May, Carlos; Fuentes, Gabriela; Santamaría, Jorge M., E-mail: jorgesm@cicy.mx

    2014-10-15

    Highlights: • We document the capacity of an aquatic fern to hyper-accumulate Ni. • Effects of high Ni concentrations uptake on plant performance is documented. • High concentration of Ni in tissues damage photosynthesis. • Damage is related to carboxylation mechanisms than to electron transfer efficiency. • S. minima is a good candidate for remediation of water bodies contaminated with Ni. - Abstract: An experiment was designed to assess the capacity of Salvinia minima Baker to uptake and accumulate nickel in its tissues and to evaluate whether or not this uptake can affect its physiology. Our results suggest that S. minima plants are able to take up high amounts of nickel in its tissues, particularly in roots. In fact, our results support the idea that S. minima might be considered a hyper-accumulator of nickel, as it is able to accumulate 16.3 mg g{sup −1} (whole plant DW basis). Our results also showed a two-steps uptake pattern of nickel, with a fast uptake of nickel at the first 6 to 12 h of being expose to the metal, followed by a slow take up phase until the end of the experiment at 144 h. S. minima thus, may be considered as a fern useful in the phytoremediation of residual water bodies contaminated with this metal. Also from our results, S. minima can tolerate fair concentrations of the metal; however, at concentrations higher than 80 μM Ni (1.5 mg g{sup −1} internal nickel concentration), its physiological performance can be affected. For instance, the integrity of cell membranes was affected as the metal concentration and exposure time increased. The accumulation of high concentrations of internal nickel did also affect photosynthesis, the efficiency of PSII, and the concentration of photosynthetic pigments, although at a lower extent.

  17. Concentration of labelled polyphosphates in soft tissue lesions. Application to the study of cerebral and myocardial infarction

    International Nuclear Information System (INIS)

    Guillemart, Alain.

    1975-01-01

    The biological behavior and tissue localization of phosphorus compounds used in Nuclear Medicine are reviewed. The mechanism of skeletal localization is emphasized. Labeled pyrophosphate compounds have proved extremely useful for skeletal imaging, however the mechanism of increased accumulation of these agents has been observed also in soft tissues. They localize in the acutely infarcted myocardium and in brain lesions. Clinical results obtained with sup(99m)Tc stannous pyrophosphate in brain and myocardium imaging are reported [fr

  18. The effect of non-steroidal anti-inflammatory drugs on the metabolism of /sup 14/C-arachidonic acid by human gingival tissue in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Elattar, T.M.; Lin, H.S.; Tira, D.E.

    1983-09-01

    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with /sup 14/C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam.

  19. The effect of non-steroidal anti-inflammatory drugs on the metabolism of 14C-arachidonic acid by human gingival tissue in vitro

    International Nuclear Information System (INIS)

    Elattar, T.M.; Lin, H.S.; Tira, D.E.

    1983-01-01

    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with 14 C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam

  20. Spectral filtering modulation method for estimation of hemoglobin concentration and oxygenation based on a single fluorescence emission spectrum in tissue phantoms.

    Science.gov (United States)

    Liu, Quan; Vo-Dinh, Tuan

    2009-10-01

    Hemoglobin concentration and oxygenation in tissue are important biomarkers that are useful in both research and clinical diagnostics of a wide variety of diseases such as cancer. The authors aim to develop simple ratiometric method based on the spectral filtering modulation (SFM) of fluorescence spectra to estimate the total hemoglobin concentration and oxygenation in tissue using only a single fluorescence emission spectrum, which will eliminate the need of diffuse reflectance measurements and prolonged data processing as required by most current methods, thus enabling rapid clinical measurements. The proposed method consists of two steps. In the first step, the total hemoglobin concentration is determined by comparing a ratio of fluorescence intensities at two emission wavelengths to a calibration curve. The second step is to estimate oxygen saturation by comparing a double ratio that involves three emission wavelengths to another calibration curve that is a function of oxygen saturation for known total hemoglobin concentration. Theoretical derivation shows that the ratio in the first step is linearly proportional to the total hemoglobin concentrations and the double ratio in the second step is related to both total hemoglobin concentration and hemoglobin oxygenation for the chosen fiber-optic probe geometry. Experiments on synthetic fluorescent tissue phantoms, which included hemoglobin with both constant and varying oxygenation as the absorber, polystyrene spheres as scatterers, and flavin adenine dinucleotide as the fluorophore, were carried out to validate the theoretical prediction. Tissue phantom experiments confirm that the ratio in the first step is linearly proportional to the total hemoglobin concentration and the double ratio in the second step is related to both total hemoglobin concentrations and hemoglobin oxygenation. Furthermore, the relations between the two ratios and the total hemoglobin concentration and hemoglobin oxygenation are insensitive

  1. Effects of different concentrations of Platelet-rich Plasma and Platelet-Poor Plasma on vitality and differentiation of autologous Adipose tissue-derived stem cells.

    Science.gov (United States)

    Felthaus, Oliver; Prantl, Lukas; Skaff-Schwarze, Mona; Klein, Silvan; Anker, Alexandra; Ranieri, Marco; Kuehlmann, Britta

    2017-01-01

    Autologous fat grafts and adipose-derived stem cells (ASCs) can be used to treat soft tissue defects. However, the results are inconsistent and sometimes comprise tissue resorption and necrosis. This might be due to insufficient vascularization. Platelet-rich plasma (PRP) is a source of concentrated autologous platelets. The growth factors and cytokines released by platelets can facilitate angiogenesis. The simultaneous use of PRP might improve the regeneration potential of fat grafts. The optimal ratio has yet to be elucidated. A byproduct of PRP preparation is platelet-poor plasma (PPP). In this study we investigated the influence of different concentrations of PRP on the vitality and differentiation of ASCs. We processed whole blood with the Arthrex Angel centrifuge and isolated ASCs from the same donor. We tested the effects of different PRP and PPP concentrations on the vitality using resazurin assays and the differentiation of ASCs using oil-red staining. Both cell vitality and adipogenic differentiation increase to a concentration of 10% to 20% PRP. With a PRP concentration of 30% cell vitality and differentiation decrease. Both PRP and PPP can be used to expand ASCs without xenogeneic additives in cell culture. A PRP concentration above 20% has inhibitory effects.

  2. Effect of laser wavelength and protein solder concentration on acute tissue repair using laser welding: initial results in a canine ureter model.

    Science.gov (United States)

    Wright, E J; Poppas, D P

    1997-01-01

    Successful tissue approximation can be performed using low power laser energy combined with human albumin solder. In vitro studies were undertaken to investigate the acute repair strengths achieved using different laser wavelengths. Furthermore, we evaluated the change in repair strength with that resulted from changes in protein solder concentration. Intraluminal bursting pressure following ureterotomy repair was measured for the following laser wavelengths: 532, 808, 1,320, 2,100, and 10,600 nm. The tissue absorption characteristics of the 808-nm diode and the KTP-532-nm lasers required the addition of the exogenous chromophores indocyanine green and fluorescein, respectively. A 40% human albumin solder was incorporated in the repair of a 1.0-cm longitudinal defect in the canine ureter. Following determination of an optimal welding wavelength, human albumin solder of varying concentrations (25%, 38%, 45%, and 50%) were prepared and tested. The 1,320-nm YAG laser achieved the highest acute bursting pressure and was the most effective in this model. Of the concentrations of albumin tested, 50% human albumin yielded the greatest bursting pressures. We conclude that of the laser wavelengths evaluated, the 1,320-nm YAG achieves the strongest tissue weld in the acute ex vivo dog ureter model. In addition, when this laser system is used, the acute strength of a photothermal weld appears to be directly proportional to the concentration of human albumin solder in the range of 25 to 50%.

  3. Boron concentration measurements by alpha spectrometry and quantitative neutron autoradiography in cells and tissues treated with different boronated formulations and administration protocols

    International Nuclear Information System (INIS)

    Bortolussi, Silva; Ciani, Laura; Postuma, Ian; Protti, Nicoletta; Luca Reversi,; Bruschi, Piero; Ferrari, Cinzia; Cansolino, Laura; Panza, Luigi; Ristori, Sandra; Altieri, Saverio

    2014-01-01

    The possibility to measure boron concentration with high precision in tissues that will be irradiated represents a fundamental step for a safe and effective BNCT treatment. In Pavia, two techniques have been used for this purpose, a quantitative method based on charged particles spectrometry and a boron biodistribution imaging based on neutron autoradiography. A quantitative method to determine boron concentration by neutron autoradiography has been recently set-up and calibrated for the measurement of biological samples, both solid and liquid, in the frame of the feasibility study of BNCT. This technique was calibrated and the obtained results were cross checked with those of α spectrometry, in order to validate them. The comparisons were performed using tissues taken form animals treated with different boron administration protocols. Subsequently the quantitative neutron autoradiography was employed to measure osteosarcoma cell samples treated with BPA and with new boronated formulations. - Highlights: • A method for 10B measurements in samples based on neutron autoradiography was developed. • The results were compared with those of alpha spectrometry applied on tissue and cell samples. • Boronated liposomes were developed and administered to osteosarcoma cell cultures. • Neutron autoradiography was employed to measure boron concentration due to liposomes. • Liposomes were proved to be more effective in concentrating boron in cells than BPA

  4. Drugs in breast milk.

    Science.gov (United States)

    Hervada, A R; Feit, E; Sagraves, R

    1978-09-01

    The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

  5. Anal submucosal injection: a new route for drug administration in pelvic malignancies. Part I. Experimental study of misonidazole distribution in serum and tissues, with special reference to urinary bladder. Preliminary report

    International Nuclear Information System (INIS)

    Shafik, A.; el-Merzabani, M.M.; el-Aaser, A.A.; el-Desouky, G.H.

    1986-01-01

    The anal and oral administration routes were compared in 30 rats to study the distribution of misonidazole, a radiation sensitizer, in the serum and tissues with special reference to the urinary bladder. 14C-labelled misonidazole was administered in a dose of 0.2 ml water/100 gm body weight containing 1 mu Ci misonidazole. The dose was given orally by stomach tube in 15 rats, and was injected in the submucosa of the anal canal in another 15. Animals were then killed after 15, 30, 60, or 120 minutes or after 24 hours. Organs were dissected, and radioactivity was determined in each by the internal standard method. The study has shown that the highest drug concentration in the bladder tissue relative to the serum was achieved with the anal submucosal route. Its level was eight and five times that of the serum 15 and 30 minutes after administration, respectively, in contrast to the oral route in which the drug concentration was one-quarter and equal to the serum level at the same time intervals. The anal route would thus provide the adequate channel required for misonidazole to promote radiation responsiveness in bladder carcinoma

  6. Anthropogenic impacts on mercury concentrations and nitrogen and carbon isotope ratios in fish muscle tissue of the Truckee River watershed, Nevada, USA

    International Nuclear Information System (INIS)

    Sexauer Gustin, Mae; Saito, Laurel; Peacock, Mary

    2005-01-01

    The lower Truckee River originates at Lake Tahoe, California/Nevada (NV), USA and ends in the terminal water body, Pyramid Lake, NV. The river has minimal anthropogenic inputs of contaminants until it encounters the cities of Reno and Sparks, NV, and receives inflows from Steamboat Creek (SBC). SBC originates at Washoe Lake, NV, where there were approximately six mills that used mercury for gold and silver amalgamation in the late 1800s. Since then, mercury has been distributed down the creek to the Truckee River. In addition, SBC receives agricultural and urban nonpoint source pollution, and treated effluent from the Reno-Sparks water reclamation facility. Fish muscle tissue was collected from different species in SBC and the Truckee River and analyzed for mercury and stable isotopes. Nitrogen (?δ 15 N) and carbon (?δ 13 C) isotopic values in these tissues provide insight as to fish food resources and help to explain their relative Hg concentrations. Mercury concentrations, and ?δ 15 N and ?δ 13 C values in fish muscle from the Truckee River, collected below the SBC confluence, were significantly different than that found in fish collected upstream. Mercury concentrations in fish tissue collected below the confluence for all but three fish sampled were significantly greater (0.1 to 0.65 μg/g wet wt.) than that measured in the tissue collected above the confluence (0.02 to 0.1 μg/g). ?δ 15 N and ?δ 13 C isotopic values of fish muscle collected from the river below the confluence were higher and lower, respectively, than that measured in fish collected up river, most likely reflecting wastewater inputs. The impact of SBC inputs on muscle tissue isotope values declined down river whereas the impact due to Hg inputs showed the opposite trend

  7. Macro- and micro-nutrient concentration in leaf, woody, and root tissue of Populus irrigated with landfill leachate

    Science.gov (United States)

    Jill A. Zalesny; Ronald S., Jr. Zalesny; Adam H. Wiese; Bart T. Sexton; Richard B. Hall

    2007-01-01

    Landfill leachate offers an opportunity to supply water and plant nutritional benefits at a lower cost than traditional sources. Information about nutrient uptake and distribution into tissues of Populus irrigated with landfill leachate helps increase biomass production along with evaluating the impacts of leachate chemistry on tree health.

  8. Quantitative determination of localized tissue oxygen concentration in vivo by two-photon excitation phosphorescence lifetime measurements

    NARCIS (Netherlands)

    Mik, Egbert G.; van Leeuwen, Ton G.; Raat, Nicolaas J.; Ince, Can

    2004-01-01

    This study describes the use of two-photon excitation phosphorescence lifetime measurements for quantitative oxygen determination in vivo. Doubling the excitation wavelength of Pd-porphyrin from visible light to the infrared allows for deeper tissue penetration and a more precise and confined

  9. Short and long term modulation of tissue minerals concentrations following oral administration of black cumin (Nigella sativa L.) seed oil to laboratory rats.

    Science.gov (United States)

    Basheer, Irum; Qureshi, Irfan Zia

    2018-01-15

    Nigella sativa, or commonly called black cumin is a small herb of family Ranunculaceae is a well-known medicinal plant but its effects on tissue mineral concentrations of animal bodies is unknown. To study the effect of oral administration of fixed oil of black cumin seeds on tissues mineral content using laboratory rats as experimental model. Experimental animals were exposed to two oral doses of seed oil (60 and 120 ml kg -1 body weight). Short- and long term experiments lasted 24 h and 60 days respectively, with three replicates each. Oil extracted from black cumin seeds was subjected to GC-MS to identify chemical components. Following the wet digestion in nitric acid, samples of whole blood and organs of rats were subjected to atomic absorption spectrophotometry for determination of elements concentrations. Data were compared statistically at p < .05. Compared to control, Cr, Mn, Ni, Cu, Zn showed decrease, whereas Co, Na, Mg and K demonstrated increase, but Ca showed both increase and decrease in most of the tissues upon short term exposure to low and high doses of black cumin oil. During long term exposure, Cr, Fe, Mn, Cu exhibited decrease; Co, Na, Mg and Ca concentrations demonstrated an upregulation, whereas Ni and Zn showed increase and decrease in most of the tissues. Comparison of short term with long term experiments at low dose revealed increases in Fe, Zn, Cu, Mg, K and Ca, a decrease in Cr, Mn, Ni and Cu in most tissues, but both increase and decrease in Na. At high dose, an increase occurred in Fe, Ni, Zn, K, Ca, Mg, a decrease in Cr, while both increase and decrease in Cu, Co and Na concentrations. Our study demonstrates that oral administration of black cumin seeds oil to laboratory rats significantly alters tissue trace elements and electrolytes concentrations. The study appears beneficial but indicates modulatory role of black cumin oil as regards mineral metabolism with far reaching implications in health and disease. Copyright © 2017

  10. NADH-fluorescence scattering correction for absolute concentration determination in a liquid tissue phantom using a novel multispectral magnetic-resonance-imaging-compatible needle probe

    Science.gov (United States)

    Braun, Frank; Schalk, Robert; Heintz, Annabell; Feike, Patrick; Firmowski, Sebastian; Beuermann, Thomas; Methner, Frank-Jürgen; Kränzlin, Bettina; Gretz, Norbert; Rädle, Matthias

    2017-07-01

    In this report, a quantitative nicotinamide adenine dinucleotide hydrate (NADH) fluorescence measurement algorithm in a liquid tissue phantom using a fiber-optic needle probe is presented. To determine the absolute concentrations of NADH in this phantom, the fluorescence emission spectra at 465 nm were corrected using diffuse reflectance spectroscopy between 600 nm and 940 nm. The patented autoclavable Nitinol needle probe enables the acquisition of multispectral backscattering measurements of ultraviolet, visible, near-infrared and fluorescence spectra. As a phantom, a suspension of calcium carbonate (Calcilit) and water with physiological NADH concentrations between 0 mmol l-1 and 2.0 mmol l-1 were used to mimic human tissue. The light scattering characteristics were adjusted to match the backscattering attributes of human skin by modifying the concentration of Calcilit. To correct the scattering effects caused by the matrices of the samples, an algorithm based on the backscattered remission spectrum was employed to compensate the influence of multiscattering on the optical pathway through the dispersed phase. The monitored backscattered visible light was used to correct the fluorescence spectra and thereby to determine the true NADH concentrations at unknown Calcilit concentrations. Despite the simplicity of the presented algorithm, the root-mean-square error of prediction (RMSEP) was 0.093 mmol l-1.

  11. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

    Directory of Open Access Journals (Sweden)

    Rančić Nemanja

    2015-01-01

    Full Text Available Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872 of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster

  12. Comparison of drug distribution images from whole-body thin tissue sections obtained using desorption electrospray ionization tandem mass spectrometry and autoradiography.

    Science.gov (United States)

    Kertesz, Vilmos; Van Berkel, Gary J; Vavrek, Marissa; Koeplinger, Kenneth A; Schneider, Bradley B; Covey, Thomas R

    2008-07-01

    Desorption electrospray ionization tandem mass spectrometry (DESI-MS/MS) and whole-body autoradiography (WBA) were used for chemical imaging of whole-body thin tissue sections of mice intravenously dosed with propranolol (7.5 mg/kg). DESI-MS/MS imaging utilized selected reaction monitoring detection performed on an AB/MDS SCIEX 4000 QTRAP mass spectrometer equipped with a prototype extended length particle discriminator interface. Propranolol images of the tissue sections using DESI-MS/MS were obtained at surface scan rates of 0.1, 0.5, 2, and 7 mm/s. Although signal decreased with increasing scan rate, useful whole-body images for propranolol were obtained from the tissues even at 7 mm/s, which required just 79 min of analysis time. Attempts to detect and image the distribution of the known propranolol metabolites were unsuccessful. Regions of the tissue sections showing the most radioactivity from WBA sections were excised and analyzed by high-performance liquid chromatography (HPLC) with radiochemical detection to determine relative levels of propranolol and metabolites present. Comparison of the DESI-MS/MS signal for propranolol and the radioactivity attributed to propranolol from WBA sections indicated nominal agreement between the two techniques for the amount of propranolol in the brain, lung, and liver. Data from the kidney showed an unexplained disparity between the two techniques. The results of this study show the feasibility of using DESI-MS/MS to obtain useful chemical images of a drug in whole-body thin tissue sections following drug administration at a pharmacologically relevant level. Further optimization to improve sensitivity and enable detection of the drug metabolites will be among the requirements necessary to move DESI-MS/MS chemical imaging forward as a practical tool in drug discovery.

  13. Effect of Different Concentrations of Growth Regulators on Gardenia jasminoides cv. Veitchii Micropropagation by Tissue Culture Technique

    Directory of Open Access Journals (Sweden)

    G. R. Abdullah

    2003-01-01

    Full Text Available Micropropagation techniques were set up for Gardenia jasminoides c.v. veitchi. Many plantlets were obtained by culturing shoot cuttings in MS nutrient media, 30 g/L Sucrose, 7 g/L Agar Agar, and different concentrations of BAP and IAA. The best concentration was 1mg /L BAP with 0.5 mg/L IAA. This concentration gave the best sprout growth suitable for rooting in primary and secondary culture by reculturing the stuck cutting every 6 weeks and for many times. We also obtained a high rooting percentage up to 98 % of natural rooting in rooting media different from propagation media by reducing mineral salt concentration to half, Sucrose to 20gm/L, and 2gm/L active charcoal, and 1mg/L IAA. Plantlets were transferred to greenhous and subjected for hardening. This technique gave 22 plantlets from one cutting in one year.

  14. Radioanalytical methods for the measurement of melanin concentrating hormone (MCH) and detection its receptor in rat tissues

    International Nuclear Information System (INIS)

    Lelesz, B.; Szilvassy, Z.; Varga, A.; Juhasz, B.; Nemeth, J.; Toth, G.K.; Toth, A.; Enyedi, A.; Felszeghy, E.

    2016-01-01

    In the present paper the development and application of a novel melanin concentrating hormone radioimmunoassay and receptor-binding assay are described. 125 I-labeling of melanin concentrating hormone (MCH) was performed by iodogen and the mono-iodinated peptide was separated by reversed-phase high performance liquid chromatography. Detection limit of the MCH specific assay was 0.2 fmol/ml. As a practical application of the novel radioimmunoassay, we measured the MCH concentration in different rat organs. High MCH concentrations were detected in the small intestine, pancreas, kidney, liver, trachea, hypothalamus and spinal cord. 125 I-MCH was also suitable for RBA to demonstrate the presence of MCH receptors in the rat brain. (author)

  15. Air pollution assessment based on elemental concentration of leaves tissue and foliage dust along an urbanization gradient in Vienna.

    Science.gov (United States)

    Simon, Edina; Braun, Mihály; Vidic, Andreas; Bogyó, Dávid; Fábián, István; Tóthmérész, Béla

    2011-05-01

    Foliage dust contains heavy metal that may have harmful effects on human health. The elemental contents of tree leaves and foliage dust are especially useful to assess air environmental pollution. We studied the elemental concentrations in foliage dust and leaves of Acer pseudoplatanus along an urbanization gradient in Vienna, Austria. Samples were collected from urban, suburban and rural areas. We analysed 19 elements in both kind of samples: aluminium, barium, calcium, copper, iron, potassium, magnesium, sodium, phosphor, sulphur, strontium and zinc. We found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for aluminium, barium, iron, lead, phosphor and selenium. Elemental concentrations of leaves were significantly higher in urban than in rural area for manganese and strontium. Urbanization changed significantly the elemental concentrations of foliage dust and leaves and the applied method can be useful for monitoring the environmental load. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Air pollution assessment based on elemental concentration of leaves tissue and foliage dust along an urbanization gradient in Vienna

    International Nuclear Information System (INIS)

    Simon, Edina; Braun, Mihaly; Vidic, Andreas; Bogyo, David; Fabian, Istvan; Tothmeresz, Bela

    2011-01-01

    Foliage dust contains heavy metal that may have harmful effects on human health. The elemental contents of tree leaves and foliage dust are especially useful to assess air environmental pollution. We studied the elemental concentrations in foliage dust and leaves of Acer pseudoplatanus along an urbanization gradient in Vienna, Austria. Samples were collected from urban, suburban and rural areas. We analysed 19 elements in both kind of samples: aluminium, barium, calcium, copper, iron, potassium, magnesium, sodium, phosphor, sulphur, strontium and zinc. We found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for aluminium, barium, iron, lead, phosphor and selenium. Elemental concentrations of leaves were significantly higher in urban than in rural area for manganese and strontium. Urbanization changed significantly the elemental concentrations of foliage dust and leaves and the applied method can be useful for monitoring the environmental load. - Highlights: → We studied the elements in dust and leaves along an urbanization gradient, Austria. → We analysed 19 elements: Al, Ba, Ca, Cd, Cu, Fe, K, Mg, Na, P, Pb, S, Sr and Zn. → Elemental concentrations were higher in urban area than in the rural area. → Studied areas were separated by CDA based on the elemental concentrations. → Dust and leaves can be useful for monitoring the environmental load. - Studying the elements (Al, Ba, Ca, Cu, Fe, K, Mg, Na, P, S, Sr, Zn) in dust and leaves along an urbanization gradient in Wien, Austria we found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for Al, Ba, Fe, Pb, P and Se, and concentrations of leaves were significantly higher in urban than in rural area for Mn and Sr.

  17. Air pollution assessment based on elemental concentration of leaves tissue and foliage dust along an urbanization gradient in Vienna

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Edina, E-mail: edina.simon@gmail.com [Department of Ecology, University of Debrecen, H-4010 Debrecen, P.O. Box 71 (Hungary); Braun, Mihaly [Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, P.O. Box 21 (Hungary); Vidic, Andreas [Department fuer Naturschutzbiologie, Vegetations- und Landschaftsoekologie, Universitat Wien, Althanstrasse 14, 1090 Wien (Austria); Bogyo, David [Department of Ecology, University of Debrecen, H-4010 Debrecen, P.O. Box 71 (Hungary); Fabian, Istvan [Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, P.O. Box 21 (Hungary); Tothmeresz, Bela [Department of Ecology, University of Debrecen, H-4010 Debrecen, P.O. Box 71 (Hungary)

    2011-05-15

    Foliage dust contains heavy metal that may have harmful effects on human health. The elemental contents of tree leaves and foliage dust are especially useful to assess air environmental pollution. We studied the elemental concentrations in foliage dust and leaves of Acer pseudoplatanus along an urbanization gradient in Vienna, Austria. Samples were collected from urban, suburban and rural areas. We analysed 19 elements in both kind of samples: aluminium, barium, calcium, copper, iron, potassium, magnesium, sodium, phosphor, sulphur, strontium and zinc. We found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for aluminium, barium, iron, lead, phosphor and selenium. Elemental concentrations of leaves were significantly higher in urban than in rural area for manganese and strontium. Urbanization changed significantly the elemental concentrations of foliage dust and leaves and the applied method can be useful for monitoring the environmental load. - Highlights: > We studied the elements in dust and leaves along an urbanization gradient, Austria. > We analysed 19 elements: Al, Ba, Ca, Cd, Cu, Fe, K, Mg, Na, P, Pb, S, Sr and Zn. > Elemental concentrations were higher in urban area than in the rural area. > Studied areas were separated by CDA based on the elemental concentrations. > Dust and leaves can be useful for monitoring the environmental load. - Studying the elements (Al, Ba, Ca, Cu, Fe, K, Mg, Na, P, S, Sr, Zn) in dust and leaves along an urbanization gradient in Wien, Austria we found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for Al, Ba, Fe, Pb, P and Se, and concentrations of leaves were significantly higher in urban than in rural area for Mn and Sr.

  18. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy

    International Nuclear Information System (INIS)

    Gray, L.H.; Conger, A.D.; Ebert, M.; Hornsey, S.; Scott, O.C.A.

    1984-01-01

    The sensitivity of tumour cells to X rays has been shown to be about three times as great when irradiated in a well-oxygenated medium as under anoxic conditions. The manner in which sensitivity depends on oxygen tension closely resembles that found by other workers for plant and insect tissues. The sensitivity of the tumour cells to fast neutron radiation is only slightly affected by oxygen tension. Consideration is given to the supply of oxygen to tissues as a factor in radiotherapy, and it is concluded on the basis of existing knowledge that in certain circumstances the effectiveness of X-ray treatment might be increased if the patient were breathing oxygen at the time of irradiation

  19. Effects of Biotin Supplementation in the Diet on Adipose Tissue cGMP Concentrations, AMPK Activation, Lipolysis, and Serum-Free Fatty Acid Levels.

    Science.gov (United States)

    Boone-Villa, Daniel; Aguilera-Méndez, Asdrubal; Miranda-Cervantes, Adriana; Fernandez-Mejia, Cristina

    2015-10-01

    Several studies have shown that pharmacological concentrations of biotin decrease hyperlipidemia. The molecular mechanisms by which pharmacological concentrations of biotin modify lipid metabolism are largely unknown. Adipose tissue plays a central role in lipid homeostasis. In the present study, we analyzed the effects of biotin supplementation in adipose tissue on signaling pathways and critical proteins that regulate lipid metabolism, as well as on lipolysis. In addition, we assessed serum fatty acid concentrations. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (control: 1.76 mg biotin/kg; supplemented: 97.7 mg biotin/kg diet) over 8 weeks postweaning. Compared with the control group, biotin-supplemented mice showed an increase in the levels of adipose guanosine 3',5'-cyclic monophosphate (cGMP) (control: 30.3±3.27 pmol/g wet tissue; supplemented: 49.5±3.44 pmol/g wet tissue) and of phosphorylated forms of adenosine 5'-monophosphate-activated protein kinase (AMPK; 65.2%±1.06%), acetyl-coenzyme A (CoA), carboxylase-1 (196%±68%), and acetyl-CoA carboxylase-2 (78.1%±18%). Serum fatty acid concentrations were decreased (control: 1.12±0.04 mM; supplemented: 0.91±0.03 mM), and no change in lipolysis was found (control: 0.29±0.05 μmol/mL; supplemented: 0.33±0.08 μmol/mL). In conclusion, 8 weeks of dietary biotin supplementation increased adipose tissue cGMP content and protein expression of the active form of AMPK and of the inactive forms of acetyl-CoA carboxylase-1 and acetyl-CoA carboxylase-2. Serum fatty acid levels fell, and no change in lipolysis was observed. These findings provide insight into the effects of biotin supplementation on adipose tissue and support its use in the treatment of dyslipidemia.

  20. Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

    Directory of Open Access Journals (Sweden)

    Stenman Ulf-Håkan

    2011-08-01

    Full Text Available Abstract Background We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI in both tumour tissue (t-TATI and in serum (s-TATI are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT on concentrations of t-TATI and s-TATI in patients with rectal cancer. Methods TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term preoperative RT and 21 patients 25 × 2 Gy (long-term preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. Results RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P Conclusions The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.

  1. Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.

    Science.gov (United States)

    Guiastrennec, Benjamin; Ramachandran, Geetha; Karlsson, Mats O; Kumar, A K Hemanth; Bhavani, Perumal Kannabiran; Gangadevi, N Poorana; Swaminathan, Soumya; Gupta, Amita; Dooley, Kelly E; Savic, Radojka M

    2017-12-16

    This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4-7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P unfavorable ). Model-based simulation of optimized (P unfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure-response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines. © 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  2. Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype

    DEFF Research Database (Denmark)

    Buchard, Anders; Linnet, Kristian; Johansen, Sys Stybe

    2010-01-01

    We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S-enantiome......We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S...

  3. Effects of Tissue Culture and Mycorrhiza Applications in Organic Farming on Concentrations of Phytochemicals and Antioxidant Capacities in Ginger (Zingiber officinale Roscoe) Rhizomes and Leaves.

    Science.gov (United States)

    Min, Byungrok R; Marsh, Lurline E; Brathwaite, Keegan; Daramola, Adebola O

    2017-04-01

    Tissue culture and mycorrhiza applications can provide disease-free seedlings and enhanced nutrient absorption, respectively, for organic farming. Ginger (Zingiber officinale Roscoe) is rich in phytochemicals and has various health-protective potentials. This study was aimed at determining effects of tissue culture and mycorrhiza applications alone or in combinations in organic farming on phytochemical contents (total phenolics and flavonoids [TP and TF, respectively], gingerol and shogaol homologues, phenolic acids, and carotenoids) and antioxidant capacities (DPPH [2,2-diphenyl-1-picrylhydrazyl] radical scavenging, oxygen radical absorbance (ORAC), and iron-chelating capacities [ICC]) in solvent-extractable (Free) and cell-wall-matrix-bound (Bound) fractions of ginger rhizome and Free fraction of the leaves in comparison with non-organics. Concentrations of the phytochemicals and antioxidant capacities, except for carotenoids and ICC, were significantly higher in organic ginger rhizomes and leaves than in non-organics regardless of the fractions and treatments (P < 0.05). Mycorrhiza application in organic farming significantly increased levels of TP, TF, gingerols, and ORAC in the Free fraction of the rhizome (P < 0.05). Furthermore, the combined application of tissue culture and mycorrhiza significantly increased concentrations of TF and gingerols and ORAC in the Free fraction of the rhizome (P < 0.05), suggesting their synergistic effects. Considerable amounts of phenolics were found in the Bound fractions of the rhizomes. Six-gingerol, ferulic acid, and lutein were predominant ones among gingerols, phenolic acids, and carotenoids, respectively, in ginger rhizomes. The results suggest that organic farming with mycorrhiza and tissue culture applications can increase concentrations of phytochemicals and antioxidant capacities in ginger rhizomes and leaves and therefore improve their health-protective potentials. © 2017 Institute of Food Technologists®.

  4. Analyses of Selenotranscriptomes and Selenium Concentrations in Response to Dietary Selenium Deficiency and Age Reveal Common and Distinct Patterns by Tissue and Sex in Telomere-Dysfunctional Mice.

    Science.gov (United States)

    Cao, Lei; Zhang, Li; Zeng, Huawei; Wu, Ryan Ty; Wu, Tung-Lung; Cheng, Wen-Hsing

    2017-10-01

    Background: The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity. Objective: We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice. Methods: Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo. Plasma, hearts, kidneys, livers, and testes were collected to assay for selenotranscriptomes, selected selenoproteins, and tissue selenium concentrations. Data were analyzed with the use of 2-factor ANOVA (diet × age) in both sexes. Results: Dietary selenium deficiency decreased ( P ≤ 0.05) selenium concentrations (65-72%) and glutathione peroxidase (GPX) 3 (82-94%) and selenoprotein P (SELENOP) (17-41%) levels in the plasma of both sexes of mice and mRNA levels (9-68%) of 4, 4, and 12 selenoproteins in the heart, kidney, and liver of males, respectively, and 5, 16, and 14 selenoproteins, respectively, in females. Age increased selenium concentrations and SELENOP levels (27% and 30%, respectively; P ≤ 0.05) in the plasma of males only but decreased (12-46%; P selenium deficiency and age in ≥1 tissue or sex, or both. Dietary selenium deficiency upregulated (40-160%; P ≤ 0.05) iodothyronine deiodinase 2 ( Dio2 ) and selenoprotein N ( Selenon ) in the kidneys of males. Age upregulated (11-44%; P selenium status and selenotranscriptomes because of dietary selenium deficiency and age. © 2017 American Society for Nutrition.

  5. Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

    Science.gov (United States)

    Navarro, M; Pichini, S; Farré, M; Ortuño, J; Roset, P N; Segura, J; de la Torre, R

    2001-10-01

    Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

  6. Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans

    DEFF Research Database (Denmark)

    Orskov, C; Rabenhøj, L; Wettergren, A

    1994-01-01

    Using specific radioimmunoassays, we studied the occurrence of amidated and glycine-extended glucagon-like peptide I (GLP-I) molecules in the human small intestine and pancreas and in the circulation system in response to a breakfast meal. Through gel permeation chromatography of extracts...... plasma were 7 +/- 1 and 6 +/- 1 pM, respectively (n = 6). In response to a breakfast meal, the concentration of amidated GLP-I rose significantly amounting to 41 +/- 5 pM 90 min after the meal ingestion, whereas the concentration of glycine-extended GLP-I only rose slightly to a maximum of 10 +/- 1 p...

  7. Parallel monitoring of plasma and intraluminal drug concentrations in man after oral administration of fosamprenavir in the fasted and fed state.

    Science.gov (United States)

    Brouwers, Joachim; Tack, Jan; Augustijns, Patrick

    2007-10-01

    The purpose of this study was to explore the feasibility of linking the pharmacokinetic profile of a drug with its gastrointestinal behavior by simultaneously monitoring plasma and intraluminal drug concentrations. Fosamprenavir, a phosphate ester prodrug of the poorly water-soluble HIV-inhibitor amprenavir, was selected as model compound. A single tablet of fosamprenavir (Telzir) was administered to 5 volunteers in the fasted and fed state (simulated by intake of a nutritional drink). Gastric and duodenal fluids were aspirated in function of time and characterized with respect to the concentration of (fos)amprenavir, inorganic phosphate and pH. In parallel, blood samples were collected and analyzed for amprenavir. The observed plasma concentration-time profiles suggested a food-induced delay in the absorption of amprenavir: in the fed state, mean tmax increased by more than 150 min compared to the fasted state. A similar delay was seen in the duodenal appearance of fosamprenavir (concentrations in mM-range) and, after dephosphorylation, amprenavir (concentrations below 160 microM). This observation could be related to the behavior of fosamprenavir in the stomach. In the fasted state, gastric dissolution of fosamprenavir started immediately, resulting in a Cmax of 4 +/- 2 mM after 43 +/- 15 min; however, in the fed state, the fosamprenavir concentration remained below 20 microM for the first 90 min after drug intake. The postponed gastric dissolution may be attributed to a food-induced delay in tablet disintegration. For the first time, the pharmacokinetic profile of a drug was monitored in parallel with its gastrointestinal concentrations. The observed food effect in the plasma concentration-time profile of amprenavir after intake of its phosphate ester prodrug could be related to a food-induced delay in gastric dissolution of fosamprenavir.

  8. Serotonin concentrations in platelets, plasma, mitral valve leaflet, and left ventricular myocardial tissue in dogs with myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Cremer, Signe Emilie; Singletary, G.E.; Olsen, Lisbeth Høier

    2014-01-01

    HYPOTHESIS/OBJECTIVES: Altered serotonin (5-hydroxytryptamine, 5HT) signaling is postulated in development and progression of canine myxomatous mitral valve disease (MMVD). Little is known regarding platelet, plasma, valvular, or myocardial 5HT concentration ([5HT]) in affected dogs. We quantifie...

  9. Does low protein concentration of tissue-type plasminogen activator predict a low risk of spontaneous deep vein thrombosis?

    DEFF Research Database (Denmark)

    Gram, J; Sidelmann, Johannes Jakobsen; Jespersen, J

    1995-01-01

    activity (p Reasonable separation could be obtained for t-PA with a cut-off point of 5...... interval 70%-94%). We observed a significantly negative association between concentration of t-PA and fibrinolytic activity (rs = -0.47; p WORDS)...

  10. Mecury in Fin Clips and Scales as Assessment Methods for Predicting Muscle Tissue Mercury Concentrations in Red Drum and Snook

    Science.gov (United States)

    Non-lethal techniques for assessing total mercury concentrations in fish are desired because they minimize impacts on fish populations and allow trends in Hg accumulation to be assessed through repeated sampling of individual fish. This study developed relationships of Hg concent...

  11. Can tissue element concentration patterns at the individual-species level indicate the factors underlying vegetation gradients in wetlands?

    Czech Academy of Sciences Publication Activity Database

    Rozbrojová, Zuzana; Hájek, M.

    2010-01-01

    Roč. 21, č. 2 (2010), s. 355-363 ISSN 1100-9233 Institutional research plan: CEZ:AV0Z60050516 Keywords : plant nutrient concentration * vegetation gradient * wetland vegetation Subject RIV: EF - Botanics Impact factor: 2.457, year: 2010

  12. Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients

    Directory of Open Access Journals (Sweden)

    Verde Roberta

    2010-04-01

    Full Text Available Abstract Background The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT of subjects with both obesity and type 2 diabetes (OBT2D, characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB. Design and Methods The levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA and palmitoylethanolamide (PEA, in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p Conclusions The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners and 2-AG in obesity and type 2 diabetes.

  13. Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

    Science.gov (United States)

    Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

    2015-09-01

    The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry

    NARCIS (Netherlands)

    Berm, E; Kok, R.; Hak, E; Wilffert, B

    2016-01-01

    Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the

  15. Differences in trace element concentrations between Alzheimer and 'normal' human brain tissue using instrumental neutron activation analysis (INAA)

    International Nuclear Information System (INIS)

    Panayi, A.E.; Spyrou, N.M.

    2001-01-01

    Brain samples obtained from the Netherlands Brain Bank were taken from the superior frontal gyrus, superior parietal gyrus and medial temporal gyrus of 'normal' and Alzheimer's disease subjects in order to determine elemental concentrations and compare elemental composition. Brain samples from the cortex were taken from 18 subjects, eight 'normals' (6 males and 2 females) and eleven with Alzheimer's disease, (1 male and 10 females) and the following elemental concentrations, Na, K, Fe, Zn, Se, Br, Rb, Ag, Cs, Ba, and Eu were determined by instrumental neutron activation analysis (INAA). The element which showed the greatest difference was Br, which was found to be significantly elevated in the cortex of Alzheimer's disease brains as compared to the 'normals' at significance (p < 0.001). (author)

  16. Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

    International Nuclear Information System (INIS)

    Gaber, Alexander; Jirström, Karin; Stene, Christina; Hotakainen, Kristina; Nodin, Björn; Palmquist, Ingrid; Bjartell, Anders; Stenman, Ulf-Håkan; Jeppsson, Bengt; Johnson, Louis B

    2011-01-01

    We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer. TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term) preoperative RT and 21 patients 25 × 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0

  17. Chlorophenol and alkylphenol concentrations in sediment and mussel tissues collected from selected locations in Kentucky Lake, USA

    Energy Technology Data Exchange (ETDEWEB)

    Loganathan, B.; Brown, B.; Owen, D. [Murray State Univ., Murray, KY (United States); Sajwan, K. [Savannah State Univ., Savannah, GA (United States)

    2004-09-15

    Kentucky (KY) Lake is one the major human-constructed lakes in the US. It serves as an ultimate repository of substances entering this watershed from portions of seven southeastern states, which include a sizeable fraction of the U.S. chemical processing, agricultural chemical products and electronics manufacturing industries. Although a few studies have examined the levels of chlorinated organics in the KY Lake and the lowermost Tennessee River, there have been no reports on the distribution on the levels of chlorophenols and alkylphenols in sediment and/or biological tissues from this region. In this study, sediment, and freshwater mussels were collected from selected locations in KY Lake and Lake Barkley and analyzed for CPs and APs. Furthermore, wood samples from abandoned docks, navigational towers and wood found in the lake bottom were also analyzed to examine the sources of CPs to the lakes.

  18. Reduced glutathione concentration and glutathione reductase activity in various rat tissues after the administration of some radioprotective agents

    International Nuclear Information System (INIS)

    Pulpanova, J.; Kovarova, H.; Ledvina, M.

    1982-01-01

    The concentrations of reduced glutathione (GSH) and activity of glutathione reductase were investigated in rat liver, kidney and spleen after intraperitoneal administration of cystamine (50 mg/kg), mexamine (10 mg/kg), or a mixture of cystamine with mexamine (20 + 10 mg/kg). The GSH concentration increased after the administration of cystamine in the liver (maximum between the 20th and 30th min), in the kidney and spleen (maximum after 60 min). The cystamine + mexamine mixture also caused a significant increase of the GSH concentration in all the organs investigated; however, the values increased at earlier intervals as after the cystamine administration. No substantial effect was shown in the case of the mexamine administration, only 30 min after the administration the values were higher. The activity of glutathione reductase was significantly lower over the entire period examined. This was found in the liver and kidney as after the administration of cystamine, as after the radioprotective mixture. There was also a less pronounced inhibition of the enzyme activity in the spleen. Mexamine as a single radioprotector had practically no influence on the activity. (author)

  19. Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations.

    Science.gov (United States)

    ElSharawy, Abdou; Röder, Christian; Becker, Thomas; Habermann, Jens K; Schreiber, Stefan; Rosenstiel, Philip; Kalthoff, Holger

    2016-11-15

    The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls.Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible "strand-specific" deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease.Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics.

  20. Trace element concentrations in leachates and mustard plant tissue (Sinapis alba L.) after biochar application to temperate soils.

    Science.gov (United States)

    Kloss, Stefanie; Zehetner, Franz; Oburger, Eva; Buecker, Jannis; Kitzler, Barbara; Wenzel, Walter W; Wimmer, Bernhard; Soja, Gerhard

    2014-05-15

    Biochar application to agricultural soils has been increasingly promoted worldwide. However, this may be accompanied by unexpected side effects in terms of trace element (TE) behavior. We used a greenhouse pot experiment to study the influence of woodchip-derived biochar (wcBC) on leaching and plant concentration of various TEs (Al, Cd, Cu, Pb, Mn, As, B, Mo, Se). Three different agricultural soils from Austria (Planosol, Cambisol, Chernozem) were treated with wcBC at application rates of 1 and 3% (w/w) and subsequently planted with mustard (Sinapis alba L.). Soil samples were taken 0 and 7 months after the start of the pot experiment, and leachate water was collected twice (days 0 and 54). The extractability (with NH4NO3) of cationic TEs was decreased in the (acidic) Planosol and Cambisol after wcBC application, whereas in the (neutral) Chernozem it hardly changed. In contrast, anionic TEs were mobilized in all three soils, which resulted in higher anion concentrations in the leachates. The application of wcBC had no effect on Al and Pb in the mustard plants, but increased their B and Mo concentrations and decreased their Cd, Cu and Mn concentrations. A two-way analysis of variance showed significant interactions between wcBC application rate and soil type for most TEs, which indicates that different soil types may react differently upon wcBC application. Correlation and partial correlation analyses revealed that TE behavior was primarily related to soil pH, whereas the involvement of other factors such as electrical conductivity (EC), organic carbon (OC) content and dissolved organic carbon (DOC) was found to be more soil and TE-specific. The application of wcBC may be a useful strategy for the remediation of soils with elevated levels of cationic TEs, but could lead to deficiencies of cationic micronutrients and enhance short-term translocation of anionic TEs towards the groundwater at high leaching rates. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Polychlorinated biphenyl concentrations, congener profiles, and ratios in the fat tissue, eggs, and plasma of snapping turtles (Chelydra s. serpentina) from the Ohio Basin of Lake Erie, USA.

    Science.gov (United States)

    Dabrowska, H; Fisher, S W; Estenik, J; Kidekhel, R; Stromberg, P

    2006-08-01

    Concentrations and profiles of polychlorinated biphenyls (PCBs) were determined in three tissues of adult snapping turtles (Chelydra serpentina serpentina) from six locations in the Ohio Basin of Lake Erie to characterize tissue variation and geographic trends. The locations included the Ohio Areas of Concern, i.e., the Ashtabula, Black, and Maumee Rivers; the Ottawa River near Toledo; and two reference sites. Mean total PCBs were greatest in turtles from the Ottawa River followed by the Maumee, Ashtabula, and Black Rivers. All three types of samples-fat tissue (FT), eggs, and plasma-showed the same geographic trend in PCB levels. On a wet-weight basis, mean concentrations ranged from 2,148 to 18,669 ng/g in FT, from 183 to 3,683 ng/g in eggs, and from 18 to 201 ng/g in plasma. Across all sites, total PCB concentrations between the tissues were significantly correlated (0.001 40 congeners (0.001 < p < 0.05). The distribution ratios determined for these congeners from the slope of the regression lines averaged 1.235 +/- 0.279, 0.430 +/- 0.170, and 0.387 +/- 0.115, respectively. The plasma wet weight-FT lipid-normalized concentration ratios for these congeners averaged 0.012 +/- 0.006. Both egg-FT and plasma wet weight-FT lipid-normalized ratios regressed against log K(ow) showed significant decreases, with increasing log K(ow), indicating greater accumulation of highly chlorinated congeners in FT than in other compartments. The estimated 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents ranged from 0.007 ng/g at reference sites to 0.060 ng/g at contaminated sites and from 0.099 to 1.992 ng/g in plasma and eggs, respectively. In both plasma and eggs, coplanar-CBs were the major contributors to total toxic equivalents (TEQs). Eggs from all contaminated sites had TEQs that exceeded the lowest observed effect level TEQs proposed for bald eagle chicks, in addition to high SigmaPCB levels at some of these sites, especially the Ottawa and Maumee River sites, indicate

  2. Tissue Mercury Concentrations and Survival of Tree Swallow Embryos, Nestlings and Young Adult Females on a Contaminated Site.

    Science.gov (United States)

    Taylor, Capwell E; Cristol, Daniel A

    2015-10-01

    Tree swallows nesting on mercury-contaminated sites along the South River in Virginia, USA were monitored for reproductive success. The bodies of nestlings found deceased in their nest boxes were collected, along with blood and feather samples from the adult parents and surviving siblings. We also measured hatching and fledging success of the clutches and the annual recapture rate of adults. We found that the body feathers of deceased nestlings contained significantly higher concentrations of mercury (12.89 ± 8.42 μg/g, n = 15) than those of nestlings that survived to fledge (7.41 ± 4.79 μg/g, n = 15). However, mothers of more successful clutches (>75 % hatching) did not differ in mercury concentrations from females with less successful clutches (<50 % hatching). Additionally, adult females breeding for the first time that returned to breed the following year did not differ in blood mercury from females of the same age that bred once but never returned. Our results suggest that mercury had its greatest effect on these songbirds during the nestling stage, whereas for embryos or first-time breeding females, other factors likely played larger roles in mortality.

  3. Mechanism of tumor and liver concentration of /sup 67/Ga: /sup 67/Ga binding substances in tumor tissues and liver

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A; Ando, I; Hiraki, T; Takeshita, M; Hisada, K

    1983-01-01

    Tumor-bearing animals were administered with /sup 67/Ga citrate and tumor homogenates, from which nuclear fraction was removed, and mitochondrial fraction of the host livers were digested with protease (pronase P). After digestion, the supernatants of the reaction mixtures were applied to a Sephadex G-100 column. Resultant eluates were analyzed for radioactivity, protein, uronic acid and sialic acids. Three peaks of radioactivity were obtained by gel filtration. The first peak eluted in the void volume contained a species whose molecular weight exceeded 40,000. The second peak consisted of substances with molecular weights of 9400-40,000. Radioactivity in the third peak was from liberated gallium-67. /sup 67/Ga in the second peak was bound to acid mucopolysaccharide and/or the sulfated carbohydrate chain of sulfated glycoprotein. It was thought that /sup 67/Ga in the first peak might be bound to some acid mucopolysaccharides. Considering the results of cellulose acetate electrophoresis, /sup 67/Ga in the second peak seemed to be bound to acid mucopolysaccharide which contained no uronic acids, and/or to the sulfated carbohydrate chain of sulfated glycoprotein. It was concluded that /sup 67/Ga was bound to the acid mucopolysaccharides and/or the sulfated carbohydrate chain of sulfated glycoprotein in tumor tissues and liver lysosomes.

  4. On the search for new anticancer drugs 14: the plasma pharmacokinetics and tissue distribution of spin-labeled thio-TEPA (SL-O-TT).

    Science.gov (United States)

    Gutierrez, P L; Cohen, B E; Sosnovsky, G; Davis, T A; Egorin, M J

    1985-01-01

    We defined the plasma and tissue concentrations and pharmacokinetics of SL-O-TT, a spin-labeled analog of thio-TEPA, in 35-44-g male Swiss Webster mice that had received spin-labeled thio-TEPA at a dosage of 10 mg/kg. Concentrations of spin-labeled thio-TEPA in ethyl acetate extracts of tissue and plasma were determined by gas-liquid chromatography and electron spin resonance spectroscopy. Plasma concentrations of spin-labeled thio-TEPA declined in a biexponential fashion that was well described by the equation: Ct = 21.5e-0.276t + 2.30e-0.026t indicating a half-life alpha of 2.5 min and a half-life beta of 26.6 min. After 2 h there was still spin-labeled thio-TE-PA in plasma, but not in tissues. In tissues, no spin-labeled thio-TEPA was detected with gas-liquid chromatography 15 min after injection, but with electron-spin resonance label was found in lung and skeletal muscle. The main metabolite of spin-labeled thio-TEPA is spin-labeled TEPA, where oxidative desulfurization is invoked as the main metabolic mechanism. Reduction of the spin label to the hydroxylamine was also observed with time.

  5. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  6. Postmortem concentrations of gamma-hydroxybutyrate (GHB) in peripheral blood and brain tissue - Differentiating between postmortem formation and antemortem intake

    DEFF Research Database (Denmark)

    Thomsen, Ragnar; Rasmussen, Brian Schou; Johansen, Sys Stybe

    2017-01-01

    to fermentation processes. The endogenous nature of GHB leads to difficulty in interpretation of concentrations, as the source of GHB is not obvious. Postmortem brain and blood samples were collected from 221 individuals at autopsy. Of these, 218 were not suspected of having ingested GHB, while GHB intake....../kg (median 15.3mg/kg) in blood and not-detected to 9.8mg/kg (median 4.8mg/kg) in brain tissue. For case A, where intoxication with GHB was deemed to be the sole cause of death, the concentrations were 199 and 166mg/kg in blood and brain, respectively. For case B, where intoxication with GHB...

  7. Effect of sucrose concentration and gamma irradiation on growth and essential oil composition of spearmint plant through tissue culture

    International Nuclear Information System (INIS)

    El-Sharnouby, M.E.

    2007-01-01

    In vitro culture of spearmint plant (Mentha spicata L) using different sucrose concentrations and different gamma irradiation treatments was investigated. The shoot tips of spearmint plant were cultured on MS medium without hormones and supplemented with different concentrations of sucrose (10, 20, 30 and 40 g/l) then exposed to different gamma irradiation treatments (2,4,6 and 8 Krad) to determine their effects on growth and chemical composition in different sub-culturing media . The data showed that culturing shoots of Mentha spicata on MS medium containing 10 g/l sucrose produced the highest values of callus than other treatments and the maximum number of shoots was produced on MS medium supplemented with 20 g/l sucrose. Irradiation of spearmint shoots at 8 Krad when cultured on MS medium containing 30 or 40 g/l sucrose caused minimum number of shoots, whereas the longest shoots were produced with MS medium containing 20 g/l sucrose after irradiation at 60 Gy gamma dose. Treating shoots of Mentha spicata by gamma irradiation at 8 Krad and culturing on MS medium containing 30 g/l sucrose produced all sub-cultures in shortest length of shoots. Moreover, adding 40 g/l of sucrose in MS medium gave the highest number of leaves than other treatments. Exposing shoots of spearmint plant to gamma irradiation at 8 Krad decreased the number of leaves when culturing on MS medium containing 10 or 30 g/l sucrose. Furthermore, the selected samples showed many differences on spearmint oil composition and proline content regarding sucrose levels and gamma irradiation doses

  8. Ultrastructural study of liver and lead tissue concentrations in young mallard ducks (Anas platyrhynchos) after ingestion of single lead shot.

    Science.gov (United States)

    Pineau, Alain; Fauconneau, Bernard; Plouzeau, Eric; Fernandez, Béatrice; Quellard, Nathalie; Levillain, Pierre; Guillard, Olivier

    2017-01-01

    Lead (Pb) represents a serious threat to wildlife and ecosystems. The aim of this study was to examine the subcellular effects of dietary Pb pellet ingestion on mallard (Anas platyrhynchos) livers. After ingestion of a single Pb shot (LS4 size class: 0.177 ± 0.03 g) in 41 mallard ducks (22 males and 19 females) versus 10 controls (5 males and 5 females), all 7-week old, a morphologic study was conducted by TEM (transmission electron microscopy) of liver at the subcellular level. The results in treated mallards showed at a magnification of 2500 X that hepatic parenchyma was altered as evidenced by intralysosomal electron-dense deposits, which are compatible with Pb deposits. Further, at a higher magnification (15,000 X) in both genders, deterioration of mitochondria was observed in which the crests and, to a lesser extent, outer membrane were lysed. While the rough endoplasmic reticulum was fragmented, intracytoplasmic electron-dense material compatible with Pb deposits was maximally visible, thereby underscoring the deeply destructive effect of this metal on the subcellular architecture of the liver. In addition, applying an optimized and validated method in a clean room using electrothermal atomic absorption spectrophotometer (ETAAS) with Zeeman background correction, the objective was to improve and refine certain indispensable measurements pertaining to Pb impregnation in tissues other than liver such as kidneys, bones, and feathers of mallards. Data demonstrated show that compared with controls, Pb accumulation increases significantly, not only in the liver (3-fold), but also in the bones and the feathers (14-fold). No significant difference was noted between males and females. Bearing in mind the marked subcellular toxicity attributed to Pb, this study reinforces present-day arguments advocating limitation of game consumption.

  9. Effects of 5,5'-diphenylhydantoin on thyroxine and 3,5,3'-triiodothyronine concentrations in several tissues of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder-van der Elst, J.Pv.; van der Heide, D. (University Hospital, Leiden (Netherlands))

    1990-01-01

    We studied the effect of 5,5'-diphenylhydantoin (phenytoin, DPH) on the metabolism of thyroid hormones, the intracellular concentration of T4, and the source and concentration of T3. Two groups of six male Wistar rats received a continuous infusion of 10 ml saline/rat. day. One group received DPH in their food (50 mg/kg BW) for 20 days. For both groups (125I)T4 and (131I)T3 were added to the infusion fluid for the last 10 and 7 days, respectively. At isotopic