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Sample records for healthy tissue tolerance

  1. Transcriptomes in healthy and diseased gingival tissues.

    Science.gov (United States)

    Demmer, Ryan T; Behle, Jan H; Wolf, Dana L; Handfield, Martin; Kebschull, Moritz; Celenti, Romanita; Pavlidis, Paul; Papapanou, Panos N

    2008-11-01

    Clinical and radiographic measures are gold standards for diagnosing periodontitis but offer little information regarding the pathogenesis of the disease. We hypothesized that a comparison of gene expression signatures between healthy and diseased gingival tissues would provide novel insights in the pathobiology of periodontitis and would inform the design of future studies. Ninety systemically healthy non-smokers with moderate to advanced periodontitis (63 with chronic periodontitis and 27 with aggressive periodontitis) each contributed at least two diseased interproximal papillae (with bleeding on probing [BOP], probing depth [PD] > or =4 mm, and attachment loss [AL] > or =3 mm) and a healthy papilla, if available (no BOP, PD < or =4 mm, and AL < or =2 mm). RNA was extracted, amplified, reverse-transcribed, labeled, and hybridized with whole genome microarrays. Differential expression was assayed in 247 individual tissue samples (183 from diseased sites and 64 from healthy sites) using a standard mixed-effects linear model approach, with patient effects considered random with a normal distribution and gingival tissue status considered a two-level fixed effect. Gene ontology analysis classified the expression patterns into biologically relevant categories. Transcriptome analysis revealed that 12,744 probe sets were differentially expressed after adjusting for multiple comparisons (P <9.15 x 10(7)). Of those, 5,295 were upregulated and 7,449 were downregulated in disease compared to health. Gene ontology analysis identified 61 differentially expressed groups (adjusted P <0.05), including apoptosis, antimicrobial humoral response, antigen presentation, regulation of metabolic processes, signal transduction, and angiogenesis. Gingival tissue transcriptomes provide a valuable scientific tool for further hypothesis-driven studies of the pathobiology of periodontitis.

  2. In situ FTIR assessment of desiccation-tolerant tissues

    NARCIS (Netherlands)

    Wolkers, W.F.; Hoekstra, F.A.

    2003-01-01

    This essay shows how Fourier transform infrared (FTIR) microspectroscopy can be applied to study thermodynamic parameters and conformation of endogenous biomolecules in desiccation-tolerant biological tissues. Desiccation tolerance is the remarkable ability of some organisms to survive complete dehy

  3. In situ FTIR assessment of desiccation-tolerant tissues

    NARCIS (Netherlands)

    Wolkers, W.F.; Hoekstra, F.A.

    2003-01-01

    This essay shows how Fourier transform infrared (FTIR) microspectroscopy can be applied to study thermodynamic parameters and conformation of endogenous biomolecules in desiccation-tolerant biological tissues. Desiccation tolerance is the remarkable ability of some organisms to survive complete dehy

  4. Gastrointestinal tolerance and utilization of agave inulin by healthy adults.

    Science.gov (United States)

    Holscher, Hannah D; Doligale, Jamie L; Bauer, Laura L; Gourineni, Vishnupriya; Pelkman, Christine L; Fahey, George C; Swanson, Kelly S

    2014-06-01

    Little clinical research exists on agave inulin as a fiber source. Due to differences in botanical origin and chemical structure compared to other inulin-type fibers, research is needed to assess gastrointestinal (GI) tolerance following consumption. This study aimed to evaluate GI tolerance and utilization of 5.0 and 7.5 g per day of agave inulin in healthy adults (n = 29) using a randomized, double-blind, placebo-controlled crossover trial consisting of three 21 day periods with 1 week washouts among periods. GI tolerance was assessed via daily and weekly questionnaires, three fecal samples were collected on days 16-20 of each period, and breath hydrogen testing was completed on the final day of each treatment period. Survey data were compared using a generalized linear mixed model. All other outcomes were analyzed using a mixed linear model with a repeated measures procedure. Composite GI intolerance scores for 5.0 and 7.5 g treatments were both greater (P agave inulin. Abdominal pain and rumbling intensity were marginally greater (P Agave inulin did not affect diarrhea (P > 0.05). Number of bowel movements per day increased, stools were softer, and stool dry matter percentage was lower with 7.5 g (P agave inulin compared to control. These data demonstrate that doses up to 7.5 g per day of agave inulin led to minimal GI upset, do not increase diarrhea, and improve laxation in healthy young adults.

  5. The relationship between water binding and desiccation tolerance in tissues

    Science.gov (United States)

    Vertucci, C. W.; Leopold, A. C.

    1987-01-01

    In an effort to define the nature of desiccation tolerance, a comparison of the water sorption characteristics was made between tissues that were resistant and tissues that were sensitive to desiccation. Water sorption isotherms were constructed for germinated and ungerminated soybean axes and also for fronds of several species of Polypodium with varying tolerance to dehydration. The strength of water binding was determined by van't Hoff as well as D'Arcy/Watt analyses of the isotherms at 5, 15, and/or 25 degrees C. Tissues which were sensitive to desiccation had a poor capacity to bind water tightly. Tightly bound water can be removed from soybean and pea seeds by equilibration at 35 degrees C over very low relative humidities; this results in a reduction in the viability of the seed. We suggest that region 1 water (i.e. water bound with very negative enthalpy values) is an important component of desiccation tolerance.

  6. Impaired Glucose Tolerance in Healthy Men Treated with St. John's Wort

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard

    2016-01-01

    The purpose of this study was to examine if the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions; A: Baseline, B: After 21 days...

  7. St. John's wort impairs glucose tolerance by reducing insulin response in healthy men

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard

    2015-01-01

    The purpose of this study was to examine if the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions; A: Baseline, B: After 21 days...

  8. Efficacy of Tissue Tolerable Plasma (TTP against Ixodes ricinus

    Directory of Open Access Journals (Sweden)

    Bender, Claudia

    2014-03-01

    Full Text Available [english] The efficacy of Tissue Tolerable Plasma (TTP against ticks was tested, as data from the literature has demonstrated its efficacy against other acari.The study was carried out by using the KINPen09 (Argon as carrier gas on (n=24. Treatment times of 1 and 3 minutes led to a reversible inactivation of the ticks. After 5 min of treatment, they died.Thanks to the acaricidal effect of TPP, a new treatment strategy using the KINPen09 for tick-infested pets is now available.

  9. Towards a biomimetism of abdominal healthy and aneurysmal arterial tissues.

    Science.gov (United States)

    Bailly, L; Geindreau, C; Orgéas, L; Deplano, V

    2012-06-01

    The aim of this work is to develop a new hyperelastic and anisotropic material mimicking histological and mechanical features of healthy and aneurysmal arterial tissues. The material is constituted by rhombic periodic lattices of hyperelastic fibres embedded into a soft elastomer membrane. To fit bi-axial experimental data obtained from the literature, with normal or pathologic human abdominal aortic tissues, the microstructure of the periodic lattices (fibre length, angle between fibres) together with the mechanical behaviour of the fibres (fibre tension-elongation curve) were optimised by using theoretical results arising from a multi-scale homogenisation process. It is shown that (i) a material constituted by only one periodic lattice of fibres is clearly not sufficient to describe all the experimental data set, (ii) a quantitative agreement between measurements and theoretical predictions is obtained by using a material with two fibre lattices, (iii) the optimised microstructures and mechanical properties of the fibrous lattices are strongly different for the abdominal healthy and aneurysmal arterial tissues, (iv) the anisotropic mechanical behaviour of the optimised material is described by only five parameters and (v) the optimal angles between fibres in the case of the healthy aorta are consistent with histological data. Several technical solutions of fibres can be considered as relevant candidates: this is illustrated in the particular cases of straight and wavy fibres. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Six Different Fat Tolerance Tests in Young, Healthy Subjects

    DEFF Research Database (Denmark)

    Rasmussen, Ole Winther; Lauszus, Finn Friis

    2016-01-01

    Background: exacerbated postprandial lipid responses are associated with an increaseed cardiovascular risk. Meals with different types of fat may effect postprandial responses differently. the aim og is tudy bwas to evaluate the postprandial lipemia in young healthy subjects after six oral fat...... tolerenctes (OFTT) with varying amoun of saturated fat. Methods: With six different types of fatin random order to tomatoes we measured postprandial lipemia, lipoprotein, glucose and insulin increments for eight hours in 14 young lean healthy students, seven of each gender. The area under the curve (AUC......) was dtermined for the postprandial values. Results: The meals with six types of butters had similar postprandial response even if the saturated fat content varied with 50%.Gender significantly affected the TG responses, as time to pesk was 90 minutes in women and 180 min in men. Postprandial AUC was higherwith...

  11. Benefits of healthy adipose tissue in the treatment of diabetes.

    Science.gov (United States)

    Gunawardana, Subhadra C

    2014-08-15

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin. Insulin deficiency is either absolute due to destruction or failure of pancreatic β cells, or relative due to decreased sensitivity of peripheral tissues to insulin. The primary lesion being related to insulin, treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin. These therapies have their own limitations and complications, some of which can be life-threatening. For example, exogenous insulin administration can lead to fatal hypoglycemic episodes; islet/pancreas transplantation requires life-long immunosuppressive therapy; and anti-diabetic drugs have dangerous side effects including edema, heart failure and lactic acidosis. Thus the need remains for better safer long term treatments for diabetes. The ultimate goal in treating diabetes is to re-establish glucose homeostasis, preferably through endogenously generated hormones. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism. While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties, which can complement and/or compensate for the function of insulin. Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin. Although specific adipokines may correct diabetes, administration of individual adipokines still carries risks similar to those of insulin monotherapy. Thus a

  12. Impaired Glucose Tolerance in Healthy Men Treated with St. John's Wort.

    Science.gov (United States)

    Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard; Nielsen, Lene Buch-Krogh; Højlund, Kurt; Brøsen, Kim

    2016-03-01

    The purpose of this study was to examine whether the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions: A: baseline; B: after 21 days of treatment with St. John's wort; and C: at least 6 weeks after the last capsule of St. John's wort was ingested. Plasma glucose, serum insulin and C-peptide levels were measured during an oral glucose tolerance test and used for estimation of area under the concentration-time curve (AUC) as well as indices of insulin sensitivity and insulin secretion. We found that treatment with St. John's wort increased total and incremental glucose AUC and 2-hr plasma glucose levels. Surprisingly, this effect was sustained and even further increased 6 weeks after the last capsule of St. John's wort was taken. No effect on indices of insulin sensitivity was seen, but indices of insulin secretion were reduced even after adjustment for insulin sensitivity. In conclusion, this study indicates that long-term treatment with St. John's wort may impair glucose tolerance by reducing insulin secretion in young, healthy men. The unregulated use of this over-the-counter drug might be a risk factor for impaired glucose tolerance and type 2 diabetes.

  13. Tolerance of natural baby skin-care products on healthy, full-term infants and toddlers

    OpenAIRE

    Coret CD; Suero MB; Tierney NK

    2014-01-01

    Catherine D Coret, Michael B Suero, Neena K Tierney Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, USA Purpose: To evaluate the tolerance of baby skin-care products with at least 95% naturally derived ingredients on infants and toddlers. Materials and methods: Healthy, full-term infants and toddlers aged 1–36 months were enrolled. In study 1, a lightly fragranced natural baby hair and body wash (n=30), a lightly fragranced natural baby shampoo (n=30), or a lightly...

  14. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers

    OpenAIRE

    Raut, Ashwinikumar A.; Rege, Nirmala N.; Tadvi, Firoz M.; Solanki, Punita V.; Kene, Kirti R.; Shirolkar, Sudatta G.; Shefali N Pandey; Vaidya, Rama A.; Ashok B Vaidya

    2012-01-01

    Ashwagandha (Withania somnifera) (WS), a “rasayana” drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two ...

  15. Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans.

    Science.gov (United States)

    Venables, Michelle C; Hulston, Carl J; Cox, Hannah R; Jeukendrup, Asker E

    2008-03-01

    Green tea consumption is reportedly associated with various health-promoting properties. For example, it has been shown to promote fat oxidation in humans at rest and to prevent obesity and improve insulin sensitivity in mice. We investigated the effects of acute ingestion of green tea extract (GTE) on glucose tolerance and fat oxidation during moderate-intensity exercise in humans. Two studies were performed, both with a counter-balanced crossover design. In study A, 12 healthy men performed a 30-min cycling exercise at 60% of maximal oxygen consumption (VO2max) before and after supplementation. In study B, 11 healthy men took an oral-glucose-tolerance test before and after supplementation. In the 24-h period before the experimental trials, participants ingested 3 capsules containing either GTE (total: 890 +/- 13 mg polyphenols and 366 +/- 5 mg EGCG) or a corn-flour placebo (total: 1729 +/- 22 mg). Average fat oxidation rates were 17% higher after ingestion of GTE than after ingestion of placebo (0.41 +/- 0.03 and 0.35 +/- 0.03 g/min, respectively; P fat oxidation to total energy expenditure was also significantly higher, by a similar percentage, after GTE supplementation. The insulin area under the curve decreased in both the GTE and placebo trials (3612 +/- 301 and 4280 +/- 309 microIU/dL . 120 min, respectively; P fat oxidation during moderate-intensity exercise and can improve insulin sensitivity and glucose tolerance in healthy young men.

  16. Expression of the thrombopoietin gene in tissues from healthy dogs.

    Science.gov (United States)

    Figueiredo, A S; Bulla, S C; Lunsford, K V; Bulla, C

    2013-01-01

    Thrombopoietin (THPO) is the major cytokine that regulates megakaryopoiesis and platelet production. Several human and murine studies have demonstrated that THPO is primarily synthesized in the liver, but the kidney, spleen and bone marrow are also sites of expression. The aim of this study was to determine THPO mRNA levels in a range of canine tissues by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Samples of bone marrow (n = 5), liver (n = 10), lung (n = 10), renal cortex (n = 10), renal medulla (n = 5) and spleen (n = 10) were obtained from 10 healthy, hound-cross dogs aged 6-8 months. The highest THPO mRNA levels were found in the liver, followed by the bone marrow, spleen, lung and kidney. There was a 13-fold difference in expression between liver and kidney. The bone marrow showed high levels of THPO mRNA in the absence of disease. The liver and bone marrow are likely to be the major sites of THPO production in the dog. Published by Elsevier Ltd.

  17. Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

    Science.gov (United States)

    Caddeo, Silvia; Boffito, Monica; Sartori, Susanna

    2017-01-01

    In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and

  18. Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

    Directory of Open Access Journals (Sweden)

    Silvia Caddeo

    2017-07-01

    Full Text Available In the tissue engineering (TE paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart

  19. Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability.

    Science.gov (United States)

    Glue, Paul; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, Cheung-Tak; Friedhoff, Lawrence

    2015-02-01

    Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers.

  20. Tolerability and pharmacokinetics of ebrotidine in healthy subjects given single and repeated oral doses.

    Science.gov (United States)

    Farré, M; Roset, P N; Badenas, J M; Ugena, B; Márquez, M; Albet, C; Herrero, E; Ortiz, J A

    1997-04-01

    The tolerability and safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) and its basic pharmacokinetic parameters were determined after its oral administration to healthy volunteers. Sixteen subjects were selected to participate in two different studies: an increasing single dose study to determine the maximal tolerated dose (from 25 to 1600 mg), and a multiple dose study (stepped doses from 400 to 1600 mg daily for 12 days). The results of the studies showed that ebrotidine has a good tolerability. Vital signs and laboratory tests were not influenced by the study treatment. No clinically relevant adverse effects were reported during the investigation. Ebrotidine reached peak plasma concentrations 2-3 h after oral administration. Its elimination half-life ranged from 9 to 14 h. In conclusion, ebrotidine was well tolerated after administration of oral single doses of up to 1600 mg, and after repeated administration of up to 800 mg/12 h for 12 days.

  1. Exercise increases pressure pain tolerance but not pressure and heat pain thresholds in healthy young men

    DEFF Research Database (Denmark)

    Vaegter, H. B.; Bement, M. Hoeger; Madsen, A. B.

    2017-01-01

    : On three different days, 20 healthy young men performed two submaximal isometric knee extensions (30% maximal voluntary contraction in 3 min) and a control condition (quiet rest). Before and immediately after exercise and rest, the sensitivity to heat pain and pressure pain was assessed in randomized......BACKGROUND: Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. METHODS...... and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. RESULTS: Cuff pressure pain tolerance...

  2. Validity and interobserver agreement of lower extremity local tissue water measurements in healthy women using tissue dielectric constant

    DEFF Research Database (Denmark)

    Jensen, Mads R; Birkballe, Susanne; Nørregaard, Susan

    2012-01-01

    Tissue dielectric constant (TDC) measurement may become an important tool in the clinical evaluation of chronic lower extremity swelling in women; however, several factors are known to influence TDC measurements, and comparative data on healthy lower extremities are few....

  3. Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers

    Institute of Scientific and Technical Information of China (English)

    Pei-hong SUN; Xia ZHAO; Ying ZHOU; Yan LIANG; Hui-lin ZHANG; Yi-min CUI; Ji-ning TAO

    2011-01-01

    To investigate the safety,tolerability and pharmacokinetics of intravenous hemoporfin,a novel photosensitive drug for the treatment of port-wine stain (PWS),in healthy Chinese volunteers following single-dose administration.Methods:Thirty-six healthy Chinese subjects were enrolled.The subjects were administered hemoporfin (2.5,5,7.5 or 10 mg/kg) via single-dose intravenous infusion.Pharmacokinetics of the drug were studied in the groups with doses of 2.5,5 and 7.5 mg/kg,and tolerability was studied in all the 4 groups.Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters,and pharmacokinetics were assessed by determining hemoporfin content with a validated high-performance liquid chromatography with fluorescence detection (HPLC/FLD) method.Results:Mild and transient adverse events occurred in the trial (n=1O),but none were serious,and no subjects were withdrawn from the trial.The gastrointestinal tract adverse events,such as nausea,stomach upset,abdominal pain and vomiting,were observed in the groups with doses of 7.5 and 10 mg/kg.Increased alanine aminotransferase (ALT) concentration was found in 3 subjects,and increased alkaline phosphatase (ALP) concentration in one subject.The half-life of hemoporfin for doses of 2.5,5,and 7.5 mg/kg was 1.26 h,1.31 h,and 1.70 h,respectively.Cmax and AUC increased with dose for intravenous single-dose administration of hemoporfin in the 2.5,5,and 7.5 mg/kg groups.Urinary excretion of hemoporfin within 12 h was less than 0.2%.Conclusion:Hemoporfin is safe and well-tolerated in healthy Chinese volunteers at a single intravenous dose of up to 10 mg/kg.It was rapidly cleared from the blood and had a short half-life,which insures a short light-avoidance period.

  4. Clinical pharmacokinetics and tolerability of dotarizine in healthy subjects after single and multiple oral administration.

    Science.gov (United States)

    Farré, M; Roset, P N; Llorente, M; Márquez, M; Albet, C; Pérez, J A; Herrero, E; Ortíz, J A

    1997-06-01

    Dotarizine is a new diphenylmethylpiperazine derivative with Ca2+ channel blocking properties and inhibitory effects on 5-HT2A and 5-HT2C receptors. Previous pilot studies in healthy volunteers demonstrated a good tolerability after single and multiple dosing. Dotarizine appeared to be rapidly and extensively metabolized to an active compound (FI-6020). We aimed to study the physiologic, subjective and psychomotor acute effects of oral dotarizine after single dose administration, to evaluate the tolerability and safety after multiple dosing over 2 weeks, and to study the pharmacokinetic parameters and linearity after single and multiple administration. Two different studies were carried out in 2 groups of 8 healthy male volunteers. Oral single doses of dotarizine 50, 100 and 200 mg were administered in a randomized, double-blind, crossover, placebo-controlled trial. Oral doses of 50 mg twice daily were administered in an open trial over 14 days. Drug effect assessments included vital signs, collection of adverse events, ECG and blood and urine safety evaluations, subjective effects, psychomotor performance tasks and blood sampling. Dotarizine and its metabolite were determined by gas chromatography with N-P detector. The results showed a good tolerability of dotarizine after single oral doses as well as multiple oral doses over 14 days. No clinically relevant adverse events were reported during the study. The highest single dose (200 mg) produced a slight increase in sedation-related symptoms as well as a slight impairment in psychomotor performance tasks. Dotarizine and its major metabolite proved linear kinetics at single doses. The administration of oral doses of dotarizine 50 mg b.i.d. reached the steady state after the 7th day of treatment. The pharmacokinetic parameters remained similar from day 7 to day 14. The terminal elimination half-life of dotarizine and its metabolite appeared to be between 7 and 12 h.

  5. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Ashwinikumar A Raut

    2012-01-01

    Full Text Available Ashwagandha (Withania somnifera (WS, a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30 were enrolled. After baseline investigations, they received WS capsules (Rx (aqueous extract, 8:1 daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day x10 days, 1 000 mg/day x 10 days, 1 250 mg/day x 10 days. Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar′s test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  6. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers.

    Science.gov (United States)

    Raut, Ashwinikumar A; Rege, Nirmala N; Tadvi, Firoz M; Solanki, Punita V; Kene, Kirti R; Shirolkar, Sudatta G; Pandey, Shefali N; Vaidya, Rama A; Vaidya, Ashok B

    2012-07-01

    Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  7. Tolerability of intramuscular and intradermal delivery by CELLECTRA® adaptive constant current electroporation device in healthy volunteers

    Science.gov (United States)

    Diehl, Malissa C; Lee, Jessica C; Daniels, Stephen E; Tebas, Pablo; Khan, Amir S; Giffear, Mary; Sardesai, Niranjan Y; Bagarazzi, Mark L

    2013-01-01

    DNA vaccines are being developed as a potentially safe and effective immunization platform. However, translation of DNA vaccines into a clinical setting has produced results that have fallen short of those generated in a preclinical setting. Various strategies are being developed to address this lack of potency, including improvements in delivery methods. Electroporation (EP) creates transient increases in cell membrane permeability, thus enhancing DNA uptake and leading to a more robust immune response. Here, we report on the safety and tolerability of delivering sterile saline via intramuscular (IM) or intradermal (ID) injection followed by in vivo electroporation using the CELLECTRA® adaptive constant current device in healthy adults from two open-label studies. Pain, as assessed by VAS, was highest immediately after EP but diminishes by about 50% within 5 min. Mean VAS scores appear to correlate with the amount of energy delivered and depth of needle insertion, especially for intramuscular EP. Mean scores did not exceed 7 out of 10 or 3 out of 10 for IM and ID EP, respectively. The majority of adverse events included mild to moderate injection site reactions that resolved within one day. No deaths or serious adverse events were reported during the course of either study. Overall, injection followed by EP with the CELLECTRA® device was well-tolerated and no significant safety concerns were identified. These studies support the further development of electroporation as a vaccine delivery method to enhance immunogenicity, particularly for diseases in which traditional vaccination approaches are ineffective. PMID:24051434

  8. Self directed home based electrical muscle stimulation training improves exercise tolerance and strength in healthy elderly.

    Science.gov (United States)

    Caulfield, Brian; Prendergast, Ann; Rainsford, Gary; Minogue, Conor

    2013-01-01

    Advancing age is associated with a gradual decline in muscle strength, exercise tolerance and subsequent capacity for activities of daily living. It is important that we develop effective strategies to halt this process of gradual decline in order to enhance functional ability and capacity for independent living. To achieve this, we must overcome the challenge of sustaining ongoing engagement in physical exercise programmes in the sedentary elderly population, particularly those who experience barriers to exercise participation. Recent developments in electrical muscle stimulation technology could provide a potential solution. In this pilot case-control study we investigated the effects of a self-directed home based programme of electrical muscle stimulation training on muscle strength and exercise tolerance in a group of 16 healthy elderly volunteers (10f, 6m). Study participants completed 30 separate 1-hour electrical muscle stimulation sessions at home over a 6-week period. We observed significant improvements in quadriceps muscle strength and 6-minute walk distance, suggesting that this form of electrical muscle stimulation training has promise as an exercise modality in the elderly population.

  9. Identification of novel adipokines in the joint. Differential expression in healthy and osteoarthritis tissues.

    Directory of Open Access Journals (Sweden)

    Javier Conde

    Full Text Available Emerging data suggest that several metabolic factors, released mainly by white adipose tissue (WAT and joint tissues, and collectively named adipokines, might have a role in the pathophysiology of OA. Recently, novel adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT. The main goal of this study was to analyse the expression of these novel adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the expression of these molecules in healthy and OA tissues.Synovial tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients (age 52-85; mean BMI 28.9 who underwent total knee replacement surgery. Healthy synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee patients (age 23-53; mean BMI 23.5. mRNA and protein expression were determined by qRT-PCR and western blot analysis respectively.All the novel adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2 and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also observed an increased expression of WISP2 in OA infrapatellar fat pad in comparison to healthy controls.In this study we demonstrated for the first time the expression of four novel adipokines in different joint tissues and how these molecules are differentially expressed in healthy and OA joint tissues.

  10. Assessment of pharmacokinetics and tolerability of intranasal diazepam relative to rectal gel in healthy adults.

    Science.gov (United States)

    Henney, Herbert R; Sperling, Michael R; Rabinowicz, Adrian L; Bream, Gary; Carrazana, Enrique J

    2014-09-01

    Diazepam rectal gel (RG) is currently the only approved rescue therapy for outpatient management of seizure clusters in the United States. There is an unmet medical need for an alternative rescue therapy for seizure clusters that is effective, and more convenient to administer with a socially acceptable method of delivery. An intranasal diazepam formulation has been developed, and this study evaluates the tolerability and bioavailability of diazepam nasal spray (NS) relative to an equivalent dose of diazepam-RG in healthy adults. Twenty-four healthy adults were enrolled in a phase 1, open-label, 3-period crossover study. Plasma diazepam and metabolite concentrations were measured by serial sampling. Dose proportionality for 5- and 20-mg intranasal doses and the bioavailability of 20mg diazepam-NS relative to 20mg diazepam-RG were assessed by maximum plasma concentration (Cmax) and systemic exposure parameters (AUC0-∞ and AUC0-24). The mean Cmax values for 20mg diazepam-NS and 20mg diazepam-RG were 378 ± 106 and 328 ± 152 ng/mL, achieved at 1.0 and 1.5h, respectively. Subjects administered intranasal and rectal gel formulations experienced nasal and rectal leakage, respectively. Diazepam absorption following intranasal administration was consistent but 3 subjects with diazepam-RG had low plasma drug levels at the earliest assessment of 5 min, due to poor retention, and were excluded from analysis. Excluding them, the treatment ratios (20mg diazepam-NS:20mg diazepam-RG) and 90% confidence intervals for diazepam Cmax and AUC0-24 were 0.98 (0.85-1.14) and 0.89 (0.80-0.98), respectively, suggesting that the bioavailability was comparable between the two formulations. Dose proportionality was observed between the lowest and highest dose-strengths of intranasal formulation. Both intranasal and rectal treatments were well tolerated with mild to moderate adverse events. Results suggest that a single-dose of 20mg diazepam-NS is tolerable and comparable in bioavailability

  11. Effect of probenecid on pharmacokinetics and tolerability of olmesartan in healthy chinese volunteers.

    Science.gov (United States)

    Li, Kun-Yan; Qiu, Yu; Jiang, Yun; Luo, Chen-Hui; Lin, Xiao-Ping; Wang, Jing; Yang, Nong

    2014-12-01

    Olmesartan is an angiotensin II receptor antagonist and is effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricemic agent for the treatment of hyperuricemia and gout. The goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers. In a randomized, open-label, 2-way crossover study, 12 volunteers received 2 oral treatments (olmesartan alone or olmesartan plus probenecid) separated by 4 days. Blood samples were obtained for a 48-hour pharmacokinetic evaluation after drug administration. Tolerability was assessed by monitoring vital signs and laboratory tests before and after administration of the study drug. Pharmacokinetic parameters were evaluated in 6 male and 6 female healthy volunteers (mean age, 22 [range, 20-25] years]; weight, 56.0 [range, 51.0-60.0] kg). Probenecid coadministration increased olmesartan Css-av, AUC0→∞, and AUC0-48 by 40%, 50%, and 50%, respectively (P = 0.018, 0.000, 0.000, respectively), but there was no statistical significance for Tmax, t1/2, Css-max, and Css-min between olmesartan plus probenecid and olmesartan alone (P = 0.697, 0.053, 0.521, and 0.734, respectively). No serious adverse event (AE) was reported during the study. The proportion of volunteers with AEs in the olmesartan plus probenecid period (5 of 12 [42%]) was higher than that in the olmesartan-alone period (1 of 12 [8%]). All of the AEs during the olmesartan plus probenecid period were abnormal routine urine test results. The AE in olmesartan-alone period was dizziness. All AEs were classified as mild and considered to be at least possibly related to treatment. All volunteers recovered from the AEs by 2 weeks after the end of the study. Probenecid increases the exposure speed of olmesartan by increasing the AUC0-48, AUC0→∞, and Css-av. The combined treatment of olmesartan medoxomil with probenecid

  12. Catalase activity in healthy and inflamed pulp tissues of permanent ...

    African Journals Online (AJOL)

    2015-11-02

    Nov 2, 2015 ... one pulp tissue specimens. The specimens were collected during endodontic treatment or by longitudinally grooving and .... pain caused by thermal and electrical tests, with clinically ... to release H2O2 into the extracellular environment.[13,14] ... included. Previously restored and caries teeth were also not.

  13. A new topical panthenol-containing emollient: skin-moisturizing effect following single and prolonged usage in healthy adults, and tolerability in healthy infants.

    Science.gov (United States)

    Stettler, Hans; Kurka, Peter; Wagner, Christine; Sznurkowska, Katarzyna; Czernicka, Olga; Böhling, Arne; Bielfeldt, Stephan; Wilhelm, Klaus-Peter; Lenz, Holger

    2017-05-01

    Two studies were conducted with a new topical panthenol-containing emollient (NTP-CE) to investigate the skin-moisturizing effect in healthy adults and tolerability in healthy infants. In Study 1 (N = 44), a single skin application of NTP-CE was performed followed by a 4-week twice-daily application. Skin hydration and stratum corneum (SC) water content change (using Raman spectroscopy) were measured. In the 4-week Study 2 (N = 65, aged 3-25 months), NTP-CE tolerability was assessed using a 5-point scoring system; skin hydration was determined in a subset (N = 21). In Study 1, mean AUC0 - 24 h for skin capacitance change from baseline was 302.03 i.u. with NTP-CE and -15.90 i.u. in control areas (p water content within the upper SC part was reduced (-45.10 vs. -13.39 g/cm(2), p = .013) and the water gradient increased (0.51 vs. 0.11 g/cm(4), p = .036), indicating relocation of water into deeper layers. In Study 2, there was no statistically significant change from baseline in mean cutaneous tolerability scores. At days 7, 14, and 28, skin hydration had increased by 42%, 54%, and 49%, respectively (all p usage is associated with sustained and deep skin moisturization. NTP-CE is well tolerated by healthy infants.

  14. Simplified methods for screening cowpea cultivars for manganese leaf-tissue tolerance. [Vigna unguiculata

    Energy Technology Data Exchange (ETDEWEB)

    Wissemeier, A.H.; Horst, W.J. (Univ. of Hannover (West Germany))

    In cowpea (Vigna unguiculata (L.) Walp.) dark brown speckles on old leaves are typical symptoms of Mn toxicity and indicate Mn sensitivity of leaf tissue. Induction and subsequent quantification of brown Mn speckles in leaf tissues were used to screen cowpea cultivars for Mn leaf-tissue tolerance using three different techniques: (i) leaf cuttings cultured for 22 days in solution culture with 20 {mu}M MnSO{sub 4}, (ii) leaf rings mounted on leaves of intact plants and filled with 500 {mu}M MnSO{sub 4} for 5 days, and (iii) leaf disks floated for 3 days on 500 {mu}M MnSO{sub 4}. Density of brown speckles differed considerably among the six cultivars tested, and was not related to the Mn concentrations of the leaf tissues. There were close relationships between genotypic Mn-toxicity symptom expression and depression of dry matter production of the cultivars at high Mn supply in a long-term sand culture experiment. The floating leaf-disk method is particularly suited for screening large numbers of cowpea cultivars for Mn leaf-tissue tolerance because it requires only 3 days. The ranking of the cultivars for Mn tolerance was highly correlated to Mn tolerance of intact plants.

  15. Tolerance of skin care regimen in healthy, full-term neonates.

    Science.gov (United States)

    Iarkowski, Laura Ellen; Tierney, Neena K; Horowitz, Paul

    2013-01-01

    To assess the tolerance of a baby cleanser and lotion (both lightly fragranced) on healthy, full-term neonates. Twenty-six infant-mother pairs were enrolled in a 6-week, nonrandomized, controlled-use study that took place in the routine setting of a pediatric clinic and mothers' homes. During study weeks 1 to 6, neonates were bathed by their mother with water and a test cleanser (JOHNSON'S® HEAD-TO-TOE® Baby Wash). During study weeks 1 to 3, mothers also applied test lotion (JOHNSON'S® Baby Lotion) to the babies' skin immediately after bathing and one to three times/day on bathing and non-bathing days. During study weeks 4 to 6, no lotion was applied. At baseline and weeks 3 and 6, the infants' pediatrician or mother or both performed visual skin assessments. Twenty-three infant-mother pairs completed the study. The mean age of neonates at enrolment was 17.4 days (range, 13-28 days). Pediatrician observations found no clinical signs of irritation, erythema, or dryness with any significant difference in scores of these parameters compared with baseline throughout the study. Assessment of skin softness, smoothness, dryness, and overall skin condition was very good at baseline and remained so with minimal changes throughout the study. Mothers reported improvements versus baseline (P ≤ 0.05) in overall skin appearance, moisturization, softness, and smoothness on the arms and legs at weeks 3 and 6. A total of four (15.4%) subjects experienced adverse events. For three of the subjects, the investigator suspected that the adverse events were unrelated to either of the test products. In one participant, the cause of the adverse event could not be determined. The use of a lightly fragranced nonstinging baby cleanser, with or without a lightly fragranced baby lotion, was well tolerated by newborns and resulted in observable skin benefits per the pediatricians' and mothers' assessment.

  16. Alternative Promoter Usage in Healthy and Inflamed Tissue

    DEFF Research Database (Denmark)

    Lilje, Berit

    and cell-lines covering the entire human body. This provides a unique dataset to study gene expression, with promoter level precision. Here we use this large collection of data to study alternative transcription start site usage throughout the human body. We find that many alternative transcription start...... the full-length version. Our results suggest alternative transcription start site usage currently is underappreciated, since these start sites often show high expression compared to canonical start sites. We further show that the usage of alternative transcription start sites can both be tissue specific......, as well as specific to certain differentiation states. By analysing CAGE data from two different inflammatory responses we also find that alternative transcription start site usage is an intrinsic part of the inflammatory response. CAGE was used to map transcription start sites in Caco-2 cells stimulated...

  17. Tolerance of natural baby skin-care products on healthy, full-term infants and toddlers

    Directory of Open Access Journals (Sweden)

    Coret CD

    2014-02-01

    Full Text Available Catherine D Coret, Michael B Suero, Neena K Tierney Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, USA Purpose: To evaluate the tolerance of baby skin-care products with at least 95% naturally derived ingredients on infants and toddlers. Materials and methods: Healthy, full-term infants and toddlers aged 1–36 months were enrolled. In study 1, a lightly fragranced natural baby hair and body wash (n=30, a lightly fragranced natural baby shampoo (n=30, or a lightly fragranced natural baby lotion (n=32 were assessed over 2 weeks. In study 2, a lightly fragranced natural baby hair and body wash and a lightly fragranced natural baby lotion (n=33 were assessed as a regimen over 4 weeks. The wash and shampoo were used three or more times per week, but not more than once daily. Lotions were applied in the morning or after a bath. Clinicians assessed the arms, legs, torso, or scalp for erythema, dryness, peeling/flakiness (study 1 only, tactile roughness, edema (study 1 only, rash/irritation (study 2 only, and overall skin condition (study 2 only at baseline, week 1, and weeks 2 or 4. Parents completed skin assessment questionnaires. In study 2, stratum corneum hydration was measured. Subjects were monitored for adverse events. Results: No significant changes in clinical grading scores were observed, indicating that all products were well tolerated. By the end of each study, >90% of parents/caregivers believed each product was mild and gentle. In study 2, improvement in stratum corneum hydration was observed (+37% at week 1 and +48% at week 4, P<0.05 for both. In study 1, one baby experienced mild erythema on the neck and scalp after using the shampoo (possibly related to treatment. In study 2, there were no product-related adverse events. Conclusion: The natural baby skin-care products were well tolerated by infants and toddlers when used alone or as part of a skin-care regimen. Keywords: bath, cleanser, natural, infant, lotion, shampoo

  18. Tolerability, pharmacokinetics, and neuroendocrine effects of PRX-00023, a novel 5-HT1A agonist, in healthy subjects.

    Science.gov (United States)

    Iyer, Ganesh R; Reinhard, John F; Oshana, Scott; Kauffman, Michael; Donahue, Stephen

    2007-07-01

    PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for treatment of affective disorders. The objectives of the initial clinical phase I studies (a single ascending dose study and multiple dose-ascending and high-dose titration studies) were to measure the pharmacokinetics, pharmacodynamic (neuroendocrine) effects, and tolerability of PRX-00023 in healthy subjects. The studies evaluated 10-mg to 150-mg doses of PRX-00023 in up to 112 healthy male and female subjects aged 18 to 54 years. Single and multiple oral doses of PRX-00023 were found to be safe and well tolerated in healthy subjects. PRX-00023 was absorbed relatively rapidly, with a tmax of 0.5 to 2 hours, and eliminated with a half-life of approximately 12 hours. PRX-00023 treatment transiently increased blood prolactin levels 2 to 3 hours after administration, consistent with its mechanism as a 5-HT1A agonist.

  19. A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.

    Science.gov (United States)

    Agarwal, Suresh K; Kriel, Robert L; Cloyd, James C; Coles, Lisa D; Scherkenbach, Lisa A; Tobin, Michael H; Krach, Linda E

    2015-01-01

    Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures.

  20. Tolerance of skin care regimen in healthy, full-term neonates

    Directory of Open Access Journals (Sweden)

    Iarkowski LE

    2013-05-01

    Full Text Available Laura Ellen Iarkowski,1 Neena K Tierney,1 Paul Horowitz21Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, USA; 2Discovery Pediatrics, Valencia, CA, USAPurpose: To assess the tolerance of a baby cleanser and lotion (both lightly fragranced on healthy, full-term neonates.Materials and methods: Twenty-six infant–mother pairs were enrolled in a 6-week, nonrandomized, controlled-use study that took place in the routine setting of a pediatric clinic and mothers’ homes. During study weeks 1 to 6, neonates were bathed by their mother with water and a test cleanser (JOHNSON'S® HEAD-TO-TOE® Baby Wash. During study weeks 1 to 3, mothers also applied test lotion (JOHNSON'S® Baby Lotion to the babies’ skin immediately after bathing and one to three times/day on bathing and non-bathing days. During study weeks 4 to 6, no lotion was applied. At baseline and weeks 3 and 6, the infants’ pediatrician or mother or both performed visual skin assessments.Results: Twenty-three infant–mother pairs completed the study. The mean age of neonates at enrolment was 17.4 days (range, 13–28 days. Pediatrician observations found no clinical signs of irritation, erythema, or dryness with any significant difference in scores of these parameters compared with baseline throughout the study. Assessment of skin softness, smoothness, dryness, and overall skin condition was very good at baseline and remained so with minimal changes throughout the study. Mothers reported improvements versus baseline (P ≤ 0.05 in overall skin appearance, moisturization, softness, and smoothness on the arms and legs at weeks 3 and 6. A total of four (15.4% subjects experienced adverse events. For three of the subjects, the investigator suspected that the adverse events were unrelated to either of the test products. In one participant, the cause of the adverse event could not be determined.Conclusion: The use of a lightly fragranced nonstinging baby cleanser, with or without a

  1. Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers.

    Science.gov (United States)

    Allen, A; Bygate, E; Vousden, M; Oliver, S; Johnson, M; Ward, C; Cheon, A; Choo, Y S; Kim, I

    2001-02-01

    Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean +/- standard deviation values of AUC(0-tau) on day 7 were 4.92 +/- 1.08, 9.06 +/- 2.20, 12.2 +/- 3.69, and 20.1 +/- 3.67 microg x h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate

  2. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance.

    Science.gov (United States)

    Soroosh, Pejman; Doherty, Taylor A; Duan, Wei; Mehta, Amit Kumar; Choi, Heonsik; Adams, Yan Fei; Mikulski, Zbigniew; Khorram, Naseem; Rosenthal, Peter; Broide, David H; Croft, Michael

    2013-04-01

    Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3(+) iTreg cells is unclear. Here, we show that lung-resident tissue MØs coexpress TGF-β and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3(+) Treg cells. Treg cell induction in this model depended on both TGF-β and retinoic acid. Transfer of the antigen-pulsed tissue MØs into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue MØs to allergens suppressed their ability to generate iTreg cells coincident with blocking airway tolerance. Suppression of Treg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue MØs have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma.

  3. Nrf2 as a master regulator of tissue damage control and disease tolerance to infection.

    Science.gov (United States)

    Soares, Miguel P; Ribeiro, Ana M

    2015-08-01

    Damage control refers to those actions made towards minimizing damage or loss. Depending on the context, these can range from emergency procedures dealing with the sinking of a ship or to a surgery dealing with severe trauma or even to an imaginary company in Marvel comics, which repairs damaged property arising from conflicts between super heroes and villains. In the context of host microbe interactions, tissue damage control refers to an adaptive response that limits the extent of tissue damage associated with infection. Tissue damage control can limit the severity of infectious diseases without interfering with pathogen burden, conferring disease tolerance to infection. This contrasts with immune-driven resistance mechanisms, which although essential to protect the host from infection, can impose tissue damage to host parenchyma tissues. This damaging effect is countered by stress responses that confer tissue damage control and disease tolerance to infection. Here we discuss how the stress response regulated by the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) acts in such a manner. © 2015 Authors.

  4. Nrf2 as a master regulator of tissue damage control and disease tolerance to infection

    Science.gov (United States)

    Soares, Miguel P.; Ribeiro, Ana M.

    2015-01-01

    Damage control refers to those actions made towards minimizing damage or loss. Depending on the context, these can range from emergency procedures dealing with the sinking of a ship or to a surgery dealing with severe trauma or even to an imaginary company in Marvel comics, which repairs damaged property arising from conflicts between super heroes and villains. In the context of host microbe interactions, tissue damage control refers to an adaptive response that limits the extent of tissue damage associated with infection. Tissue damage control can limit the severity of infectious diseases without interfering with pathogen burden, conferring disease tolerance to infection. This contrasts with immune-driven resistance mechanisms, which although essential to protect the host from infection, can impose tissue damage to host parenchyma tissues. This damaging effect is countered by stress responses that confer tissue damage control and disease tolerance to infection. Here we discuss how the stress response regulated by the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) acts in such a manner. PMID:26551709

  5. Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers.

    Science.gov (United States)

    Allen, A; Bygate, E; Oliver, S; Johnson, M; Ward, C; Cheon, A J; Choo, Y S; Kim, I C

    2000-06-01

    Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.

  6. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  7. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  8. Chemometric methods for studying the relationships between trace elements in laryngeal cancer and healthy tissues.

    Science.gov (United States)

    Dobrowolski, R; Klatka, J; Brodnjak-Voncina, D; Trojanowska, A; Myśliwiec, D; Ostrowski, J; Remer, M

    2014-06-01

    A quick and reliable method for the evaluation and classification of two types of tissues is presented. Several chemometric methods were applied to evaluate multivariate data of the tissue samples with respect to the content of trace elements. The content of Pb, Al, Zn, Cd, Cu, Ni and Co was determined in samples of healthy and cancerous tissue obtained from 26 patients. Determination was done at milligram/kilogram level with inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic absorption spectroscopy (AAS) techniques. Contents of trace metals in studied tissues are not normally distributed; however, normal distribution was confirmed for log values. There is a statistically significant difference in the content of Zn, Cd, Cu and Al (pcontents of trace elements for studied tissues was positive; the highest was found between Zn and Cu. A chemometric methodology seems to be a promising tool for classifications of the tissue samples.

  9. Liver transplantation in the mouse: Insights into liver immunobiology, tissue injury, and allograft tolerance.

    Science.gov (United States)

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A; Thomson, Angus W

    2016-04-01

    The surgically demanding mouse orthotopic liver transplant model was first described in 1991. It has proved to be a powerful research tool for the investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction, and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, because the mouse genome is well characterized and there is much greater availability of both genetically modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice have provided valuable mechanistic insights into the immunobiology and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in the regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/immune-mediated events in the hepatic environment and systemically. In conclusion, orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology, and allograft tolerance that may result in therapeutic innovation in the liver and in the treatment of other diseases.

  10. Localization of Staphylococcus aureus in tissue from the nasal vestibule in healthy carriers.

    Science.gov (United States)

    Hanssen, Anne-Merethe; Kindlund, Bert; Stenklev, Niels Christian; Furberg, Anne-Sofie; Fismen, Silje; Olsen, Renate Slind; Johannessen, Mona; Sollid, Johanna Ulrica Ericson

    2017-04-05

    Colonization of the body is an important step in Staphylococcus aureus infection. S. aureus colonizes skin and mucous membranes in humans and several animal species. One important ecological niche of S. aureus is the anterior nares. More than 60% of the S. aureus in the nose are found in vestibulum nasi. Our aim was to describe the localization of S. aureus in nasal tissue from healthy carriers. Punch skin biopsies were taken from vestibulum nasi from healthy volunteers (S. aureus carriers and non-/intermittent carriers, n = 39) attending the population-based Tromsø 6 study. The tissue samples were processed as frozen sections before immunostaining with a specific S. aureus antibody, and finally evaluated by a confocal laser-scanning microscope. Our results suggest that S. aureus colonize both the upper and lower layers of the epidermis within the nasal epithelium of healthy individuals. The number of S. aureus in epidermis was surprisingly low. Intracellular localization of S. aureus in nasal tissue from healthy individuals was also detected. Knowledge of the exact localization of S. aureus in nasal tissue is important for the understanding of the host responses against S. aureus. Our results may have consequences for the eradication strategy of S. aureus in carriers, and further work can provide us with tools for targeted prevention of S. aureus colonisation and infection.

  11. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men

    DEFF Research Database (Denmark)

    Asmar, Ali; Asmar, Meena; Simonsen, Lene

    2017-01-01

    In healthy subjects, we recently demonstrated that during acute administration of GLP-1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP-1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and....../or splanchnic tissues. Nine healthy men were examined twice in random order during a 2-hour infusion of either GLP-1 (1.5 pmol kg(-1) min(-1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra-arterial blood pressure. Subcutaneous, abdominal adipose...... and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP-1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP-1 increases cardiac...

  12. Neutrophil elastase causes tissue damage that decreases host tolerance to lung infection with burkholderia species.

    Directory of Open Access Journals (Sweden)

    Manoranjan Sahoo

    2014-08-01

    Full Text Available Two distinct defense strategies can protect the host from infection: resistance is the ability to destroy the infectious agent, and tolerance is the ability to withstand infection by minimizing the negative impact it has on the host's health without directly affecting pathogen burden. Burkholderia pseudomallei is a Gram-negative bacterium that infects macrophages and causes melioidosis. We have recently shown that inflammasome-triggered pyroptosis and IL-18 are equally important for resistance to B. pseudomallei, whereas IL-1β is deleterious. Here we show that the detrimental role of IL-1β during infection with B. pseudomallei (and closely related B. thailandensis is due to excessive recruitment of neutrophils to the lung and consequent tissue damage. Mice deficient in the potentially damaging enzyme neutrophil elastase were less susceptible than the wild type C57BL/6J mice to infection, although the bacterial burdens in organs and the extent of inflammation were comparable between C57BL/6J and elastase-deficient mice. In contrast, lung tissue damage and vascular leakage were drastically reduced in elastase-deficient mice compared to controls. Bradykinin levels were higher in C57BL/6 than in elastase-deficient mice; administration of a bradykinin antagonist protected mice from infection, suggesting that increased vascular permeability mediated by bradykinin is one of the mechanisms through which elastase decreases host tolerance to melioidosis. Collectively, these results demonstrate that absence of neutrophil elastase increases host tolerance, rather than resistance, to infection by minimizing host tissue damage.

  13. Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

    Science.gov (United States)

    Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-02-01

    Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

  14. A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

    Science.gov (United States)

    Sood, Sanjana; Gallagher, Iain J; Lunnon, Katie; Rullman, Eric; Keohane, Aoife; Crossland, Hannah; Phillips, Bethan E; Cederholm, Tommy; Jensen, Thomas; van Loon, Luc J C; Lannfelt, Lars; Kraus, William E; Atherton, Philip J; Howard, Robert; Gustafsson, Thomas; Hodges, Angela; Timmons, James A

    2015-09-07

    Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

  15. A simple optical fibre probe for differentiation between healthy and tumorous tissue

    Science.gov (United States)

    Schartner, Erik P.; Henderson, Matthew R.; Purdey, Malcolm; Monro, Tanya M.; Gill, P. Grantley; Callen, David F.

    2016-11-01

    Incomplete removal of malignant tumours continues to be a significant issue in cancer surgery. It increases the risk of local recurrence and impaired survival, and results in the need for additional surgery with associated attendant costs and morbidity. While pathological methods exist to determine tissue type during surgery, these methods can compromise post-operative pathology, have a lag of minutes to hours before the surgeon receives the results of the tissue analysis and are restricted to excised tissue. In this work we report the development of an optical fibre probe which could find use as an aid for margin detection during surgery. A fluorophore doped polymer coating is deposited on the tip of an optical fibre, which can then be used to record the pH by monitoring the emission spectra from the embedded indicator. The pH values of unknown tissue are measured and compared to healthy tissue, allowing for discrimination between healthy and cancerous tissue. The probe developed here shows strong potential for use during surgery, as the probe design can be readily adapted to a low-cost portable configuration which could find use in the operating theatre. Use of this probe in surgery either on excised or in-vivo tissue has the potential to improve success rates for complete removal of cancers.

  16. Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Moeko Noguchi-Shinohara

    Full Text Available The aim of this study was to evaluate the safety, tolerability and pharmacokinetics of single dose of Melissa officinalis extract which contained rosmarinic acid, including food-effects in healthy individuals. A total of eleven healthy individuals were randomly assigned to treatment arms in the two studies [Study 1 (fasted state and Study 2 (fed state]. Rosmarinic acid in serum was measured by a coulometric detection method using High-Performance Liquid Chromatography electrochemical detector. The serum concentration of total rosmarinic acid peaked at 1 hour after administration of Melissa officinalis extract containing 500mg rosmarinic acid in fasted state, with a maximum serum concentration 162.20 nmol/ L. The area under the curve for intact rosmarinic acid was calculated from the serum concentration-time profile to be 832.13 nmol • hour/ L. Food intake increases area under the curve and delayed time at which the maximum serum concentration. Rosmarinic acid supplementation did not affect liver, kidney, or blood cell function parameters. No adverse event was reported by any of the participants due to the study treatment. Single dose of Melissa officinalis extract containing 500 mg rosmarinic acid appears to be safe and tolerable in healthy individuals. Food intake increased the exposure of rosmarinic acid and delayed absorption of rosmarinic acid in healthy individuals.

  17. Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial.

    Science.gov (United States)

    Noguchi-Shinohara, Moeko; Ono, Kenjiro; Hamaguchi, Tsuyoshi; Iwasa, Kazuo; Nagai, Toshitada; Kobayashi, Shoko; Nakamura, Hiroyuki; Yamada, Masahito

    2015-01-01

    The aim of this study was to evaluate the safety, tolerability and pharmacokinetics of single dose of Melissa officinalis extract which contained rosmarinic acid, including food-effects in healthy individuals. A total of eleven healthy individuals were randomly assigned to treatment arms in the two studies [Study 1 (fasted state) and Study 2 (fed state)]. Rosmarinic acid in serum was measured by a coulometric detection method using High-Performance Liquid Chromatography electrochemical detector. The serum concentration of total rosmarinic acid peaked at 1 hour after administration of Melissa officinalis extract containing 500mg rosmarinic acid in fasted state, with a maximum serum concentration 162.20 nmol/ L. The area under the curve for intact rosmarinic acid was calculated from the serum concentration-time profile to be 832.13 nmol • hour/ L. Food intake increases area under the curve and delayed time at which the maximum serum concentration. Rosmarinic acid supplementation did not affect liver, kidney, or blood cell function parameters. No adverse event was reported by any of the participants due to the study treatment. Single dose of Melissa officinalis extract containing 500 mg rosmarinic acid appears to be safe and tolerable in healthy individuals. Food intake increased the exposure of rosmarinic acid and delayed absorption of rosmarinic acid in healthy individuals.

  18. Safety and tolerability of Panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers.

    Science.gov (United States)

    Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo; Son, Chang Gue

    2012-11-01

    Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product.

  19. Safety and Tolerability of Panax ginseng Root Extract: A Randomized, Placebo-Controlled, Clinical Trial in Healthy Korean Volunteers

    Science.gov (United States)

    Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo

    2012-01-01

    Abstract Objectives Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. Methods This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Results Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. Conclusions P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product. PMID:22909282

  20. Multidimensional visualization of healthy and sensitized rabbit knee tissues by means of confocal microscopy.

    Science.gov (United States)

    Rudys, Romualdas; Bagdonas, Saulius; Kirdaitė, Gailutė; Papečkienė, Jurga; Rotomskis, Ričardas

    2015-05-01

    This study combines several fluorescence detection methods to distinguish structural features of the synovium and cartilage tissues and to visualize the localization of endogenous porphyrins in the sensitized tissues. Specimens of synovium and cartilage tissues obtained from rabbits with antigen-induced monoarthritis after intra-articular 5-aminolevulinic acid methyl ester injection and those from healthy rabbits were investigated ex vivo by means of fluorescence spectroscopy, fluorescence intensity, and lifetime microscopy. The presence of endogenous porphyrins was confirmed with the fluorescence spectra measured on sliced sensitized specimens. Application of the lifetime-gating method on fast fluorescence lifetime imaging microscopy images, allowed separate visualization of tissue structures possessing different average lifetimes. The presence of the structures has been validated by histopathological imaging based on conventional rapid hematoxylin–eosin staining of the specimens. The fluorescence lifetime of endogenous protoporphyrin IX has been assessed and employed for visualization of sensitized tissues.

  1. Heat exposure induces tissue stress in heat-intolerant, but not heat-tolerant, mice.

    Science.gov (United States)

    Islam, Aminul; Abraham, Preetha; Hapner, Christopher D; Andrews-Shigaki, Brian; Deuster, Patricia; Chen, Yifan

    2013-03-01

    We investigated the association of systemic and local tissue stress responses with heat-tolerant (TOL) levels in mice. Thirty-eight mice were assigned into control and three heat exposure groups-TOL, moderately tolerant, and intolerant (INT), based on their overall thermal responses. Real-time core temperature, blood pressure, and heart rate (HR) were assessed during heat exposure (39.5 °C) under conscious condition. Tissue samples were collected 18-22 h following heat exposure. INT mice had significantly higher peak mean arterial pressure and HR than TOL mice during heat exposure. Plasma corticosterone levels were significantly higher in INT than in control mice. No significant changes in plasma cytokines or markers of oxidative status were observed. INT mice showed significant increases in HSP72 and HSP90 protein and mRNA levels in liver, heart, and gastrocnemius muscles compared to TOL and control mice. In contrast, INT mice had significantly lower heat shock factor 1 and glucocorticoid receptor protein and mRNA levels in these tissues than TOL and control mice. These results indicate that acute heat exposure induces stress responses in various tissues of INT mice, but not TOL mice. Upregulation of stress proteins by acute heat exposure involves both transcriptional and translational pathways.

  2. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men.

    Science.gov (United States)

    Asmar, Ali; Asmar, Meena; Simonsen, Lene; Madsbad, Sten; Holst, Jens J; Hartmann, Bolette; Sorensen, Charlotte M; Bülow, Jens

    2017-02-01

    In healthy subjects, we recently demonstrated that during acute administration of GLP-1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP-1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and/or splanchnic tissues. Nine healthy men were examined twice in random order during a 2-hour infusion of either GLP-1 (1.5 pmol kg(-1) min(-1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra-arterial blood pressure. Subcutaneous, abdominal adipose tissue blood flow (ATBF) was measured by the (133)Xenon clearance technique. Leg and splanchnic blood flow were measured by Fick's Principle, using indocyanine green as indicator. In the GLP-1 study, cardiac output increased significantly together with a significant increase in arterial pulse pressure and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP-1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP-1 increases cardiac output acutely due to a GLP-1-induced vasodilation in adipose tissue and skeletal muscle together with an increase in cardiac work.

  3. Diurnal variation of connective tissue metabolites in early and long-standing rheumatoid arthritis and in healthy individuals

    DEFF Research Database (Denmark)

    Lottenburger, T; Junker, P; Hørslev-Petersen, K

    2011-01-01

    To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals.......To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals....

  4. Polarimetry based partial least square classification of ex vivo healthy and basal cell carcinoma human skin tissues.

    Science.gov (United States)

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ikram, Masroor

    2016-06-01

    Optical polarimetry was employed for assessment of ex vivo healthy and basal cell carcinoma (BCC) tissue samples from human skin. Polarimetric analyses revealed that depolarization and retardance for healthy tissue group were significantly higher (ppolarimetry together with PLS statistics hold promise for automated pathology classification. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. CALCIUM AND MAGNESIUM CONTENT IN CANCEROUS AND HEALTHY TISSUES OF GASTROINTESTINAL TRACT

    Directory of Open Access Journals (Sweden)

    Marta Głogowska

    2012-10-01

    Full Text Available Studies concerning concentration of biogenic metals in tissues of digestive system are sparse and diversified. The objectives of this study were to determine the mean concentration of biogenic metals: Mg and Ca, in cancerous and normal tissues of digestive system. Research was conducted on samples taken from different segments of human digestive tract. Tissues were taken during biopsy, surgery, and post-mortem from Military Hospital and PROSMED Health Center Patients’ located in Cracow. Samples were mineralized by wet digestion. First, they were dried and after dry mass were obtained the samples were put into digestion flasks and 1cm3 of nitric acid 65% was added to each of them. The samples were heated for about 2 hours, at 105°C. Mineralized material was moved to tubes with a capacity of 10 cm3 and filled with distilled water up to this volume. The resulting solutions were used to analyze the content of selected elements by FAAS method. The results are expressed in micrograms per gram of dry weight of tissue (µg•g-1d.m.. Average calcium content is higher in the tissues of the gastrointestinal tract of both healthy women (15890,28 µg•g-1d.m. and men (13040,24 µg•g-1d.m. in comparison with tumor tissues of the gastrointestinal tract of women (5365,19 µg•g-1 d.m. and men (2459,42 µg•g-1d.m.. Average magnesium content is higher in the tissues of the gastrointestinal tract of both healthy women (2887,19 µg•g-1 d.m. and men (1112,69 µg•g-1 d.m., in comparison with gastrointestinal cancerous tissues of women (1146,77 µg•g-1 d.m. and men (621,42 µg•g-1 d.m.. It was shown that differences between calcium and magnesium contents in the digestive tract tissues depend on the state of health - significantly higher contents of Ca and Mg were present in the tissues of healthy men and women in comparison to the tissues of men and women with digestive tract cancer. Magnesium and calcium have protective properties (they prevent the

  6. Fatty acid composition of brown adipose tissue in genetically heat-tolerant FOK rats

    Science.gov (United States)

    Ohno, T.; Furuyama, F.; Kuroshima, A.

    The phospholipid fatty acid composition of brown adipose tissue (BAT) was examined in inbred heat-tolerant FOK rats and compared with that in conventional Wistar rats not previously exposed to heat. The FOK rats showed higher unsaturation states, as indicated by higher levels of polyunsaturated fatty acids and a higher unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio. This higher level of unsaturation was characterized by the higher amount of polyunsaturated fatty acids such as linoleic acid, arachidonic acid and docosahexaenoic acid. It may be concluded that the increased docosahexaenoic acid level in BAT phospholipids brings about the hyperplasia of BAT, causing an enhancement of its in vivo thermogernic activity as well as the systemic non-shivering thermogenesis observed in heat-tolerant FOK rats.

  7. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    Directory of Open Access Journals (Sweden)

    Aimee L. Dordevic

    2015-07-01

    Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

  8. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults.

    Science.gov (United States)

    Dordevic, Aimee L; Pendergast, Felicity J; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K; Larsen, Amy E; Sinclair, Andrew J; Cameron-Smith, David

    2015-07-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

  9. Effects of chronic caffeine administration on blood glucose levels and on glucose tolerance in healthy and diabetic rats.

    Science.gov (United States)

    Urzúa, Z; Trujillo, X; Huerta, M; Trujillo-Hernández, B; Ríos-Silva, M; Onetti, C; Ortiz-Mesina, M; Sánchez-Pastor, E

    2012-01-01

    To analyse the effect of chronic caffeine use on risk reduction and prognosis of diabetes mellitus. In this 60-day study, five groups of 11 healthy male Wistar rats were selected to receive one of four doses (37.5, 56.2, 75.0 or 93.0 mg/kg per day) of caffeine orally or no caffeine (control). The effect of caffeine on glycaemia and glucose tolerance was evaluated. After 15 days, each group was treated with 60 mg/kg of streptozotocine to induce diabetes mellitus, and glycaemia and glucose tolerance were assessed for a further 45 days. In nondiabetic rats, caffeine had no effect on blood glucose. Compared with controls, the fasting blood glucose levels declined significantly in two caffeine-treated groups (93.0 mg/kg per day and 56.2 mg/kg per day) during the first 15 days following diabetes induction. Glucose tolerance was significantly improved 120 min after glucose loading in all caffeine-treated groups. The mean ± SE half-maximal effective concentration of caffeine was 35.79 ± 2.44 mg/dl. Blood glucose levels decreased, and glucose tolerance improved, in diabetic rats administered increasing doses of caffeine.

  10. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    Science.gov (United States)

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).

  11. Multivariate analysis of the scattering profiles of healthy and pathological human breast tissues

    Energy Technology Data Exchange (ETDEWEB)

    Conceicao, A.L.C.; Antoniassi, M. [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil); Cunha, D.M. [Instituto de Fisica, Universidade Federal de Uberlandia, 38400-902, Uberlandia, Minas Gerais (Brazil); Ribeiro-Silva, A. [Departamento de Patologia, HCFMRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil)

    2011-10-01

    Scattering profiles of 106 healthy and pathological human breast samples were obtained using the angular dispersive X-ray scattering technique (AD-XRD) and synchrotron radiation covering the momentum transfer interval of 0.7 nm{sup -1}{<=}q(=4{pi} sin({theta}/2)/{lambda}){<=}70.5 nm{sup -1}. Multivariate analysis in the form of discriminant analysis was applied over the whole scattering profile curve of each sample in order to build a model for breast tissue classification. The classification results were validated and compared with histological sample classification obtained by microscopy analysis. Finally, the model allows classifying correctly 91.5% of the samples and presented values of 98.5%, 89.7% and 0.90 for sensitivity, specificity and Cohen's {kappa}, respectively, in correctly differentiating between healthy and pathological tissues.

  12. Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer's disease compared to healthy control

    DEFF Research Database (Denmark)

    Jensen-Dahm, Christina; Werner, Mads Utke; Dahl, Jørgen Berg;

    2014-01-01

    Patients with Alzheimer disease (AD) report pain less frequently than their cognitively intact peers. It has been hypothesized that pain processing is altered in AD. The aim of this study was to investigate agreement and reliability of 3 pain sensitivity tests and to examine pain threshold...... and tolerance in patients with AD. We examined 29 patients with mild to moderate AD and 29 age- and gender-matched healthy control subjects with quantitative sensory testing, ie, assessments of detection threshold (warmth detection threshold [WDT]) and pain threshold (heat pain threshold [HPT], pressure...... algometry, cold pressor test), and assessments of tolerance (pressure algometry, cold pressor test). All procedures were done twice on day 1, 1 hour apart, and repeated on day 2. We found no difference between groups for WDT (patient vs control subjects: mean [95% confidence interval]: 35.5°C [33.4°C to 37...

  13. Tissue-specific expression and functional role of dehydrins in heat tolerance of sugarcane (Saccharum officinarum).

    Science.gov (United States)

    Galani, Saddia; Wahid, Abdul; Arshad, Muhammad

    2013-04-01

    Studies on the functional roles of dehydrins (DHNs) in heat tolerance of plants are scarce. This study was conducted to immunohistolocalize DHNs in leaves of heat-tolerant (CP-4333) and heat-sensitive (HSF-240) sugarcane (Saccharum officinarum L.) clones at three phenological stages in order to elucidate their putative roles under heat stress. CP-4333 indicated greater amounts of heat-stable proteins than HSF-240 under heat stress. Western blotting revealed the expression of three DHNs in CP-4333 (13- and 15-kDa peptides at 48 h and an additional 18-kDa band at 72 h) and two (13 and 15 kDa at 48 h) in HSF-240 at formative stage; two DHNs in CP-4333 (20 and 25 kDa) and one in HSF-240 (20 kDa) at grand growth stage, while two DHNs in CP-4333 (20 and 22 kDa) and one in HSF-240 (20 kDa) at maturity stage. Tissue-specific immunohistolocalization showed that DHNs were expressed in stele particularly the phloem and the cells intervening bundle sheath and vascular bundles. Furthermore, DHNs were also found scattered along the epidermal and parenchymatous cells. Recovery of sugarcane from heat stress manifested a gradual disappearance of DHNs in both the clones, being quicker in sensitive clone (HSF-240). Results suggested specific implications for DHNs synthesis. Their synthesis in epidermis appears to protect the mesophyll tissues from heat injury. When associated to vascular tissue, they tend to ensure the normal photoassimilate loading into the sieve element-companion cell complex. DHNs diminution during recovery suggested that their expression was transitory. However, prolonged retention of DHNs by tolerant clone appears to be an adaptive advantage of sugarcane to withstand heat stress.

  14. Tissue bioavailability of anthocyanins from whole tart cherry in healthy rats.

    Science.gov (United States)

    Kirakosyan, Ara; Seymour, E Mitchell; Wolforth, Janet; McNish, Robert; Kaufman, Peter B; Bolling, Steven F

    2015-03-15

    Our aim was to confirm and identify the presence of tart cherry anthocyanins in several target tissues of healthy rats. Liquid chromatography-mass spectrometry analysis was employed for detection and characterisation of anthocyanin metabolites. It was shown that four native anthocyanins, namely cyanidin 3-glucosylrutinoside, cyanidin 3-rutinoside, cyanidin 3-rutinoside 5-β-D-glucoside, and peonidin 3-rutinoside were differentially distributed among targeted tissues of rats. Bladder and kidney contained more total anthocyanins than all other tissues analysed. It was also revealed that the bioavailability pattern of these native anthocyanins among tissues is varied. The highest concentration of individual anthocyanin cyanidin 3-glucosylrutinoside (2339 picograms/gram of tissue) was detected in bladder, followed by cyanidin 3-rutinoside 5-β-d-glucoside (916 picograms/gram) in the liver of rats. Although the diverse distribution of tart cherry anthocyanins in different rat tissues still requires further explanation, it may provide an evidentiary link between tissue bioavailability and health-enhancing properties of anthocyanins at target sites.

  15. Noninvasive estimation of tissue edema in healthy volunteers and in patients suffering from heart failure

    Science.gov (United States)

    Gurfinkel, Yuri I.; Mikhailov, Valery M.; Kudutkina, Marina I.

    2004-06-01

    Capillaries play a critical role in cardiovascular function as the point of exchange of nutrients and waste products between tissues and circulation. A common problem for healthy volunteers examined during isolation, and for the patients suffering from heart failure is a quantitative estimation tissue oedema. Until now, objective assessment body fluids retention in tissues did not exist. Optical imaging of living capillaries is a challenging and medically important scientific problem. Goal of the investigation was to study dynamic of microcriculation parameters including tissue oedema in healthy volunteers during extended isolation and relative hypokinesia as a model of mission to the International Space Station. The other aim was to study dynamic of microcirculation parameters including tissue oedema in patients suffering from heart failure under treatment. Healthy volunteers and patients. We studied four healthy male subjects at the age of 41, 37, 40, and 48 before the experiment (June 1999), and during the 240-d isolation period starting from July3, 1999. Unique hermetic chambers with artidicial environmental parameters allowed performing this study with maximum similarity to real conditions in the International Space Station (ISS). With the regularity of 3 times a week at the same time, each subject recorded three video episodes with the total length of one-minute using the optical computerized capillaroscope for noninvasive measurement of the capillary diameters sizes, capillary blood velocity as well as the size of the perivascular zone. All this parameters of microcirculation determined during three weeks in 15 patients (10 male, 5 female, aged 62,2+/-8,8) suffering from heart failure under Furosemid 40 mg 2 times a week, as diuretic. Results. About 1500 episodes recorded on laser disks and analyzed during this experiment. Every subject had wave-like variations of capillary blood velocity within the minute, week, and month ranges. It was found that the

  16. Long-term gastrointestinal tolerance of NUTRIOSE®FB in healthy men

    NARCIS (Netherlands)

    Pasman, W.; Wils, D.; Saniez, M.H.; Kardinaal, A.

    2006-01-01

    Objective: To determine the gastrointestinal (GI) tolerance of NUTRIOSE®FB in men. Design: A randomized, placebo-contro lled, parallel, double-blind study. Setting: The metabolic ward of TNO Quality of Life. Subjects: Forty-eight subjects started the study: 16 men participated in one of the three tr

  17. Ventricular synchronicity: observations comparing pulse flow and tissue Doppler assessment in a Chinese healthy adult cohort

    Institute of Scientific and Technical Information of China (English)

    QUAN Xin; ZHU Tian-gang; GUO Shi; MA Jian-xin; WANG Xin; GUO Ji-hong

    2012-01-01

    Background Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy,but detailed knowledge about cardiac timing in healthy persons is scarce.Therefore,in the current study,we sought to investigate the physiological status of interventricular synchronicity using pulse wave flow and tissue Doppler imaging in a healthy Chinese population.Methods Eighty-eight healthy volunteers underwent standard flow and tissue Doppler echocardiographic examinations.Ventricular inflow and outflow pulse wave flow Doppler patterns were recorded together with annulus pulse tissue Doppler imaging.Time intervals from the beginning of the QRS complex to the onset,peak and end of each wave were measured.Results The onsets of systole between left and right ventricles were highly synchronized by both imaging modalities.However,the left ventricle reached the peak flow ejection and peak mechanical contraction earlier than the right ventricle,(165.61±26.23) ms vs.(204.3±34.55) ms (P <0.01) and (133.62±26.19) ms vs.(191.25±38.47) ms (P <0.01).Time to peak early diastolic relaxation was earlier in the left ventricle than in the right heart,(500.23±56.52) me vs.(524.94±47.42) ms (P <0.01).Conclusions Left and right ventricles were well synchronized at the onsets of systole and diastole even though interventricular peak systolic and peak early diastolic dyssynchrony was observed in healthy people by pulse wave Doppler imaging.In addition,diastolic timing events were slightly affected by age and gender.

  18. Glandular breast tissue volume by magnetic resonance imaging in 100 healthy peripubertal girls

    DEFF Research Database (Denmark)

    Fugl, Louise; Hagen, Casper P; Mieritz, Mikkel G

    2016-01-01

    BACKGROUND: Appearance of glandular breast tissue may be difficult to distinguish from fat tissue by palpation, especially in obese girls. To our knowledge, validation of the clinical assessment of pubertal breast stages by magnetic resonance imaging (MRI) has never been performed. Our objective....... METHODS: Glandular breast tissue volume quantified by MRI and breast stage evaluation was performed in 100 healthy peripubertal girls. Circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and estradiol were measured by immunoassays. Ovarian volume, uterine volume....... The best parameters to distinguish prepubertal girls from girls with breast development were: LH (area under the curve (AUC) by receiver operating characteristic analysis = 0.871), inhibin B (AUC = 0.847) and estradiol (AUC = 0.830). CONCLUSION: Clinical palpation reliably detects the presence of glandular...

  19. Pharmacokinetics, pharmacodynamics, and tolerability of ACT-077825, a new direct renin inhibitor after multiple-ascending doses in healthy subjects.

    Science.gov (United States)

    Nicolas, Laurent B; Gutierrez, Marcelo; Binkert, Christoph; Dingemanse, Jasper

    2013-01-01

    This study was conducted to characterize the multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-077825, a new direct renin inhibitor, in healthy male subjects. In this single-center, double-blind, placebo-controlled, active-controlled (20 mg of enalapril), randomized multiple-ascending dose study, ACT-077825 was administered once a day. for 7 days in the 50-1000 mg dose range to sodium- and potassium-restricted subjects. ACT-077825 pharmacokinetics on days 1 and 7 were characterized by dose-proportional increases in Cmax and AUCτ. At steady state, accumulation was modest (1.5- to 1.7-fold). Enalapril caused an increase in plasma active renin concentration and plasma renin activity (PRA). ACT-077825 dose dependently increased active renin on days 1 and 7 and inhibited PRA dose dependently only on day 1. On day 7, the maximal PRA inhibition was attained after 250 mg of ACT-077825. In contrast to enalapril, ACT-077825 did not induce any consistent lowering effect on blood pressure when compared with placebo. Of the reported adverse events, diarrhea, headache, and postural dizziness were more frequent. The incidence of diarrhea was greater in the 1000-mg group and a dose of 500 mg of ACT-077825 was identified as the maximum tolerated dose. Overall, pharmacokinetic, pharmacodynamic, and tolerability profiles warrant the further investigation of ACT-077825 in patients with hypertension.

  20. Textural analysis of optical coherence tomography skin images: quantitative differentiation between healthy and cancerous tissues

    Science.gov (United States)

    Adabi, Saba; Conforto, Silvia; Hosseinzadeh, Matin; Noe, Shahryar; Daveluy, Steven; Mehregan, Darius; Nasiriavanaki, Mohammadreza

    2017-02-01

    Optical Coherence Tomography (OCT) offers real-time high-resolution three-dimensional images of tissue microstructures. In this study, we used OCT skin images acquired from ten volunteers, neither of whom had any skin conditions addressing the features of their anatomic location. OCT segmented images are analyzed based on their optical properties (attenuation coefficient) and textural image features e.g., contrast, correlation, homogeneity, energy, entropy, etc. Utilizing the information and referring to their clinical insight, we aim to make a comprehensive computational model for the healthy skin. The derived parameters represent the OCT microstructural morphology and might provide biological information for generating an atlas of normal skin from different anatomic sites of human skin and may allow for identification of cell microstructural changes in cancer patients. We then compared the parameters of healthy samples with those of abnormal skin and classified them using a linear Support Vector Machines (SVM) with 82% accuracy.

  1. How Fast Is Recovery of Impaired Glucose Tolerance after 21-Day Bed Rest (NUC Study in Healthy Adults?

    Directory of Open Access Journals (Sweden)

    Martina Heer

    2014-01-01

    Full Text Available Aim. We hypothesized that 4 days of normal daily activity after 21 days of experimental bed rest (BR will not reverse BR induced impaired glucose tolerance. Design. Glucose tolerance of seven male, healthy, untrained test subjects (age: 27.6 (3.3 years (mean (SD; body mass: 78.6 (6.4 kg; height: 1.81 (0.04 m; VO2 max: 39.5 (5.4 ml/kg body mass/min was studied. They stayed twice in the metabolic ward (crossover design, 21 days in bed and 7 days before and after BR each. Oral glucose tolerance tests were applied before, on day 21 of BR, and 5 and 14 days after BR. Results. On day 21 of BR, AUC120 min of glucose concentration was increased by 28.8 (5.2% and AUC120 min of insulin by 35.9 (10.2% (glucose: P<0.001; insulin: P=0.02. Fourteen days after BR, AUC120 min of serum insulin concentrations returned to pre-bed-rest concentrations (P=0.352 and AUC120 min of glucose was still higher (P=0.038. Insulin resistance did not change, but sensitivity index was reduced during BR (P=0.005. Conclusion. Four days of light physical workload does not compensate inactivity induced impaired glucose tolerance. An individually tailored and intensified training regime is mandatory in patients being in bed rest to get back to normal glucose metabolism in a reasonable time frame.

  2. Fourier-transformed infrared spectroscopy: a tool to identify gross chemical changes from healthy to yellow band disease tissues.

    Science.gov (United States)

    Guerra, Mayamarú; López, Maria Antonieta; Estéves, Ivan; Zubillaga, Ainhoa L; Cróquer, Aldo

    2014-01-16

    Yellow band disease (YBD) is a common and wide-spread Caribbean syndrome that affects the genus Orbicella, a group of species that constitute the framework of Caribbean coral reefs. Previous studies have shown that the structure and function of bacterial assemblages vary between healthy tissues and YBD lesions; however, how the molecular composition of tissues varies as tissues transition from healthy to YBD has not been determined before. The present study provides the first survey of macromolecules found from healthy (H), apparently healthy (AH), transition (TR) and YBD tissues of Orbicella faveolata. For this, we used Fourier-transformed mid-infrared spectroscopy (FTIR) to compare absorption profiles as a proxy for the gross molecular composition of decalcified H, AH and YBD tissues. We found a significantly higher level of infrared absorption for bands assigned to lipids in H tissues compared to YBD tissues, suggesting that lipid compounds are more abundant in compromised tissues in relation to other macromolecules. We also found a lower level of intensity of bands assigned to carbohydrates and proteins in YBD tissues, compared to H and AH tissues. A similar pattern was observed for phospholipidic compounds in relation to fatty acids. This study is the first to show that healthy and YBD-compromised tissues have different infrared absorption profiles, suggesting that alterations in the biochemical composition occur during pathogenesis. Future studies should focus on determining the actual concentration of these compounds in H, AH, TR and YBD tissues and on testing the role of translocation of photoassimilates from H tissues and/or from endolithic algae to YBD tissues.

  3. Supracrestal gingival tissue: assessing relation with periodontal biotypes in a healthy periodontium.

    Science.gov (United States)

    Arora, Ritika; Narula, Satish C; Sharma, Rajinder K; Tewari, Shikha

    2013-01-01

    This cross-sectional study assessed the variability in supracrestal gingival tissue (SGT) dimensions in a healthy periodontium. SGT dimensions were evaluated for differences across various locations, tooth types, and periodontal biotypes. All measurements were made with a vernier caliper to the nearest 0.1 mm. A total of 1,932 sites in 366 teeth were statistically analyzed. Median overall SGT was recorded as 3.50 mm with a range from 1.80 to 6.20 mm. The thick-flat biotype exhibited greater median SGT than the thinscalloped biotype. When planning crown lengthening surgery, periodontal biotype may have a significant role in determining SGT dimensions.

  4. Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis.

    Science.gov (United States)

    Barbour, April; Schmidt, Stephan; Sabarinath, Sreedharan Nair; Grant, Maria; Seubert, Christoph; Skee, Donna; Murthy, Bindu; Derendorf, Hartmut

    2009-07-01

    Ceftobiprole is a promising new broad-spectrum cephalosporin with activity against several multidrug-resistant gram-positive and gram-negative species, including methicillin-resistant Staphylococcus aureus. In order to make efficacy predications against these resistant bacteria in soft-tissue infections, i.e., skin and skin structure infections, ceftobiprole's ability to reach the site of action should be explored. Therefore, a microdialysis study was conducted in 12 healthy volunteers to determine the penetration of ceftobiprole into skeletal muscle and subcutaneous (s.c.) adipose tissue after a single intravenous dose of 500 mg. Plasma and tissue interstitial space fluid (ISF) drug concentrations were measured for 24 h from the start of the 2-h intravenous infusion. Pharmacokinetic parameters were determined using noncompartmental analysis. The penetration of ceftobiprole into the ISF of tissues was assessed by comparing the ratios between tissue and plasma of the free drug area under the concentration-time curve (fAUC). It was found that ceftobiprole distributes into the muscle (fAUC(muscle)/fAUC(plasma) of 0.69 +/- 0.13) and s.c. adipose tissue (fAUC(s.c.adipose)/fAUC(plasma) of 0.49 +/- 0.28). The concentrations in both skeletal muscle and s.c. adipose tissue met the efficacy breakpoint (percentage of the time that free drug concentrations remained above the MIC) for at least 40% of the 8-h dosing interval for organisms with a MIC of 2 mg/liter. Therefore, ceftobiprole qualifies as a potential agent with drug penetration capabilities to treat complicated skin and skin structure infections due to both gram-negative and gram-positive pathogens with MICs equal to or below 2 mg/liter.

  5. Effect of Pseudocereal-Based Breakfast Meals on the First and Second Meal Glucose Tolerance in Healthy and Diabetic Subjects

    Science.gov (United States)

    Gabrial, Shreef G. N.; Shakib, Marie-Christine R.; Gabrial, Gamal N.

    2016-01-01

    . The blood glucose concentration after consuming quinoa meal showed a high peak at 30 min similar to that of WWB reference meal. This peak resulted in a high glycemic index (GI) for quinoa (89.4). The GI of buckwheat recorded a low value (26.8). CONCLUSION: The two studied pseudocereals; quinoa and buckwheat have high potential to improve glucose tolerance at the first and second meal (lunch) and are recommended to be introduced in our daily diet for healthy and diabetic subjects. PMID:28028392

  6. Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs: a blind, randomized, placebo-controlled study.

    Science.gov (United States)

    Maina, E; Pelst, M; Hesta, M; Cox, E

    2017-01-18

    Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 μg of peanut extract daily for 7 to 14 days. All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions

  7. Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies.

    Directory of Open Access Journals (Sweden)

    Claus Lindner

    Full Text Available The in vivo optical and hemodynamic properties of the healthy (n = 22 and pathological (n = 2 human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS and diffuse correlation spectroscopy (DCS system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs' at three wavelengths (690, 785 and 830 nm to derive total hemoglobin concentration (THC and oxygen saturation (StO2. DCS measured the microvascular blood flow index (BFI. Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s, while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%, yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

  8. Polarization birefringence measurements for characterizing the myocardium, including healthy, infarcted, and stem-cell-regenerated tissues

    Science.gov (United States)

    Wood, Michael F. G.; Ghosh, Nirmalya; Wallenburg, Marika A.; Li, Shu-Hong; Weisel, Richard D.; Wilson, Brian C.; Li, Ren-Ke; Vitkin, I. Alex

    2010-07-01

    Myocardial infarction leads to structural remodeling of the myocardium, in particular to the loss of cardiomyocytes due to necrosis and an increase in collagen with scar formation. Stem cell regenerative treatments have been shown to alter this remodeling process, resulting in improved cardiac function. As healthy myocardial tissue is highly fibrous and anisotropic, it exhibits optical linear birefringence due to the different refractive indices parallel and perpendicular to the fibers. Accordingly, changes in myocardial structure associated with infarction and treatment-induced remodeling will alter the anisotropy exhibited by the tissue. Polarization-based linear birefringence is measured on the myocardium of adult rat hearts after myocardial infarction and compared with hearts that had received mesenchymal stem cell treatment. Both point measurement and imaging data show a decrease in birefringence in the region of infarction, with a partial rebound back toward the healthy values following regenerative treatment with stem cells. These results demonstrate the ability of optical polarimetry to characterize the micro-organizational state of the myocardium via its measured anisotropy, and the potential of this approach for monitoring regenerative treatments of myocardial infarction.

  9. Dielectric characterization of healthy and malignant colon tissues in the 0.5-18 GHz frequency band

    Science.gov (United States)

    Fornes-Leal, A.; Garcia-Pardo, C.; Frasson, M.; Pons Beltrán, V.; Cardona, N.

    2016-10-01

    Several reports over the last few decades have shown that the dielectric properties of healthy and malignant tissues of the same body organ usually show different values. However, no intensive dielectric studies of human colon tissue have been performed, despite colon cancer’s being one of the most common types of cancer in the world. In order to provide information regarding this matter, a dielectric characterization of healthy and malignant colon tissues is presented. Measurements are performed on ex vivo surgery samples obtained from 20 patients, using an open-ended coaxial probe in the 0.5-18 GHz frequency band. Results show that the dielectric constant of colon cancerous tissue is 8.8% higher than that of healthy tissues (p  =  0.002). Besides, conductivity is about 10.6% higher, but in this case measurements do not have statistical significance (p  =  0.038). Performing an analysis per patient, the differences in dielectric constant between healthy and malignant tissues appear systematically. Particularized results for specific frequencies (500 MHz, 900 MHz, 2.45 GHz, 5 GHz, 8.5 GHz and 15 GHz) are also reported. The findings have potential application in early-stage cancer detection and diagnosis, and can be useful in developing new tools for hyperthermia treatments as well as creating electromagnetic models of healthy and cancerous tissues.

  10. Tolerability of intramuscular and intradermal delivery by CELLECTRA(®) adaptive constant current electroporation device in healthy volunteers.

    Science.gov (United States)

    Diehl, Malissa C; Lee, Jessica C; Daniels, Stephen E; Tebas, Pablo; Khan, Amir S; Giffear, Mary; Sardesai, Niranjan Y; Bagarazzi, Mark L

    2013-10-01

    DNA vaccines are being developed as a potentially safe and effective immunization platform. However, translation of DNA vaccines into a clinical setting has produced results that have fallen short of those generated in a preclinical setting. Various strategies are being developed to address this lack of potency, including improvements in delivery methods. Electroporation (EP) creates transient increases in cell membrane permeability, thus enhancing DNA uptake and leading to a more robust immune response. Here, we report on the safety and tolerability of delivering sterile saline via intramuscular (IM) or intradermal (ID) injection followed by in vivo electroporation using the CELLECTRA(®) adaptive constant current device in healthy adults from two open-label studies. Pain, as assessed by VAS, was highest immediately after EP but diminishes by about 50% within 5 min. Mean VAS scores appear to correlate with the amount of energy delivered and depth of needle insertion, especially for intramuscular EP. Mean scores did not exceed 7 out of 10 or 3 out of 10 for IM and ID EP, respectively. The majority of adverse events included mild to moderate injection site reactions that resolved within one day. No deaths or serious adverse events were reported during the course of either study. Overall, injection followed by EP with the CELLECTRA(®) device was well-tolerated and no significant safety concerns were identified. These studies support the further development of electroporation as a vaccine delivery method to enhance immunogenicity, particularly for diseases in which traditional vaccination approaches are ineffective.

  11. Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects.

    Science.gov (United States)

    Shen, Zancong; Gillen, Michael; Miner, Jeffrey N; Bucci, Gail; Wilson, David M; Hall, Jesse W

    2017-01-01

    Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males. This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study. Panels of eight male subjects received a single oral dose of verinurad or placebo in either a fasted or fed state; panels of 10-12 male subjects received ascending doses of once-daily verinurad or placebo in a fasted state for 10 days. Serial blood and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse event (AE) reports, laboratory tests, vital signs, and electrocardiograms (ECGs). A total of 81 adult males completed the study. Following single doses of verinurad, maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a dose-proportional manner; Cmax occurred at 0.5-0.75 hours and 1.25 hours in the fasted and fed states, respectively. Food decreased AUC by 23% and Cmax by 37%-53%. There was a modest accumulation of verinurad following multiple daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single dose) and 61% (10 mg, multiple dose). The increase in urinary excretion of uric acid was greatest in the first 6 hours after dosing and was still evident ≥24 hours for verinurad doses ≥2 mg. Verinurad was well tolerated at all doses. No serious AEs, severe AEs, discontinuations due to AEs, or clinically significant laboratory or ECG abnormalities were reported. Single and multiple doses of verinurad were well tolerated, absorption was rapid, and exposure was dose proportional. Verinurad increased urinary uric acid elimination and resulted in sustained reductions in serum urate. These data support further clinical evaluation of once-daily verinurad as a treatment for

  12. The effect of mirtazapine on gastric accommodation, gastric sensitivity to distention, and nutrient tolerance in healthy subjects.

    Science.gov (United States)

    Carbone, F; Vanuytsel, T; Tack, J

    2017-07-11

    Disturbances of gastric motor function of functional dyspepsia (FD) have been implicated in the pathogenesis of the symptoms, and hence, motility modifying agents are considered for its treatment. Mirtazapine was recently shown to improve symptoms and increase nutrient tolerance in FD patients with weight loss. We aim to evaluate the effect of mirtazapine on gastric sensorimotor function in healthy volunteers (HV). Thirty-one HV underwent an intragastric pressure (IGP) and barostat measurements on separate days before and after 3 weeks of placebo or mirtazapine (15 mg). Gastric compliance, sensitivity and accommodation (GA) measured by the barostat. GA was quantitated as the difference (delta) in intra-balloon volume before and after ingestion of 200 mL of a nutrient drink (ND). GA measured by IGP was quantitated as the drop of IGP from baseline during the intragastric infusion of ND until maximal satiation. Mirtazapine significantly increased the bodyweight of subjects (67.8±3.7 to 69.1±3.7 kg; P=.01). Barostat results showed no effect on gastric compliance, sensitivity, and GA. Nutrient tolerance was not affected after treatment (1170±129.4 vs 1104±133.6 kcal; P=.4), and mirtazapine was associated with lower symptom ratings. The IGP drop during meal ingestion was significantly suppressed (area under the curve: -43.3±4.5 mm Hg vs -28.9±3.1 mm Hg; P=.005). In HVs, the occurrence of weight gain and decreased meal-induced symptoms in spite of a suppressed meal-induced IGP drop, point towards a central mode of action. Mirtazapine does not display changes in gastric sensorimotor function that could explain its beneficial effects on symptoms and nutrient tolerance in FD. © 2017 John Wiley & Sons Ltd.

  13. Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows

    Directory of Open Access Journals (Sweden)

    Foley Cathriona

    2012-09-01

    Full Text Available Abstract Background All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR. Results mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P P SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum. Conclusions The results of this study reveal an early activation of the immune response which undergoes a temporal functional change toward tissue proliferation and regeneration during endometrial involution in healthy postpartum cows. These molecular changes mirror the activation and resolution of endometrial inflammation during involution previously classified by the degree of neutrophil infiltration. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes may become potential markers for resolution of endometrial inflammation in

  14. Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khlifi, Rim, E-mail: rimkhlifi@yahoo.fr [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia); Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Olmedo, Pablo; Gil, Fernando [Department of Legal Medicine and Toxicology, University of Granada (Spain); Hammami, Bouthaina; Chakroun, Amine [Department of Otorhinolaryngology, HUC Habib Borguiba Hospital, Sfax (Tunisia); Rebai, Ahmed [Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Hamza-Chaffai, Amel [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia)

    2013-05-01

    Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p < 0.05), respectively. Tumor tissue metal levels were higher in men than in women. As and Cd levels in tumor and healthy tissue samples of patients smokers are significantly higher than those of non-smokers (p < 0.05). A strong effect of cumulative smoking as expressed in the number of pack per year, and tumor tissue Cd levels were positively associated with three groups of age (< 40, 51–60 and > 60 years) in both never-smokers and ever-smokers (< 20 and ≥ 20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population. - Highlights: ► Heavy metal levels in tumor tissues were higher than those in healthy tissues. ► Tumor tissue Cd levels were positively associated with age in smokers. ► Tumor tissue metal levels were higher in men than in women. ► The highest Cd and Cr concentrations among workers were observed in tumor tissues

  15. Steady-state pharmacokinetics and tolerability of modafinil given alone or in combination with methylphenidate in healthy volunteers.

    Science.gov (United States)

    Hellriegel, E T; Arora, S; Nelson, M; Robertson, P

    2001-08-01

    The potential for a pharmacokinetic (PK) drug-drug interaction between modafinil and methylphenidate, each at steady state, was investigated in an open-label, randomized, single-period study in 32 healthy male and female volunteers. All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received 20 mg of methylphenidate orally 8 hours after their modafinil dose. PK profiles of modafinil were obtained on Days 21 and 28 and compared between the two groups. There were no statistically significant differences between the treatment groups in the mean changes in PK parameters for modafinil. Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that administration of low-dose methylphenidate 8 hours after treatment with modafinil does not appear to alter the steady-state pharmacokinetics of modafinil in healthy volunteers.

  16. Pharmacokinetics, Pharmacodynamics, Pharmacogenomics, Safety, and Tolerability of Avatrombopag in Healthy Japanese and White Subjects.

    Science.gov (United States)

    Nomoto, Maiko; Pastino, Gina; Rege, Bhaskar; Aluri, Jagadeesh; Ferry, Jim; Han, David

    2017-03-24

    Avatrombopag, an orally administered, small-molecule thrombopoietin receptor (c-Mpl) agonist, is currently in clinical development for the potential treatment of severe thrombocytopenia in patients with chronic liver disease undergoing an elective procedure. The objectives of this study were to characterize and compare the pharmacokinetics (including the food effect) and pharmacodynamics (platelet count) of avatrombopag following single doses in Japanese and white subjects. Following single dosing under fasted and fed conditions, mean peak concentrations occurred at 5 to 8 hours and subsequently declined with a half-life of 16 to 18 hours in Japanese and white subjects. Administration with food did not alter the rate or extent of avatrombopag absorption but substantially reduced pharmacokinetic variability relative to the fasted state. CYP2C9 polymorphism (*2, *3) was associated with higher pharmacokinetic variability but not with any clinically important effect on variability in platelet response. Plasma exposures of avatrombopag increased in a dose-proportional manner over the dose range tested. After a single dose, platelet count increased in a dose-related manner, reaching a maximum by day 11 and returning to baseline levels by day 27. No clinically important differences were found when avatrombopag pharmacokinetics and pharmacodynamics were compared between Japanese and white subjects. Administration of avatrombopag was generally well tolerated. © 2017, The American College of Clinical Pharmacology.

  17. Insect stings to change gear for healthy plant: Improving maize drought tolerance by whitefly infestation.

    Science.gov (United States)

    Park, Yong-Soon; Ryu, Choong-Min

    2016-05-03

    Since plants first appeared about 1.1 billion years ago, they have been faced with biotic and abiotic stresses in their environment. To overcome these stresses, plants developed defense strategies. Accumulating evidence suggests that the whitefly [Bemisia tabaci (Genn.)] affects the regulation of plant defenses and physiology. A recent study demonstrates that aboveground whitefly infestation positively modulates root biomass and anthocyanin pigmentation on brace roots of maize plants (Zea mays L.). In agreement with these observations, indole-3-acetic acid (IAA) and jasmonic acid (JA) contents and the expression of IAA- and JA-related genes are higher in whitefly-infested maize plants than in non-infected control plants. Interestingly, the fresh weight of whitefly-infested maize plants is approximately 20% higher than in non-infected control plants under water stress conditions. Further investigation has revealed that hydrogen peroxide (H2O2) accumulates in whitefly-infested maize plants after water stoppage. Taken together, these results suggest that activation of phytohormones- (i.e., IAA and JA) and H2O2-mediated maize signaling pathways triggered by aboveground whitefly infestation promotes drought resistance. They also provide an insight into how inter-kingdom interactions can improve drought tolerance in plants.

  18. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study.

    Science.gov (United States)

    Fork, F T; Lafolie, P; Tóth, E; Lindgärde, F

    2000-05-01

    Clopidogrel is a new antiplatelet agent that offers increased protection over aspirin in preventing vascular ischaemic events in patients with symptomatic atherosclerosis. In a large, randomized, international study of clopidogrel and aspirin (n = 19,185 patients) clopidogrel was associated with a lower incidence of gastrointestinal adverse events, including gastrointestinal haemorrhage and hospitalizations because of gastrointestinal haemorrhage. The aim of the study was to determine whether macroscopic differences in the gastric mucosa between aspirin- and clopidogrel-treated subjects could be detected by gastroscopy after short-term treatment. Thirty-six healthy volunteers were randomized in a double-blind, double-dummy, parallel design, to 75 mg/day of clopidogrel or 325 mg/day of aspirin for 8 days. Gastroscopy was performed at base line before administration of study drug and directly after treatment completion. Gastroduodenal effects were measured in accordance with a modified Lanza scale. At base line no difference between the groups was detected (median Lanza score, 0.0 in both groups). At the end of treatment the aspirin group showed a median score of 7.5, and the clopidogrel group showed an unchanged median score of 0.0 (P < 0.001). In the aspirin group 13 individuals reported 19 adverse events versus 8 individuals and 13 adverse events for clopidogrel, with approximately half of the adverse events being gastrointestinal in each group. No serious adverse events were reported. In contrast to aspirin, short-term treatment with clopidogrel does not induce macroscopic changes in the gastroduodenal mucosa. The study results show that in patients without gastroduodenal disease clopidogrel, but not aspirin, does not induce any gastroscopically evident erosions during short-term treatment.

  19. Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo‐Controlled Studies in Healthy Volunteers

    OpenAIRE

    2016-01-01

    Abstract We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1‒3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2, ∼20 hours). Steady state was achieved in 4 days with

  20. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects

    DEFF Research Database (Denmark)

    Hansen, K B; Vilsbøll, T; Bagger, J I

    2010-01-01

    The loss of incretin effect in patients with type 2 diabetes mellitus may be secondary to impaired glucose homeostasis. We investigated whether reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet in healthy young males...

  1. Mapping of NKp46+ cells in healthy human lymphoid and non-lymphoid tissues

    Directory of Open Access Journals (Sweden)

    Elena eTomasello

    2012-11-01

    Full Text Available Understanding Natural Killer (NK cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs expressing the retinoic acid receptor-related orphan receptor t (RORt transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORt+ILCs with a lineage-CD94-CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.

  2. Assessment of the interstitial fluid in the subcutaneous tissue of healthy adults using ultrasonography

    Directory of Open Access Journals (Sweden)

    Terumi Ueda-Iuchi

    2015-11-01

    Full Text Available Objective: Lymphoedema involves swelling, especially in the subcutaneous tissues. For lymphoedema management to be successful, it is necessary to remove the interstitial fluid. Subcutaneous echogenicity may be associated with interstitial fluid, but echogenicity is not an indicator for the evaluation of management because we do not directly compare echogenicity with the interstitial fluid. We aimed to identify an outcome indicator for the evaluation of interstitial fluid using ultrasonography. We assessed the correlation between echogenicity and transverse relaxation rate (R2 on magnetic resonance imaging. Methods: This was an observational study. Healthy adults with leg swelling after activity for >8 h were recruited. The legs of 13 women were evaluated using ultrasonography, magnetic resonance imaging and measurements of the limb circumference before and after an intervention to reduce the swelling. Results: Echogenicity in the oedema group was greater than that of the controls. Echogenicity decreased with reductions in oedema. The range of the strongest correlations with the changes in R2 occurred at echogenicity values of 48–144 (Pearson’s correlation coefficient: r = −0.63 and p < 0.01. Thus, it was possible to evaluate the interstitial fluid using echogenicity. Conclusion: The outcome indicators for the evaluation of interstitial fluid using ultrasonography were echogenicities in the range of 48–144, and these values were valid for assessing the interstitial fluid in the subcutaneous tissue.

  3. Tolerability of High-Volume Subcutaneous Injections of a Viscous Placebo Buffer: A Randomized, Crossover Study in Healthy Subjects.

    Science.gov (United States)

    Dias, Clapton; Abosaleem, Bassam; Crispino, Caroline; Gao, Bing; Shaywitz, Adam

    2015-10-01

    Monoclonal antibody biotherapeutics are often administered by subcutaneous (SC) injection. Due to dose requirements and formulation limitations, SC injections >1 mL are often required. We used a viscous placebo buffer (5 cP), characteristic of a high-concentration antibody formulation, to investigate the effect of dose volume and injection rate on the tolerability of higher-volume SC injections. In this randomized, crossover, single-center study, 48 healthy adults received one 1.2-mL bolus injection over 5 s and three 3.5-mL injections over 1, 4, and 10 min in different abdominal quadrants, with each injection separated by approximately 2 h. The primary objective was to compare pain scores associated with the injections, immediately after administration and 1 h later, using a 100-mm visual analog scale (VAS). Secondary objectives included assessment of adverse events, including injection site reactions and swelling. Mean age was 38.4 (11.6) years and 20 subjects (42%) were female. Lowest mean VAS score was for the 10-min (6.83 mm) and highest for the 1-min injection (19.13 mm). One hour after administration, mean VAS scores were injections. Swelling was similar among the three 3.5-mL injections. After needle removal, leakage occurred following 14 (29%) 1.2-mL injections, eight (17%) 4-min injections, five (10%) 1-min injections, and four (8%) 10-min injections. Fifteen subjects (31%) experienced an adverse event, none of which was serious, fatal, or led to study discontinuation. All injection durations were well tolerated, suggesting a single large-volume SC injection of a biotherapeutic agent could be used instead of multiple injections.

  4. Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects

    Science.gov (United States)

    Shin, Dongseong; Lee, SeungHwan; Yi, Sojeong; Yoon, Seo Hyun; Cho, Joo-Youn; Bahng, Mi Young; Jang, In-Jin; Yu, Kyung-Sang

    2017-01-01

    Objective DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. Methods A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. Results After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2–3 h and was eliminated with terminal elimination half-life of 17.9–28.7 h. The mean renal clearance was 3.7–5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20–80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized Cmax and AUC0–t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. Conclusion In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20–80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less. PMID:28331291

  5. Weight cycling increases T-cell accumulation in adipose tissue and impairs systemic glucose tolerance.

    Science.gov (United States)

    Anderson, Emily K; Gutierrez, Dario A; Kennedy, Arion; Hasty, Alyssa H

    2013-09-01

    Obesity is one of the leading causes of morbidity in the U.S. Accumulation of proinflammatory immune cells in adipose tissue (AT) contributes to the development of obesity-associated disorders. Weight loss is the ideal method to counteract the negative consequences of obesity; however, losses are rarely maintained, leading to bouts of weight cycling. Fluctuations in weight have been associated with worsened metabolic and cardiovascular outcomes; yet, the mechanisms explaining this potential correlation are not known. For determination of whether weight cycling modulates AT immune cell populations, inflammation, and insulin resistance, mice were subjected to a diet-switch protocol designed to induce weight cycling. Weight-cycled mice displayed decreased systemic glucose tolerance and impaired AT insulin sensitivity when compared with mice that gained weight but did not cycle. AT macrophage number and polarization were not modulated by weight cycling. However, weight cycling did increase the number of CD4(+) and CD8(+) T cells in AT. Expression of multiple T helper 1-associated cytokines was also elevated subsequent to weight cycling. Additionally, CD8(+) effector memory T cells were present in AT of both obese and weight-cycled mice. These studies indicate that an exaggerated adaptive immune response in AT may contribute to metabolic dysfunction during weight cycling.

  6. The signature of seeds in resurrection plants: a molecular and physiological comparison of desiccation tolerance in seeds and vegetative tissues.

    Science.gov (United States)

    Illing, Nicola; Denby, Katherine J; Collett, Helen; Shen, Arthur; Farrant, Jill M

    2005-11-01

    Desiccation-tolerance in vegetative tissues of angiosperms has a polyphyletic origin and could be due to 1) appropriation of the seed-specific program of gene expression that protects orthodox seeds against desiccation, and/or 2) a sustainable version of the abiotic stress response. We tested these hypotheses by comparing molecular and physiological data from the development of orthodox seeds, the response of desiccation-sensitive plants to abiotic stress, and the response of desiccation-tolerant plants to extreme water loss. Analysis of publicly-available gene expression data of 35 LEA proteins and 68 anti-oxidant enzymes in the desiccation-sensitive Arabidopsis thaliana identified 13 LEAs and 4 anti-oxidants exclusively expressed in seeds. Two (a LEA6 and 1-cys-peroxiredoxin) are not expressed in vegetative tissues in A. thaliana, but have orthologues that are specifically activated in desiccating leaves of Xerophyta humilis. A comparison of antioxidant enzyme activity in two desiccation-sensitive species of Eragrostis with the desiccation-tolerant E. nindensis showed equivalent responses upon initial dehydration, but activity was retained at low water content in E. nindensis only. We propose that these antioxidants are housekeeping enzymes and that they are protected from damage in the desiccation-tolerant species. Sucrose is considered an important protectant against desiccation in orthodox seeds, and we show that sucrose accumulates in drying leaves of E. nindensis, but not in the desiccation-sensitive Eragrostis species. The activation of "seed-specific" desiccation protection mechanisms (sucrose accumulation and expression of LEA6 and 1-cys-peroxiredoxin genes) in the vegetative tissues of desiccation-tolerant plants points towards acquisition of desiccation tolerance from seeds.

  7. Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects

    Directory of Open Access Journals (Sweden)

    Shen Z

    2017-07-01

    Full Text Available Zancong Shen,1 Michael Gillen,2 Jeffrey N Miner,1 Gail Bucci,1 David M Wilson,1 Jesse W Hall1 1Ardea Biosciences, Inc., San Diego, CA, 2AstraZeneca, Gaithersburg, MD, USA Purpose: Verinurad (RDEA3170 is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males.Subjects and methods: This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study. Panels of eight male subjects received a single oral dose of verinurad or placebo in either a fasted or fed state; panels of 10–12 male subjects received ascending doses of once-daily verinurad or placebo in a fasted state for 10 days. Serial blood and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse event (AE reports, laboratory tests, vital signs, and electrocardiograms (ECGs.Results: A total of 81 adult males completed the study. Following single doses of verinurad, maximum observed plasma concentration (Cmax and area under the plasma concentration–time curve (AUC increased in a dose-proportional manner; Cmax occurred at 0.5–0.75 hours and 1.25 hours in the fasted and fed states, respectively. Food decreased AUC by 23% and Cmax by 37%-53%. There was a modest accumulation of verinurad following multiple daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single dose and 61% (10 mg, multiple dose. The increase in urinary excretion of uric acid was greatest in the first 6 hours after dosing and was still evident ≥24 hours for verinurad doses ≥2 mg. Verinurad was well tolerated at all doses. No serious AEs, severe AEs, discontinuations due to AEs, or clinically significant laboratory or ECG abnormalities were reported.Conclusion: Single and multiple doses of verinurad were well tolerated

  8. Steady-state pharmacokinetics and tolerability of modafinil administered alone or in combination with dextroamphetamine in healthy volunteers.

    Science.gov (United States)

    Hellriegel, Edward T; Arora, Sanjay; Nelson, Michael; Robertson, Philmore

    2002-04-01

    The potential for a drug-drug interaction between modafinil and dextroamphetamine, each at steady state, was investigated in an open-label, randomized, single-period studyin 32 healthy male and female volunteers. All subjects received modafinil orally once daily for 28 days (200 mg on Days 1-7; 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received dextroamphetamine (20 mg) orally 7 hours after modafinil. Samples for pharmacokinetic (PK) profiling were obtained on Days 21 and 28. The mean changes in PK parameters for modafinil and its two circulating metabolites between the two groups were not statistically significantly different, except Cmax for modafinil acid. Adverse events obtained in the two groups were similar and mild or moderate in nature. The results indicate that administration of low-dose dextroamphetamine in this dosing regimen does not alter the steady-state pharmacokinetics of modafinil. The combination has a similar tolerability profile as modafinil alone.

  9. Prediction of drug distribution in subcutaneous xenografts of human tumor cell lines and healthy tissues in mouse: application of the tissue composition-based model to antineoplastic drugs.

    Science.gov (United States)

    Poulin, Patrick; Chen, Yung-Hsiang; Ding, Xiao; Gould, Stephen E; Hop, Cornelis Eca; Messick, Kirsten; Oeh, Jason; Liederer, Bianca M

    2015-04-01

    Advanced tissue composition-based models can predict the tissue-plasma partition coefficient (Kp ) values of drugs under in vivo conditions on the basis of in vitro and physiological input data. These models, however, focus on healthy tissues and do not incorporate data from tumors. The objective of this study was to apply a tissue composition-based model to six marketed antineoplastic drugs (docetaxel, DOC; doxorubicin, DOX; gemcitabine, GEM; methotrexate, MTX; topotecan, TOP; and fluorouracil, 5-FU) to predict their Kp values in three human tumor xenografts (HCT-116, H2122, and PC3) as well as in healthy tissues (brain, muscle, lung, and liver) under steady-state in vivo conditions in female NCR nude mice. The mechanisms considered in the tissue/tumor composition-based model are the binding to lipids and to plasma proteins, but the transporter effect was also investigated. The method consisted of analyzing tissue composition, performing the pharmacokinetics studies in mice, and calculating the corresponding in vivo Kp values. Analyses of tumor composition indicated that the tumor xenografts contained no or low amounts of common transporters by contrast to lipids. The predicted Kp values were within twofold and threefold of the measured values in 77% and 93% of cases, respectively. However, predictions for brain for each drug, for liver for MTX, and for each tumor xenograft for GEM were disparate from the observed values, and, therefore, not well served by the model. Overall, this study is the first step toward the mechanism-based prediction of Kp values of small molecules in healthy and tumor tissues in mouse when no transporter and permeation limitation effect is evident. This approach will be useful in selecting compounds based on their abilities to penetrate human cancer xenografts with a physiologically based pharmacokinetic (PBPK) model, thereby increasing therapeutic index for chemotherapy in oncology study. © 2015 Wiley Periodicals, Inc. and the American

  10. Antiseptic efficacy and tolerance of tissue-tolerable plasma compared with two wound antiseptics on artificially bacterially contaminated eyes from commercially slaughtered pigs.

    Science.gov (United States)

    Hammann, A; Huebner, N-O; Bender, C; Ekkernkamp, A; Hartmann, B; Hinz, P; Kindel, E; Koban, I; Koch, S; Kohlmann, T; Lademann, J; Matthes, R; Müller, G; Titze, R; Weltmann, K-D; Kramer, A

    2010-01-01

    To compare the tissue tolerance and efficacy of two wound antiseptics with tissue-tolerable plasma (TTP) on enucleated contaminated eyes from slaughtered pigs in order to draw consequences for the use of TTP on wounds. The corneas of extracted eyes were contaminated with Staphylococcus aureus or Pseudomonas aeruginosa. One and 10 min after application of 10% povidone (PVP)-iodine and 0.04% polyhexanide, respectively, the eyes were rinsed with inactivating solution. To test TTP, the plasma pen meandered over the eyes at a speed of 30 mm/s and a distance of 5 mm; the eyes were then rinsed with balanced salt solution. The reduction factor was calculated by the difference between the logarithm of colony-forming units in the rinse before and after antisepsis or TTP application. The efficacy of TTP (reduction factor 2.4-2.9) was significantly higher (p polyhexanide (reduction factor 1.7-2.1). TTP is more effective than the tested wound antiseptics. The lack of histological damage to the eyes of slaughtered pigs would seem to make its use as a wound antiseptic a viable alternative. In contrast to antiseptics, it supplies additional energy in the form of heat, electric fields and radicals by TTP. Copyright 2010 S. Karger AG, Basel.

  11. The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability.

    Science.gov (United States)

    Carhart-Harris, Robin L; Williams, Tim M; Sessa, Ben; Tyacke, Robin J; Rich, Ann S; Feilding, Amanda; Nutt, David J

    2011-11-01

    This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.

  12. Rate of Dehydration and Cumulative Desiccation Stress Interacted to Modulate Desiccation Tolerance of Recalcitrant Cocoa and Ginkgo Embryonic Tissues1

    Science.gov (United States)

    Liang, Yongheng; Sun, Wendell Q.

    2002-01-01

    Rate of dehydration greatly affects desiccation tolerance of recalcitrant seeds. This effect is presumably related to two different stress vectors: direct mechanical or physical stress because of the loss of water and physicochemical damage of tissues as a result of metabolic alterations during drying. The present study proposed a new theoretic approach to represent these two types of stresses and investigated how seed tissues responded differently to two stress vectors, using the models of isolated cocoa (Theobroma cacao) and ginkgo (Ginkgo biloba) embryonic tissues dehydrated under various drying conditions. This approach used the differential change in axis water potential (ΔΨ/Δt) to quantify rate of dehydration and the intensity of direct physical stress experienced by embryonic tissues during desiccation. Physicochemical effect of drying was expressed by cumulative desiccation stress [∫\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\pagestyle{empty} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}{\\mathrm{_{o}^{t}}}\\end{equation*}\\end{document}f(ψ,t)], a function of both the rate and time of dehydration. Rapid dehydration increased the sensitivity of embryonic tissues to desiccation as indicated by high critical water contents, below which desiccation damage occurred. Cumulative desiccation stress increased sharply under slow drying conditions, which was also detrimental to embryonic tissues. This quantitative analysis of the stress-time-response relationship helps to understand the physiological basis for the existence of an optimal dehydration rate, with which maximum desiccation tolerance could be achieved. The established numerical analysis model will prove valuable for the design of experiments that aim to elucidate biochemical and physiological mechanisms of desiccation tolerance. PMID:11950981

  13. Age-related intramyocardial patterns in healthy subjects evaluated with Doppler tissue imaging.

    Science.gov (United States)

    Pérez-David, Esther; García-Fernández, Miguel A; Ledesma, Maria Jesús; Malpica, Norberto; López Fernández, Teresa; Santos, Andrés; Moreno, Mar; Antoranz, José C; Bermejo, Javier; Desco, Manuel

    2005-06-01

    The aim of this study is to analyse spatial distribution of myocardial velocities (MV) and myocardial velocity gradient (MVG) with color M-mode Doppler tissue imaging (DTI) and to analyse the influence of age in such parameters. A prospective study including 66 healthy volunteers was carried out with color M-mode DTI. Postprocessing of images was performed using proprietary software allowing the division of the myocardial wall into subendocardium, mesocardium and subepicardium. MV corresponding to the three layers and MVG time curves were obtained and systolic, early diastolic and late diastolic peak values were identified. MV were highest in subendocardium in systole, protodiastole and telediastole compared to external layers. Protodiastolic peak MV decreased in all layers with age, but with a higher impact in the subendocardium (r = 0.72, b = 0.136 (IC 95% 0.107-0.164), p = 0.0005). Older age resulted in larger telediastolic peak MV, without significant differences among layers. Linear correlation between protodiastolic peak mitral flow and peak protodiastolic velocity was higher in endocardium than in other layers (r = 0.79, p = 0.0005). Color M-mode DTI multilayer analysis showed that endocardium is more susceptible to age-related changes involving diastolic function. This dependency on age should be considered when assessing MV in other clinical settings.

  14. Determination of time delay between blood and interstitial adipose tissue glucose concentration change by microdialysis in healthy volunteers

    NARCIS (Netherlands)

    Wientjes, KJC; Schoonen, AJM

    2001-01-01

    For the development and use of subcutaneous glucose sensors it is important to know the time lag between changes in blood glucose and subcutaneous interstitial glucose concentration. To determine the time lag we inserted a microdialysis probe into the abdominal subcutaneous adipose tissue of healthy

  15. Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects

    Directory of Open Access Journals (Sweden)

    Shin D

    2017-03-01

    Full Text Available Dongseong Shin,1 SeungHwan Lee,2 Sojeong Yi,2 Seo Hyun Yoon,2 Joo-Youn Cho,2 Mi Young Bahng,3 In-Jin Jang,2 Kyung-Sang Yu2 1Clinical Trials Center, Gachon University Gil Medical Center, Incheon, 2Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 3Department of Product Development, Dong-A ST, Seoul, Korea Objective: DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5 in the plasma and urine after administration of a single oral dose in healthy male subjects.Methods: A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP enzymes on the pharmacokinetics of DA-8031 was evaluated.Results: After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2–3 h and was eliminated with terminal elimination half-life of 17.9–28.7 h. The mean renal clearance was 3.7–5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20–80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized Cmax and AUC0–t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported.Conclusion: In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20

  16. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

    Science.gov (United States)

    Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

    2016-01-01

    Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin

  17. Cigarette smoking increases levels of retinol-binding protein-4 in healthy men with normal glucose tolerance

    Institute of Scientific and Technical Information of China (English)

    GAO Shan; WANG Yong-hui; LI Ming

    2012-01-01

    Background Smoking is related with insulin resistance and type 2 diabetes mellitus.Retinol-binding protein-4 is a new adipocytokine associated with insulin resistance.We investigated the serum levels of a series of adipocytokines including retinol-binding protein-4 in smokers and non-smokers to explore the possible roles of adipocytokines on smoking induced insulin resistance.Methods A total of 136 healthy male subjects (92 smokers and 44 non-smokers) with normal glucose tolerance were enrolled in the study.Adipocytokines including retinol-binding protein-4,visfatin,leptin,resistin,adiponectin were measured for the comparison between the two groups.Serum lipid profile,glucose,true insulin and proinsulin levels were measured as well in both groups.Food intake spectrum was also investigated.Results Both groups had similar profile of food consumption; visfatin,leptin,resistin and adiponectin,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,alanine aminotransferase,aspartate aminotransferase,as well as blood pressure and body mass index,were similar in both groups.Triglycerides,retinol-binding protein-4 and homeostatic model assessment index for insulin resistance were higher in smoker group ((2.58±2.53) vs.(1.60±0.94)mmol/L,(26.05±8.50) vs.(21.83±8.40) μg/ml,and 2.25±2.08 vs.1.58±1.15,respectively).Conclusion Smoking may have effect on insulin sensitivity,which is correlated with retinol-binding protein-4.

  18. Acute effects of light and dark roasted coffee on glucose tolerance: a randomized, controlled crossover trial in healthy volunteers.

    Science.gov (United States)

    Rakvaag, Elin; Dragsted, Lars Ove

    2016-10-01

    Epidemiological evidence suggests that coffee consumption is associated with a lower risk of type 2 diabetes. Coffee contains caffeine and several other components that may modulate glucose regulation. The chlorogenic acids (CGA) in coffee have been indicated as constituents that may help to normalize the acute glucose response after a carbohydrate challenge. The aim of this study was to investigate whether two coffee beverages that differ in CGA content due to different roasting degrees will differentially affect glucose regulation. In a controlled crossover trial, 11 healthy fasted volunteers consumed 300 mL of either light (LIR) or dark (DAR) roasted coffee, or water, followed 30 min later by a 75-g oral glucose tolerance test (OGTT). Blood samples were drawn at baseline, 30, 60, and 120 min. Differences in glucose and insulin responses and insulin sensitivity index (ISI) were analyzed. The CGA and caffeine contents in the coffees were analyzed using UPLC-MS/MS. No differences in glucose area under the curve (AUC) were found between treatments. Glucose concentrations were higher at 60 min after ingestion of DAR compared with water, while ingestion of LIR showed similar glucose concentrations as ingestion of water. Insulin AUC was higher after ingestion of DAR compared with water, and both coffees raised insulin concentrations and reduced ISI compared with water, with no difference between the two coffees. Two coffees with different CGA contents did not differentially affect glucose or insulin responses during an OGTT, but both increased the insulin response compared with water.

  19. Gene Expression Profiles in Paired Gingival Biopsies from Periodontitis-Affected and Healthy Tissues Revealed by Massively Parallel Sequencing

    Science.gov (United States)

    Båge, Tove; Lagervall, Maria; Jansson, Leif; Lundeberg, Joakim; Yucel-Lindberg, Tülay

    2012-01-01

    Periodontitis is a chronic inflammatory disease affecting the soft tissue and bone that surrounds the teeth. Despite extensive research, distinctive genes responsible for the disease have not been identified. The objective of this study was to elucidate transcriptome changes in periodontitis, by investigating gene expression profiles in gingival tissue obtained from periodontitis-affected and healthy gingiva from the same patient, using RNA-sequencing. Gingival biopsies were obtained from a disease-affected and a healthy site from each of 10 individuals diagnosed with periodontitis. Enrichment analysis performed among uniquely expressed genes for the periodontitis-affected and healthy tissues revealed several regulated pathways indicative of inflammation for the periodontitis-affected condition. Hierarchical clustering of the sequenced biopsies demonstrated clustering according to the degree of inflammation, as observed histologically in the biopsies, rather than clustering at the individual level. Among the top 50 upregulated genes in periodontitis-affected tissues, we investigated two genes which have not previously been demonstrated to be involved in periodontitis. These included interferon regulatory factor 4 and chemokine (C-C motif) ligand 18, which were also expressed at the protein level in gingival biopsies from patients with periodontitis. In conclusion, this study provides a first step towards a quantitative comprehensive insight into the transcriptome changes in periodontitis. We demonstrate for the first time site-specific local variation in gene expression profiles of periodontitis-affected and healthy tissues obtained from patients with periodontitis, using RNA-seq. Further, we have identified novel genes expressed in periodontitis tissues, which may constitute potential therapeutic targets for future treatment strategies of periodontitis. PMID:23029519

  20. A randomized, double-blind, placebo-controlled study to investigate the safety, tolerability, and pharmacokinetics of single enantiomer (+)-mefloquine compared with racemic mefloquine in healthy persons.

    Science.gov (United States)

    Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

    2010-12-01

    Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (-) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (-)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted.

  1. Comparison of breast cancer to healthy control tissue discovers novel markers with potential for prognosis and early detection.

    Science.gov (United States)

    Schummer, Michèl; Green, Ann; Beatty, J David; Karlan, Beth Y; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-02-09

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.

  2. Pyrosequencing revealed shifts of prokaryotic communities between healthy and disease-like tissues of the Red Sea sponge Crella cyathophora

    KAUST Repository

    Gao, Zhao-Ming

    2015-06-11

    Sponge diseases have been widely reported, yet the causal factors and major pathogenic microbes remain elusive. In this study, two individuals of the sponge Crella cyathophora in total that showed similar disease-like characteristics were collected from two different locations along the Red Sea coast separated by more than 30 kilometers. The disease-like parts of the two individuals were both covered by green surfaces, and the body size was much smaller compared with adjacent healthy regions. Here, using high-throughput pyrosequencing technology, we investigated the prokaryotic communities in healthy and disease-like sponge tissues as well as adjacent seawater. Microbes in healthy tissues belonged mainly to the Proteobacteria, Cyanobacteria and Bacteroidetes, and were much more diverse at the phylum level than reported previously. Interestingly, the disease-like tissues from the two sponge individuals underwent shifts of prokaryotic communities and were both enriched with a novel clade affiliated with the phylum Verrucomicrobia, implying its intimate connection with the disease-like Red Sea sponge C. cyathophora. Enrichment of the phylum Verrucomicrobia was also considered to be correlated with the presence of algae assemblages forming the green surface of the disease-like sponge tissues. This finding represents an interesting case of sponge disease and is valuable for further study.

  3. High-throughput sequencing approach uncovers the miRNome of peritoneal endometriotic lesions and adjacent healthy tissues.

    Directory of Open Access Journals (Sweden)

    Merli Saare

    Full Text Available Accumulating data have shown the involvement of microRNAs (miRNAs in endometriosis pathogenesis. In this study, we used a novel approach to determine the endometriotic lesion-specific miRNAs by high-throughput small RNA sequencing of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissues together with eutopic endometria of the same patients. We found five miRNAs specific to epithelial cells--miR-34c, miR-449a, miR-200a, miR-200b and miR-141 showing significantly higher expression in peritoneal endometriotic lesions compared to healthy peritoneal tissues. We also determined the expression levels of miR-200 family target genes E-cadherin, ZEB1 and ZEB2 and found that the expression level of E-cadherin was significantly higher in endometriotic lesions compared to healthy tissues. Further evaluation verified that studied miRNAs could be used as diagnostic markers for confirming the presence of endometrial cells in endometriotic lesion biopsy samples. Furthermore, we demonstrated that the miRNA profile of peritoneal endometriotic lesion biopsies is largely masked by the surrounding peritoneal tissue, challenging the discovery of an accurate lesion-specific miRNA profile. Taken together, our findings indicate that only particular miRNAs with a significantly higher expression in endometriotic cells can be detected from lesion biopsies, and can serve as diagnostic markers for endometriosis.

  4. High-Throughput Sequencing Approach Uncovers the miRNome of Peritoneal Endometriotic Lesions and Adjacent Healthy Tissues

    Science.gov (United States)

    Saare, Merli; Rekker, Kadri; Laisk-Podar, Triin; Sõritsa, Deniss; Roost, Anne Mari; Simm, Jaak; Velthut-Meikas, Agne; Samuel, Külli; Metsalu, Tauno; Karro, Helle; Sõritsa, Andrei; Salumets, Andres; Peters, Maire

    2014-01-01

    Accumulating data have shown the involvement of microRNAs (miRNAs) in endometriosis pathogenesis. In this study, we used a novel approach to determine the endometriotic lesion-specific miRNAs by high-throughput small RNA sequencing of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissues together with eutopic endometria of the same patients. We found five miRNAs specific to epithelial cells – miR-34c, miR-449a, miR-200a, miR-200b and miR-141 showing significantly higher expression in peritoneal endometriotic lesions compared to healthy peritoneal tissues. We also determined the expression levels of miR-200 family target genes E-cadherin, ZEB1 and ZEB2 and found that the expression level of E-cadherin was significantly higher in endometriotic lesions compared to healthy tissues. Further evaluation verified that studied miRNAs could be used as diagnostic markers for confirming the presence of endometrial cells in endometriotic lesion biopsy samples. Furthermore, we demonstrated that the miRNA profile of peritoneal endometriotic lesion biopsies is largely masked by the surrounding peritoneal tissue, challenging the discovery of an accurate lesion-specific miRNA profile. Taken together, our findings indicate that only particular miRNAs with a significantly higher expression in endometriotic cells can be detected from lesion biopsies, and can serve as diagnostic markers for endometriosis. PMID:25386850

  5. Sparing Healthy Tissue and Increasing Tumor Dose Using Bayesian Modeling of Geometric Uncertainties for Planning Target Volume Personalization

    Energy Technology Data Exchange (ETDEWEB)

    Herschtal, Alan, E-mail: Alan.Herschtal@petermac.org [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne (Australia); Te Marvelde, Luc [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Mengersen, Kerrie [School of Mathematical Sciences, Science and Engineering Faculty, Queensland University of Technology, Brisbane (Australia); Foroudi, Farshad [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Eade, Thomas [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Northern Clinical School, University of Sydney (Australia); Pham, Daniel [Department of Radiation Therapy, Peter MacCallum Cancer Centre, Melbourne (Australia); Caine, Hannah [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Kron, Tomas [The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne (Australia)

    2015-06-01

    Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predict future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes.

  6. Pyrosequencing revealed shifts of prokaryotic communities between healthy and disease-like tissues of the Red Sea sponge Crella cyathophora

    Directory of Open Access Journals (Sweden)

    Zhao-Ming Gao

    2015-06-01

    Full Text Available Sponge diseases have been widely reported, yet the causal factors and major pathogenic microbes remain elusive. In this study, two individuals of the sponge Crella cyathophora in total that showed similar disease-like characteristics were collected from two different locations along the Red Sea coast separated by more than 30 kilometers. The disease-like parts of the two individuals were both covered by green surfaces, and the body size was much smaller compared with adjacent healthy regions. Here, using high-throughput pyrosequencing technology, we investigated the prokaryotic communities in healthy and disease-like sponge tissues as well as adjacent seawater. Microbes in healthy tissues belonged mainly to the Proteobacteria, Cyanobacteria and Bacteroidetes, and were much more diverse at the phylum level than reported previously. Interestingly, the disease-like tissues from the two sponge individuals underwent shifts of prokaryotic communities and were both enriched with a novel clade affiliated with the phylum Verrucomicrobia, implying its intimate connection with the disease-like Red Sea sponge C. cyathophora. Enrichment of the phylum Verrucomicrobia was also considered to be correlated with the presence of algae assemblages forming the green surface of the disease-like sponge tissues. This finding represents an interesting case of sponge disease and is valuable for further study.

  7. Improved classification and visualization of healthy and pathological hard dental tissues by modeling specular reflections in NIR hyperspectral images

    Science.gov (United States)

    Usenik, Peter; Bürmen, Miran; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

    2012-03-01

    Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots, which are difficult to diagnose. Near-infrared (NIR) hyperspectral imaging is a new promising technique for early detection of demineralization which can classify healthy and pathological dental tissues. However, due to non-ideal illumination of the tooth surface the hyperspectral images can exhibit specular reflections, in particular around the edges and the ridges of the teeth. These reflections significantly affect the performance of automated classification and visualization methods. Cross polarized imaging setup can effectively remove the specular reflections, however is due to the complexity and other imaging setup limitations not always possible. In this paper, we propose an alternative approach based on modeling the specular reflections of hard dental tissues, which significantly improves the classification accuracy in the presence of specular reflections. The method was evaluated on five extracted human teeth with corresponding gold standard for 6 different healthy and pathological hard dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized regions. Principal component analysis (PCA) was used for multivariate local modeling of healthy and pathological dental tissues. The classification was performed by employing multiple discriminant analysis. Based on the obtained results we believe the proposed method can be considered as an effective alternative to the complex cross polarized imaging setups.

  8. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves; Dose de tolerance a l'irradiation des tissus sains: les nerfs peripheriques

    Energy Technology Data Exchange (ETDEWEB)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G. [Departement de radiotherapie, institut Bergonie, centre regional de lutte contre le cancer, 33 - Bordeaux (France); Huchet, A.; Mamou, N. [Service d' oncologie medicale et de radiotherapie, CHU Saint-Andre, 33 - Bordeaux (France); Loiseau, H. [Service de neurochirurgie, CHU Pellegrin, 33 - Bordeaux (France)

    2010-07-15

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  9. Fluorescent marker-based and marker-free discrimination between healthy and cancerous human tissues using hyper-spectral imaging

    Science.gov (United States)

    Arnold, Thomas; De Biasio, Martin; Leitner, Raimund

    2015-06-01

    Two problems are addressed in this paper (i) the fluorescent marker-based and the (ii) marker-free discrimination between healthy and cancerous human tissues. For both applications the performance of hyper-spectral methods are quantified. Fluorescent marker-based tissue classification uses a number of fluorescent markers to dye specific parts of a human cell. The challenge is that the emission spectra of the fluorescent dyes overlap considerably. They are, furthermore disturbed by the inherent auto-fluorescence of human tissue. This results in ambiguities and decreased image contrast causing difficulties for the treatment decision. The higher spectral resolution introduced by tunable-filter-based spectral imaging in combination with spectral unmixing techniques results in an improvement of the image contrast and therefore more reliable information for the physician to choose the treatment decision. Marker-free tissue classification is based solely on the subtle spectral features of human tissue without the use of artificial markers. The challenge in this case is that the spectral differences between healthy and cancerous tissues are subtle and embedded in intra- and inter-patient variations of these features. The contributions of this paper are (i) the evaluation of hyper-spectral imaging in combination with spectral unmixing techniques for fluorescence marker-based tissue classification, (ii) the evaluation of spectral imaging for marker-free intra surgery tissue classification. Within this paper, we consider real hyper-spectral fluorescence and endoscopy data sets to emphasize the practical capability of the proposed methods. It is shown that the combination of spectral imaging with multivariate statistical methods can improve the sensitivity and specificity of the detection and the staging of cancerous tissues compared to standard procedures.

  10. Potassium retention in leaf mesophyll as an element of salinity tissue tolerance in halophytes.

    Science.gov (United States)

    Percey, William J; Shabala, Lana; Wu, Qi; Su, Nana; Breadmore, Michael C; Guijt, Rosanne M; Bose, Jayakumar; Shabala, Sergey

    2016-12-01

    Soil salinity remains a major threat to global food security, and the progress in crop breeding for salinity stress tolerance may be achieved only by pyramiding key traits mediating plant adaptive responses to high amounts of dissolved salts in the rhizosphere. This task may be facilitated by studying natural variation in salinity tolerance among plant species and, specifically, exploring mechanisms of salinity tolerance in halophytes. The aim of this work was to establish the causal link between mesophyll ion transport activity and plant salt tolerance in a range of evolutionary contrasting halophyte and glycophyte species. Plants were grown under saline conditions in a glasshouse, followed by assessing their growth and photosynthetic performance. In a parallel set of experiments, net K(+) and H(+) transport across leaf mesophyll and their modulation by light were studied in control and salt-treated mesophyll segments using vibrating non-invasive ion selective microelectrode (the MIFE) technique. The reported results show that mesophyll cells in glycophyte species loses 2-6 fold more K(+) compared with their halophyte counterparts. This decline was reflected in a reduced maximum photochemical efficiency of photosystem II, chlorophyll content and growth observed in the glasshouse experiments. In addition to reduced K(+) efflux, the more tolerant species also exhibited reduced H(+) efflux, which is interpreted as an energy-saving strategy allowing more resources to be redirected towards plant growth. It is concluded that the ability of mesophyll to retain K(+) without a need to activate plasma membrane H(+)-ATPase is an essential component of salinity tolerance in halophytes and halophytic crop plants.

  11. CHANGES IN TOOTH HARD TISSUE MINERALI-ZATION AND BLOOD RHEOLOGY IN HEALTHY ADOLESCENTS AND THOSE WITH THYROID DYSFUNCTION.

    Science.gov (United States)

    Beriashvili, S; Nikolaishvili, M; Mantskava, M; Momtsemlidze, N; Franchuk, K

    2016-11-01

    Thyroid dysfunction causes spreading and development of caries in the teeth and changes in periodontal tissues. In addition, it causes changes in peripheral blood flow and mineralization, local transcapillary metabolism causes changes in blood rheology. There are only few works in this direction and, therefore, the purpose of our research was to find out how the mineralization and the rheological properties of blood are changed in lesion of periodontal tissue on a background of thyroid dysfunction. Accordingly, the stomatological study was conducted in 75 adolescents aged 12-18 years by the standard method, recommended by the World Health Organization. According to the study, 45 patients out of them suffered from thyroid dysfunction, in particular from hypothyroidism. The comparator group consisted of 30 children of the same age without endocrine abnormalities. By the gained results it is noted that in spite of different type lesions due to dental caries, the caries incidence and intensiveness is higher in children with hypothyroidism as compared to healthy children. Decrease in saliva excretion rate and increase in oral fluid viscosity was found in children with thyroid and endocrine diseases as compared to healthy children. In children with endocrine disorders concurrent increase in calcium content (1,43±0,08 mmol/l) and decrease in inorganic phosphate concentrations (4,54±0,15 mmol/l) is reliably established. In children with thyroid disfunction and while periodontal tissue pathology, rheological features are disordered more dramatically than in healthy children. Therefore, it can be said that the changes in the adolescents' thyroid function is one of the reasons for formation of periodontal tissue diseases.Therefore, at detecting even the first signs of the periodontal tissue diseases, it is desirable in adolescents to assess the thyroid functional condition, since it will be the precondition for effective treatment and management of dental disease, in

  12. Automated classification and visualization of healthy and pathological dental tissues based on near-infrared hyper-spectral imaging

    Science.gov (United States)

    Usenik, Peter; Bürmen, Miran; Vrtovec, Tomaž; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

    2011-03-01

    Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots which are difficult to diagnose. If detected early enough, such demineralization can be arrested and reversed by non-surgical means through well established dental treatments (fluoride therapy, anti-bacterial therapy, low intensity laser irradiation). Near-infrared (NIR) hyper-spectral imaging is a new promising technique for early detection of demineralization based on distinct spectral features of healthy and pathological dental tissues. In this study, we apply NIR hyper-spectral imaging to classify and visualize healthy and pathological dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized areas. For this purpose, a standardized teeth database was constructed consisting of 12 extracted human teeth with different degrees of natural dental lesions imaged by NIR hyper-spectral system, X-ray and digital color camera. The color and X-ray images of teeth were presented to a clinical expert for localization and classification of the dental tissues, thereby obtaining the gold standard. Principal component analysis was used for multivariate local modeling of healthy and pathological dental tissues. Finally, the dental tissues were classified by employing multiple discriminant analysis. High agreement was observed between the resulting classification and the gold standard with the classification sensitivity and specificity exceeding 85 % and 97 %, respectively. This study demonstrates that NIR hyper-spectral imaging has considerable diagnostic potential for imaging hard dental tissues.

  13. Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective.

    Science.gov (United States)

    Demetris, Anthony J; Lunz, John G; Randhawa, Parmjeet; Wu, Tong; Nalesnik, Michael; Thomson, Angus W

    2009-01-01

    Several factors acting together have recently enabled clinicians to seriously consider whether chronic immunosuppression is needed in all solid organ allograft recipients. This has prompted a dozen or so centers throughout the world to prospectively wean immunosuppression from conventionally treated liver allograft recipients. The goal is to lessen the impact of chronic immunosuppression and empirically identify occasional recipients who show operational tolerance, defined as gross phenotype of tolerance in the presence of an immune response and/or immune deficit that has little or no significant clinical impact. Rare operationally tolerant kidney allograft recipients have also been identified, usually by single case reports, but only a couple of prospective weaning trials in conventionally treated kidney allograft recipients have been attempted and reported. Pre- and postweaning allograft biopsy monitoring of recipients adds a critical dimension to these trials, not only for patient safety but also for determining whether events in the allografts can contribute to a mechanistic understanding of allograft acceptance. The following is based on a literature review and personal experience regarding the practical and scientific aspects of biopsy monitoring of potential or actual operationally tolerant human liver and kidney allograft recipients where the goal, intended or attained, was complete withdrawal of immunosuppression.

  14. Laser scanning microscopy as a means to assess the augmentation of tissue repair by exposition of wounds to tissue tolerable plasma

    Science.gov (United States)

    Vandersee, Staffan; Richter, Heike; Lademann, Jürgen; Beyer, Marc; Kramer, Axel; Knorr, Fanny; Lange-Asschenfeldt, Bernhard

    2014-11-01

    Confocal laser scan microscopy (CLSM) has emerged as a tool for in vivo assessment of cutaneous conditions. In particular, its use in wound healing assessment has increasingly moved into focus. In this context, the application of tissue tolerable plasma (TTP) for wound treatment has recently become one of the most innovative therapeutic modalities. We analyzed wound healing parameters such as area decline and histomorphological characteristics of tissue repair in six subjects with vacuum-generated wounds on the forearm with a four-armed design: (A) no treatment, (B) treatment with TTP, (C) treatment with octenidine, and (D) sequential treatment with TTP and octenidine. Assessment of the wounds was conducted during six visits over the course of two weeks. The wounds were analyzed by photography and CLSM. TTP treatment led to a more rapid area decline that was statistically significant in comparison to other treatment groups. Besides mild pain, it was well tolerated. Morphologically, wound healing was found to initiate from the edges with the formation of dendritic structures consisting of keratinocytes. CLSM is a valuable tool for assessing the dynamics of wound healing. TTP, for reasons that still need to be investigated, can accelerate wound repair.

  15. A randomized dose-escalation study to assess the safety, tolerability, and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers.

    Science.gov (United States)

    Ogama, Yoichiro; Mineyama, Tomoko; Yamamoto, Asuka; Woo, Margaret; Shimada, Naomi; Amagasaki, Taro; Natsume, Kazuto

    2013-03-01

    Ruxolitinib (INC424), a potent and selective oral Janus kinase 1 and 2 inhibitor, was recently approved by the US food and drug administration for the treatment of intermediate or high-risk myelofibrosis. The safety, tolerability, and pharmacokinetics (PK) of ruxolitinib have been extensively evaluated in healthy subjects and patients. The present study is the first to investigate the PK and tolerability of ruxolitinib in the Japanese population. Forty subjects were randomized to receive single (10-100 mg) and multiple (10 and 25 mg every 12 h) doses of ruxolitinib or placebo. Cohorts were sequentially enrolled based on the outcome of safety assessments. Ruxolitinib was rapidly absorbed, and its exposure increased dose proportionally up to 100 mg. The half-life of ruxolitinib was approximately 3 h, and drug accumulation was not observed after repeated dosing at a 12-h dosing interval. Decreasing absolute neutrophil counts were observed in five Japanese subjects treated once (100 mg, n = 1) or twice (10 mg, n = 3; 25 mg, n = 1) daily. These events were manageable and reversible upon drug discontinuation. Orally administered ruxolitinib was well tolerated in healthy Japanese volunteers. There were no apparent differences in the safety or PK of ruxolitinib between Japanese and non-Japanese subjects.

  16. Supplementation of the diet with the functional fiber PolyGlycoplex® is well tolerated by healthy subjects in a clinical trial

    Directory of Open Access Journals (Sweden)

    Wood Simon

    2009-02-01

    Full Text Available Abstract Background The relationship of dietary fiber to overall health is of great importance, as beneficial effects have been demonstrated with the use of fiber from diverse sources, some traditional, other novel. PolyGlycopleX® (PGX® is a unique proprietary product composed of three water-soluble polysaccharides, that when processed using novel technology give rise to a final product – a soluble, highly viscous functional fiber. Methods Because of its potential use in food and dietary supplements, a randomized, double-blind, placebo controlled clinical study was conducted to evaluate the tolerance to PGX ingestion for 21 days, to a maximum dose level of 10 g per day, in healthy male and female volunteers. The main objective of the study was to evaluate the overall gastrointestinal (GI tolerance, while secondary objectives were to evaluate possible changes in hematological, biochemical, urinary and fecal parameters. Results Results show that PGX is well tolerated as part of a regular diet with only mild to moderate adverse effects, similar to those seen with a moderate intake of dietary fiber in general, and fruits and vegetables. Because PGX is a highly viscous, functional fiber, it also demonstrates several physiological responses including, but not limited to maintaining healthy total and LDL cholesterol and uric acid levels.

  17. Tolerance to low temperatures of Toxocara cati larvae in chicken muscle tissue

    DEFF Research Database (Denmark)

    Taira, Kensuke; Saitoh, Yasuhide; Okada, Natsuki;

    2012-01-01

    Infectivity of Toxocara cati larvae in muscle tissue of chickens after storage at 4 degrees C and -25 degrees C was assessed in a mouse bioassay to provide information on the risk of meat-borne toxocarosis. Muscle tissue samples of 30-day old T. cati infections were stored at 4 degrees C for 14...

  18. Tissue Damage Markers after a Spinal Manipulation in Healthy Subjects: A Preliminary Report of a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    A. Achalandabaso

    2014-01-01

    Full Text Available Spinal manipulation (SM is a manual therapy technique frequently applied to treat musculoskeletal disorders because of its analgesic effects. It is defined by a manual procedure involving a directed impulse to move a joint past its physiologic range of movement (ROM. In this sense, to exceed the physiologic ROM of a joint could trigger tissue damage, which might represent an adverse effect associated with spinal manipulation. The present work tries to explore the presence of tissue damage associated with SM through the damage markers analysis. Thirty healthy subjects recruited at the University of Jaén were submitted to a placebo SM (control group; n=10, a single lower cervical manipulation (cervical group; n=10, and a thoracic manipulation (n=10. Before the intervention, blood samples were extracted and centrifuged to obtain plasma and serum. The procedure was repeated right after the intervention and two hours after the intervention. Tissue damage markers creatine phosphokinase (CPK, lactate dehydrogenase (LDH, C-reactive protein (CRP, troponin-I, myoglobin, neuron-specific enolase (NSE, and aldolase were determined in samples. Statistical analysis was performed through a 3×3 mixed-model ANOVA. Neither cervical manipulation nor thoracic manipulation did produce significant changes in the CPK, LDH, CRP, troponin-I, myoglobin, NSE, or aldolase blood levels. Our data suggest that the mechanical strain produced by SM seems to be innocuous to the joints and surrounding tissues in healthy subjects.

  19. Mapping of healthy oral mucosal tissue using diffuse reflectance spectroscopy: ratiometric-based total hemoglobin comparative study.

    Science.gov (United States)

    Hafez, Razan; Hamadah, Omar; Bachir, Wesam

    2015-11-01

    The objective of this study is to clinically evaluate the diffuse reflectance spectroscopy (DRS) ratiometric method for differentiation of normal oral mucosal tissues with different histological natures and vascularizations in the oral cavity. Twenty-one healthy patients aged 20-44 years were diagnosed as healthy and probed with a portable DRS system. Diffuse reflectance spectra were recorded in vivo in the range (450-650 nm). In this study, the following three oral mucosal tissues were considered: masticatory mucosa, lining mucosa, and specialized mucosa. Spectral features based on spectral intensity ratios were determined at five specific wavelengths (512, 540, 558, 575, and 620 nm). Total hemoglobin based on spectral ratios for the three anatomical regions have also been evaluated. The three studied groups representing different anatomical regions in the oral cavity were compared using analysis of variance and post hoc least significant difference tests. Statistical analysis showed a significant difference in the mean of diffuse spectral ratios between the groups (P spectroscopy might be used for creating a DRS databank of normal oral mucosal tissue with specific spectral ratios featuring the total hemoglobin concentrations. That would further enhance the discrimination of oral tissue for examining the histological nature of oral mucosa and diagnosis of early precancerous changes in the oral cavity based on non-invasive monitoring of neovascularization.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  1. WJD 5th Anniversary Special Issues(1): Insulin Benefits of healthy adipose tissue in the treatment of diabetes

    Institute of Scientific and Technical Information of China (English)

    Subhadra; C; Gunawardana

    2014-01-01

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin.Insulin deficiency is either absolute due to destruction or failure of pancreaticβcells,or relative due to decreased sensitivity of peripheral tissues to insulin.The primary lesion being related to insulin,treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin.These therapies have their own limitations and complications,some of which can be life-threatening.For example,exogenous insulin administration can lead to fatal hypoglycemic episodes;islet/pancreas transplantation requires life-long immunosuppressive therapy;and anti-diabetic drugs have dangerous side effects including edema,heart failure and lactic acidosis.Thus the need remains for better safer long term treatments for diabetes.The ultimate goal in treating diabetes is to re-establish glucose homeostasis,preferably through endogenously generated hormones.Recent studies increasingly show that extra-pancreatic hormones,particularly those arising from adipose tissue,can compensate for insulin,or entirely replace the function of insulin under appropriate circumstances.Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism.While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines,healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties,which can complement and/or compensate for the function of insulin.Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes,and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin.Although specific adipokines may correct diabetes,administration of individual adipokines still carries risks similar to those of insulin monotherapy.Thus a better approach is to

  2. Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo‐Controlled Studies in Healthy Volunteers

    Science.gov (United States)

    Vets, Eva; Gheyle, Lien; Osuntokun, Wande; Larbig, Michael; Neelakantham, Srikanth; Sandham, David; Dubois, Gerald; Elbast, Walid; Goldsmith, Paul; Weiss, Markus

    2016-01-01

    Abstract We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1‒3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2, ∼20 hours). Steady state was achieved in 4 days with fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day. No dose‐dependent adverse events were observed, and all the events were mild or moderate in severity. Systemic concentrations were sufficiently high to achieve relevant target occupancy, considering in vitro pharmacology data. In summary, the data support further development as a once‐daily oral therapy for allergic diseases. PMID:27310331

  3. Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers.

    Science.gov (United States)

    Erpenbeck, Veit J; Vets, Eva; Gheyle, Lien; Osuntokun, Wande; Larbig, Michael; Neelakantham, Srikanth; Sandham, David; Dubois, Gerald; Elbast, Walid; Goldsmith, Paul; Weiss, Markus

    2016-07-01

    We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1-3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2 , ∼20 hours). Steady state was achieved in 4 days with fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day. No dose-dependent adverse events were observed, and all the events were mild or moderate in severity. Systemic concentrations were sufficiently high to achieve relevant target occupancy, considering in vitro pharmacology data. In summary, the data support further development as a once-daily oral therapy for allergic diseases.

  4. Microdialysis of glucose in subcutaneous adipose tissue up to 3 weeks in healthy volunteers

    NARCIS (Netherlands)

    Wientjes, K.J C; Vonk, P; Vonk-van Klei, Y; Schoonen, A.J M; Kossen, N.W F

    1998-01-01

    OBJECTIVE - To measure possible changes in dialysate glucose concentrations over time, to validate the diffusional model for glucose transport from tissue to the probe, and to evaluate the actual glucose concentration in adipose tissue. RESEARCH DESIGN AND METHODS - Glucose concentrations in the sub

  5. LR8 Expression in fibroblasts of healthy and fibrotic human tissues.

    Science.gov (United States)

    Etikala, Anusha; Bruce, Greg; Hudkins, Kelly; Narayanan, A S

    2017-07-01

    LR8 gene was first reported in a subpopulation of cultured human lung fibroblasts expressing the receptor for C1q-globular domain, and it was not detectable in cultured endothelial cells and smooth muscle cells. LR8 mRNA levels were higher in fibrotic lungs. In this study we assessed LR8 production in human tissues and determined if the distribution of fibroblasts producing LR8 is affected in fibrosis. Normal and fibrotic tissue sections from human liver, lung and kidneys were immunostained with antibodies to LR8 and examined for the presence of fibroblasts staining positively and negatively. The cells were also examined for co-expression of α-smooth muscle actin (SMA), a marker for myofibroblasts. The results showed that LR8 was expressed by fibroblasts, smooth muscle cells, endothelial cells, bile duct cells, pulmonary alveolar cells and distal and proximal kidney tubule cells. Connective tissues of normal and fibrotic tissues contained fibroblasts staining positively and negatively with anti- LR8 antibody. The number of LR8-positive cells was higher in fibrotic tissues, but differences were not statistically significant. Fibroblasts producing both LR8 and SMA were present in higher numbers in fibrotic tissues as compared to normal tissues and the differences were statistically significant (phuman tissues, and that in fibrotic tissues cells co-expressing LR8 and SMA are present. Our results indicate that LR8 expressing cells may participate in the early stages of fibrotic diseases and that fibroblasts expressing LR8, not LR8 negative cells, have potential to become myofibroblasts in fibrotic tissues.

  6. Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis)

    Science.gov (United States)

    Honeyfield, D.C.; Ross, J.P.; Carbonneau, D.A.; Terrell, S.P.; Woodward, A.R.; Schoeb, T.R.; Perceval, H.F.; Hinterkopf, J.P.

    2008-01-01

    An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B"1) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. ?? Wildlife Disease Association 2008.

  7. Feasibility, tolerability and safety of pediatric hyperpolarized {sup 129}Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Walkup, Laura L.; Watters, Erin; Ruppert, Kai [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Thomen, Robert P.; Woods, Jason C. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Washington University in St. Louis, Department of Physics, St. Louis, MO (United States); Akinyi, Teckla G.; Cleveland, Zackary I. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH (United States); Clancy, John P. [Cincinnati Children' s Hospital Medical Center, Division of Pulmonary Medicine, Cincinnati, OH (United States)

    2016-11-15

    Hyperpolarized {sup 129}Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized {sup 129}Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent {sup 129}Xe MRI, receiving up to three doses of {sup 129}Xe gas prepared by either a commercially available or a homebuilt {sup 129}Xe polarizer. Subject heart rate and SpO{sub 2} were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of {sup 129}Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO{sub 2} (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO{sub 2} values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following {sup 129}Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of {sup 129}Xe MRI has been assessed in a small group of children as young as 6 years. SpO{sub 2} changes were consistent with the expected physiological effects of a short anoxic breath

  8. Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome

    DEFF Research Database (Denmark)

    Leder, Lena; Kolehmainen, Marjukka; Narverud, Ingunn

    2016-01-01

    BACKGROUND: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism......-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. METHODS: A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study...

  9. The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects

    DEFF Research Database (Denmark)

    Rhee, Nicolai Alexander; Østoft, Signe Harring; Holst, Jens Juul

    2014-01-01

    /mol [5.3±0.1%]) were randomised to two paired study days comprising a 4h 50 g-OGTT with paracetamol (A) and an isoglycaemic i.v. glucose infusion (IIGI) (B), with (A1+B1) and without (A2+B2) preceding administration of the DPP-4 inhibitor sitagliptin. Results Isoglycaemia was obtained in all subjects...... gastric emptying (Tmax for plasma paracetamol: 86±9 vs 80±12 min, p=0.60) changed following DPP-4 inhibition. Conclusions These results suggest that acute increases in active incretin hormone levels do not affect glucose tolerance, GIGD, incretin effect, glucagon responses or gastric emptying in healthy...

  10. The expression of syndecan-1, syndecan-4 and decorin in healthy human breast tissue during the menstrual cycle

    Directory of Open Access Journals (Sweden)

    Naessén Tord

    2010-04-01

    Full Text Available Abstract Background In order to unravel the interactions between the epithelium and the extra cellular matrix (ECM in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle. Methods Tissue from healthy women undergoing breast reduction plastic surgery was examined using immunohistochemistry (n = 38 and Real-Time RT-PCR (n = 20. Both parous and nulliparous women were eligible and the mean age of the women was 34(+/- 10 years with regular menstrual cycles (28 +/- 7 days. None of the women had used hormonal treatment the last three months. The women were randomized to needle biopsy two months before the operation in the follicular or luteal menstrual phase and for another biopsy at the operation in the opposite phase. Serum samples were obtained to characterize the menstrual phase. The Wilcoxon signed rank test and Mann Whitney test were used for statistical analyses. Results By real time-RT-PCR the gene signal for all three proteoglycans; decorin (p = 0.02 and syndecan-1 (p = 0.03 and syndecan-4 (p = 0.02 was significantly lower among parous women in the luteal phase than in the follicular phase. Immunohistochemistry confirmed the identification of the proteins but no significant difference between menstrual phases was observed. Serum samples verified the menstrual phase. Conclusions Our study shows, for the first time in the

  11. Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancys.

    Science.gov (United States)

    Huda, Shahzya S; Jordan, Fiona; Bray, Jack; Love, Gillian; Payne, Reba; Sattar, Naveed; Freeman, Dilys J

    2017-07-01

    Obesity increases pre-eclampsia (PE) risk. Adipose tissue inflammation may contribute to the clinical syndrome of PE. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in PE and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and PE (n=13) mothers. Basal and lipopolysaccharide (LPS) stimulated adipocyte TNFα, IL-6, CCL-2, and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In PE only, visceral adipose tissue TNFα release was increased after LPS stimulation (57 [76] versus 81 [97] pg/ml/µg DNA, P=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r = -0.61, P=0.030) in PE. Visceral adipocyte IL-6 release was increased after LPS stimulation in PE only (566 [696] versus 852 [914] pg/ml/µg DNA, P=0.019). Visceral adipocyte CCL-2 basal (67 [61] versus 187 [219] pg/ml/µgDNA, P=0.049) and stimulated (46 [46] versus 224 [271] pg/ml/µg DNA, P=0.003) release was greater than in subcutaneous adipocytes in PE only. In PE, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] versus 0.8 [0.00-1.27] TNF/PPIA ratio, P=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] versus 51.0[29.9] CSF1R/PPIA ratio, P=0.011) and activated (cfms+) macrophage count (6.7[2.6] versus 15.2[8.8] % cfms+/adipocyte, P=0.031) were higher in PE than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in PE. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with PE. © 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution

  12. Left ventricular radial colour and longitudinal pulsed-wave tissue Doppler echocardiography in 39 healthy domestic pet rabbits.

    Science.gov (United States)

    Casamian-Sorrosal, Domingo; Saunders, Richard; Browne, William; Elliot, Sarah; Fonfara, Sonja

    2014-10-01

    This paper reports radial colour and longitudinal mitral annulus pulsed-wave tissue Doppler findings in a large cohort of healthy, adult pet rabbits. Thirty-nine rabbits (22 Dwarf Lops, 14 French Lops and three Alaskans) underwent conscious echocardiography. The median age of the rabbits was 22 months and the median weight was 2.8 kg (Dwarf Lop 2.4 kg/French Lop 6.0 kg). Adequate radial colour and longitudinal pulsed-wave tissue Doppler traces were obtained in 100% and 85% of cases, respectively. Most systolic tissue Doppler parameters were significantly higher in French Lops than in Dwarf Lops. Separation of mitral inflow diastolic waves was present in 40% of cases using conventional spectral Doppler and in >60% of cases using pulsed-wave tissue Doppler which could be beneficial when evaluating diastolic function in rabbits. This study can be used as a reference for normal echocardiographic tissue Doppler values for adult rabbits undergoing conscious echocardiography in clinical practice.

  13. Tolerance and Safety Evaluation in a Large Cohort of Healthy Infants Fed an Innovative Prebiotic Formula : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Piemontese, Pasqua; Gianni, Maria L.; Braegger, Christian P.; Chirico, Gaetano; Grueber, Christoph; Riedler, Josef; Arslanoglu, Sertac; van Stuijvenberg, Margriet; Boehm, Guenther; Jelinek, Juergen; Roggero, Paola

    2011-01-01

    Background: the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk. The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy. Methodology/Principal F

  14. Quantification of tissue inhibitor of metalloproteinases 2 in plasma from healthy donors and cancer patients

    DEFF Research Database (Denmark)

    Larsen, M. B.; Stephens, R. W.; Brünner, Nils;

    2005-01-01

    and optimized for measurement of TIMP-2 in plasma. The capturing antibody in the ELISA was a monoclonal, while the detecting antibody was a chicken polyclonal antibody recognizing the native form of human TIMP-2. The levels of TIMP-2 were measured in ethylenediaminetetraacetic acid (EDTA) and citrate plasma...... from healthy donors. The median values were determined as 163 ng/ml (n = 186) with a range of 109-253 ng/ml for EDTA plasma and 139 ng/ml (n = 77) with a range of 95-223 ng/ml for citrate plasma. The TIMP-2 concentration in citrate plasma from 15 patients with advanced, stage IV breast cancer had...... a median value of 160 ng/ml, only slightly higher but statistically distinguishable from the level found in citrate plasma from the healthy donors. In addition, the TIMP-2 concentration in EDTA plasma from colorectal cancer patients revealed a significantly higher level in plasma from patients with Dukes...

  15. Physiological performance and differential expression profiling of genes associated with drought tolerance in root tissue of four contrasting varieties of two Gossypium species.

    Science.gov (United States)

    Singh, Ruchi; Pandey, Neha; Kumar, Anil; Shirke, Pramod A

    2016-01-01

    Root growth in drying soil is generally limited by a combination of mechanical impedance and water stress. As the major function of root tissue is water and nutrient uptake, so it imparts an important role in plant growth and stress management. Previously, we have studied physiological performance and expression profiling of gene associated with drought tolerance in leaf tissue of four cotton varieties. Here, we have further continued our studies with the root tissue of these varieties. The Gossypium hirsutum species JKC-770 is drought-tolerant and KC-2 is drought-sensitive, while Gossypium herbaceum species JKC-717 is drought-tolerant and RAHS-187 is drought-sensitive. JKC-770 and JKC-717 the drought-tolerant varieties showed a comparatively high glutathione-S-transferase, superoxide dismutase, proline along with their gene expression, and low malondialdehyde content indicating low membrane damage and better antioxidative defense under drought condition. The expression levels of cellulose synthase, xyloglucan:xyloglucosyl transferase, and glycosyl hydrolases suggest modulation in cell wall structure and partitioning of sugars towards osmoprotectants instead of cell wall biosynthesis in tolerant varieties. Heat shock proteins and serine/threonine protein phosphotases show upregulation under drought condition, which are responsible for temperature tolerance and protein phosphorylation, respectively. These effects many metabolic processes and may be playing a key role in drought tolerance and adaptability of JKC-770 towards drought tolerance. The long-term water use efficiency (WUE) estimated in terms of carbon isotope discrimination (∆(13)C) in the root tissues showed maximum depletion in the ∆(13)C values in JKC-770 variety, while minimum in RAHS-187 under drought stress with reference to their respective control, suggesting a high WUE in JKC-770 variety.

  16. Multi-elemental analysis of brain tissue from healthy Wistar rats using sector field inductively coupled plasma mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Paul, Mitchell C. [Molecular Structure and Detection Group, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan NSW 2308 (Australia); Parsons, Carl H. [School of Biomedical Science, University of Newcastle, Callaghan NSW 2308 (Australia); Calford, Mike B. [School of Biomedical Science, University of Newcastle, Callaghan NSW 2308 (Australia); Nagy-Felsobuki, Ellak I. von [Molecular Structure and Detection Group, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan NSW 2308 (Australia)]. E-mail: ellak@newcastle.edu.au

    2004-09-20

    The normal distribution of a range of elements in the brain tissue of healthy Wistar rats was established using sector field inductively coupled plasma mass spectrometry. A protocol was developed to determine concentrations of Ag, Cd, Hg, Pb, Bi, U, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As and Se in specific brain regions. The concentrations of these elements were determined in the range of 2{+-}1 (e.g. Cr in diencephalon) to 7558{+-}450 ng ml{sup -1} (e.g. Fe in olfactory bulb). The detection limits of the sixteen elements ranged between 5 and 300 pg ml{sup -1}, with U yielding the lowest and Fe the highest value. The validity of the protocol was assessed by the analysis of SRM 1577B Bovine Liver and brain tissue spike recoveries. A principal component analysis was used to reveal elemental patterns of the brain regions.

  17. Photoacoustic characterization of the left atrium wall: healthy and ablated tissue (Conference Presentation)

    Science.gov (United States)

    Iskander-Rizk, Sophinese; Kruizinga, Pieter; van der Steen, Antonius F. W.; van Soest, Gijs

    2017-03-01

    Radio-frequency ablation (RFA) creates a thermal lesion in the atrial wall, with clearly recognizable optical and structural changes to the tissue. This can be detected by photoacoustic (PA) imaging, and used for monitoring of lesion depth, lesion functionality, and limiting excessive ablation. Porcine left atrium tissue can be split into three visually distinguishable regions, a thick white endocardium, pinkish myocardium and a thin gelatinous epicardium. In this study, we characterize the layered left atrium tissue in terms of the relevant photoacoustic parameters (wavelength, frequency content, imaging depth, lesion contrast). Previous studies in the literature targeted the photoacoustic characterization of fresh and ablated ventricular myocardium in the range of 650nm to 900nm. In this study we target the characterization of fresh and ablated left atrial tissue from 410nm to 1000nm, including the endocardium and epicardium. We generate the photoacoustic signals using a tunable pulsed laser source, and record those signals using either a broadband 1 mm hydrophone or a L12-3v transducer connected to the Verasonics machine for more realistic conditions. Initial experiments on fresh porcine tissue show that the presence of the endocardium and epicardium layers do affect the photoacoustic signal received. The signal recorded is representative of the difference in optical and mechanical properties between the layers. Ablated and non-ablated tissue also present differences in spectra. The determined optical contrast could be used in the PA monitoring of RFA lesion to monitor the extension of the lesion to the edge of the myocardium-epicardium border avoiding complications related to over ablation.

  18. A first-in-man study to evaluate the safety, tolerability, and pharmacokinetics of pasireotide (SOM230, a multireceptor-targeted somatostatin analog, in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Golor G

    2012-04-01

    Full Text Available Georg Golor1, Ke Hu2, Matthieu Ruffin3, Alexandra Buchelt3, Emmanuel Bouillaud3, Yanfeng Wang2, Mario Maldonado31Parexel International GmbH, Berlin, Germany; 2Novartis Pharmaceuticals, East Hanover, NJ, USA; 3Novartis Pharma AG, Basel, SwitzerlandAbstract: Pasireotide (SOM230 is a multireceptor-targeted somatostatin analog with high binding affinity for four of the five somatostatin receptor subtypes (sst1,2,3 and sst5, and potential clinical activity in several neuroendocrine and oncologic conditions, including acromegaly, Cushing’s disease, and neuroendocrine tumors (NET. This manuscript reports the first-in-man dose-escalation study of pasireotide, evaluating its safety, tolerability, and pharmacokinetics (PK in healthy male volunteers. A single dose of pasireotide 1–1200 µg was administered subcutaneously in four to eight subjects per dose level, with two additional subjects per cohort administered placebo. PK and safety evaluations were carried out over 7 days post-dose. Growth hormone (GH suppression was evaluated using a GH-releasing hormone stimulation test on Day –1 and Day 1 at 3–5 hours post-injection. Seventy-two subjects completed the study. Pasireotide was well tolerated with no serious adverse events observed at any dose. Transient elevations in blood glucose levels were observed 2–6 hours after administration of pasireotide at doses between 200 µg and 1200 µg, but this resolved without intervention by 23 hours post-dosing. The maximum tolerable dose was not established within the tested range. Pasireotide demonstrated a favorable PK profile with fast absorption (tmax: 0.25–0.5 hours, low clearance (CL/F: 8–13 L/hour, long effective elimination half-life (mean t½,ß: 7–11 hours, and a proportional dose-exposure relationship. GH suppression of 79%–96% was observed at single pasireotide doses between 200 µg and 1200 µg. In conclusion, pasireotide demonstrated favorable safety, tolerability, and PK profiles

  19. Weight Cycling Increases T-Cell Accumulation in Adipose Tissue and Impairs Systemic Glucose Tolerance

    OpenAIRE

    Anderson, Emily K.; Gutierrez, Dario A.; Kennedy, Arion; Hasty, Alyssa H.

    2013-01-01

    Obesity is one of the leading causes of morbidity in the U.S. Accumulation of proinflammatory immune cells in adipose tissue (AT) contributes to the development of obesity-associated disorders. Weight loss is the ideal method to counteract the negative consequences of obesity; however, losses are rarely maintained, leading to bouts of weight cycling. Fluctuations in weight have been associated with worsened metabolic and cardiovascular outcomes; yet, the mechanisms explaining this potential c...

  20. Withdrawal periods and tissue tolerance after intramammary antibiotic treatment of dairy goats with clinical mastitis

    OpenAIRE

    J. Karzis; E.F. Donkin; I.M. Petzer

    2007-01-01

    The aim of this study was to determine withdrawal periods (WP) and tissue irritation after administration of three intramammary antibiotics [Curaclox LC (Norbrook (ARK AH)], Spectrazol Milking Cow (Schering-Plough AH) and Rilexine 200 LC [Logos Agvet (Virbac)] in goats with clinical mastitis.Withdrawal periods in goats with clinical mastitis treated with Curaclox LC, were not significantly different from those recommended for use in cows (72 h) with (67 h) or without (48 h) the 24 h man...

  1. Microarray Expression Profiles of 20.000 Genes across 23 Healthy Porcine Tissues

    DEFF Research Database (Denmark)

    Hornshøj, Henrik; Conley, Lene Nagstrup; Hedegaard, Jakob

    2007-01-01

    Gene expression microarrays have been intensively applied to screen for genes involved in specific biological processes of interest such as diseases or responses to environmental stimuli. For mammalian species, cataloging of the global gene expression profiles in large tissue collections under...

  2. Quantification of Tissue Inhibitor of Metalloproteinases 2 in Plasma from Healthy Donors and Cancer Patients

    DEFF Research Database (Denmark)

    Larsen, M B; Stephens, R W; Brünner, Nils

    2005-01-01

    Tissue inhibitor of metalloproteinases (TIMP)-2 is a highly conserved molecule, which binds both active and latent matrix metalloproteinase (MMP)-2. TIMP-2 is also involved in the activation of MMP-2 on the cell surface. A quantitative enzyme-linked immunosorbent assay (ELISA) was established...

  3. Diversity of Duodenal and Rectal Microbiota in Biopsy Tissues and Luminal Contents in Healthy Volunteers.

    Science.gov (United States)

    Li, Gangping; Yang, Min; Zhou, Kan; Zhang, Lei; Tian, Lugao; Lv, Shangze; Jin, Yu; Qian, Wei; Xiong, Hanhua; Lin, Rong; Fu, Yu; Hou, Xiaohua

    2015-07-01

    The diverse microbial communities that colonize distinct segments of the gastrointestinal tract are intimately related to aspects of physiology and the pathology of human health. However, most recent studies have focused on the rectal or fecal microbiota, and the microbial signature of the duodenum is poorly studied. In this study, we compared the microbiota in duodenal and rectal samples to illustrate the characteristic microbial signatures of the duodenum in healthy adults. Nine healthy volunteers donated biopsies and luminal contents from the duodenum and rectum. To determine the composition and diversity of the microbiota, 454- pyrosequencing of bacterial 16S rRNA was performed and multiple bioinformatics analyses were applied. The α-diversity and phylogenetic diversity of the microbiota in the duodenal samples were higher than those of the rectal samples. There was higher biodiversity among the microbiota isolated from rectal biopsies than feces. Proteobacteria were more highly represented in the duodenum than in the rectum, both in the biopsies and in the luminal contents from the healthy volunteers (38.7% versus 12.5%, 33.2% versus 5.0%, respectively). Acinetobacter and Prevotella were dominant in the duodenum, whereas Bacteroides and Prevotella were dominant in the rectum. Additionally, the percentage of OTUs shared in biopsy groups was far higher than in the luminal group (43.0% versus 26.8%) and a greater number of genera was shared among the biopsies than the luminal contents. Duodenal samples demonstrated greater biological diversity and possessed a unique microbial signature compared with the rectum. The mucosa-associated microbiota was more relatively conserved than luminal samples.

  4. Alterations in energy homeostasis to favour adipose tissue gain: A longitudinal study in healthy pregnant women.

    Science.gov (United States)

    Abeysekera, Minoli V; Morris, Jack A; Davis, Gregory K; O'Sullivan, Anthony J

    2016-02-01

    Pregnancy is associated with an increase in body fat; however, excessive gestational weight gain predisposes to significant maternal and neonatal morbidity and mortality. It remains unclear whether alterations in energy homeostasis have a major influence on fat storage. To evaluate longitudinal changes in body composition and energy metabolism in healthy pregnant women. Body composition, energy expenditure and energy intake were measured longitudinally in 26 women with singleton pregnancies at 12-14 weeks, 24-26 weeks and 34-36 weeks of gestation. Fat mass (FM) and lean body mass (LBM) were measured using bio-impedance analysis, total energy expenditure (TEE) using the Sensewear Armband and energy intake through a 3-day food recall diary. Throughout pregnancy, all women remained healthy. Body weight increased by 10.8 ± 3.9 kg, from 67.3 ± 14.1 kg to 78.1 ± 13.8 kg from the first to the third trimester (P Body fat percentage increased by 4.5 ± 4.2% (P change significantly throughout pregnancy. Healthy women increase FM during pregnancy despite slight increases in TEE and no change in energy intake. This suggests that energy storage efficiency improves during pregnancy, which may be related to alterations in gut microbiota and activation of anabolic pathways during pregnancy. Clarifying factors leading to this more efficient fat and energy storing state, and the role of the pregnancy-related changes in gut microbiota, may be important for managing gestational weight gain. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  5. Oxidative effects of extremely low frequency magnetic field and radio frequency radiation on testes tissues of diabetic and healthy rats.

    Science.gov (United States)

    Kuzay, D; Ozer, C; Sirav, B; Canseven, A G; Seyhan, N

    2017-01-01

    With the development of technology, people are increasingly under the exposure of electromagnetic fields. Individuals with chronic diseases such as diabetes are now long-term exposed to Radio Frequency-RF radiation and extremely low frequency (ELF) magnetic fields (MFs). The purpose of this present study is to investigate oxidative effects and antioxidant parameters of ELF MFs and RF radiation on testis tissue in diabetic and healthy rats. Wistar male rats were divided into 10 groups. Intraperitoneal single dose STZ (65 mg/kg) dissolved in citrate buffer (0.1M (pH 4.5)) was injected to diabetes groups. ELF MFs and RF radiation were used as an electromagnetic exposure for 20 min/day, 5 days/week for one month. Testis tissue oxidant malondialdehyde (MDA), and antioxidants glutathione (GSH), and total nitric oxide (NOx) levels were determined. The results of ANOVA and Mann-Whitney tests were compared; p radiation resulted in an increase in testicular tissue MDA and NOX levels (p radiation practices increased the oxidative stress in testis tissue while causing a decrease in antioxidant level which was more distinctive in diabetic rats (Tab. 1, Fig. 3, Ref. 30).

  6. Influence of enrofloxacin traces in drinking water to doxycycline tissue pharmacokinetics in healthy and infected by Mycoplasma gallisepticum broiler chickens.

    Science.gov (United States)

    Gbylik-Sikorska, Malgorzata; Posyniak, Andrzej; Sniegocki, Tomasz; Sell, Bartosz; Gajda, Anna; Sawicka, Anna; Olszewska-Tomczyk, Monika; Bladek, Tomasz; Tomczyk, Grzegorz; Zmudzki, Jan

    2016-04-01

    Most of antibiotics, administrated in the treatment of poultry diseases are dissolved in drinking water, and it can lead to water supply systems contamination, especially when the regular cleaning is not using. This situation can lead to unconscious administration of low doses of antibiotics to untreated animals. The aim of this study was to clarify the impact of the exposure of enrofloxacin traces (500 μg l(-1)) to doxycycline pharmacokinetics in healthy and experimentally Mycoplasma gallisepticum infected broiler chickens., Two experimental groups, received of enrofloxacin in water and all groups, received 20 mg kg(-1) bw of doxycycline. The compounds concentrations in muscles and livers were determined by LC-MS/MS. The maximum drug tissue concentration (Cmax) of doxycycline was highest in liver obtained from infected chickens which, received enrofloxacin traces (ENR + DC/MG). It was about 40% higher than in healthy chickens from group I which received only doxycycline. It was found that the concentration-time curve AUC(0-t) values in group ENR + DC/MG were almost 75% higher than in the group (DC) and 35% higher than in group (ENR + DC) which also received enrofloxacin traces. The constant exposure of broiler chickens on enrofloxacin traces as well as infection, may significantly influenced on doxycycline tissue pharmacokinetic profile.

  7. Intake of St John's wort improves the glucose tolerance in healthy subjects who ingest metformin compared with metformin alone

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Pedersen, Rasmus Steen; Damkier, Per

    2015-01-01

    AIMS: Our objective was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St John's wort and the antidiabetic drug metformin. METHODS: We performed an open cross-over study in 20 healthy male subjects, who received 1 g...

  8. Mechanisms for tolerance of very high tissue phosphorus concentrations in Ptilotus polystachyus.

    Science.gov (United States)

    Aziz, Tariq; Lambers, Hans; Nicol, Dion; Ryan, Megan H

    2015-04-01

    Study of plants with unusual phosphorus (P) physiology may assist development of more P-efficient crops. Ptilotus polystachyus grows well at high P supply, when shoot P concentrations ([P]) may exceed 40 mg P g(-1) dry matter (DM). We explored the P physiology of P. polystachyus seedlings grown in nutrient solution with 0-5 mM P. In addition, young leaves and roots of soil-grown plants were used for cryo-scanning electron microscopy and X-ray microanalysis. No P-toxicity symptoms were observed, even at 5 mM P in solution. Shoot DM was similar at 0.1 and 1.0 mM P in solution, but was ∼14% lower at 2 and 5 mM P. At 1 mM P, [P] was 36, 18, 14 and 11 mg P g(-1) DM in mature leaves, young leaves, stems and roots, respectively. Leaf potassium, calcium and magnesium concentrations increased with increasing P supply. Leaf epidermal and palisade mesophyll cells had similar [P]. The root epidermis and most cortical cells had senesced, even in young roots. We conclude that preferential accumulation of P in mature leaves, accumulation of balancing cations and uniform distribution of P across leaf cell types allow P. polystachyus to tolerate very high leaf [P].

  9. 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

    OBJECTIVE: We studied how an acute bout of exercise influences expression and concentration of adiponectin and regulators of adiponectin in adipose tissue and plasma. DESIGN AND METHODS: Eight overweight and eight lean males were examined by large-pore microdialysis in s.c. abdominal adipose tissue...... increased the SCAAT interstitial adiponectin concentration in both overweight and lean subjects and concentrations did not differ between groups. Plasma adiponectin did not increase during exercise and was similar in overweight and lean subjects. Adiponectin mRNA in SCAAT decreased during exercise...... and was similar in overweight and lean subjects. Surprisingly, the interstitial adiponectin concentration in SCAAT was only 20% of the plasma concentration. SCAAT interleukin-6 (IL-6) microdialyzate and plasma concentrations and SCAAT IL-6 mRNA increased during exercise in both groups. Tumor necrosis factor- (TNF...

  10. Quantification of differences in the effective atomic numbers of healthy and cancerous tissues: A discussion in the context of diagnostics and dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, M. L. [School of Applied Sciences and Health Innovation Research Institute, RMIT University, Melbourne 3000 (Australia); Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne 3001 (Australia) and Medical Physics, WBRC, Alfred Hospital, Melbourne 3000 (Australia)

    2012-09-15

    Purpose: There are a range of genetic and nongenetic factors influencing the elemental composition of different human tissues. The elemental composition of cancerous tissues frequently differs from healthy tissue of the same organ, particularly in high-Z trace element concentrations. For this reason, one could suggest that this may be exploited in diagnostics and perhaps even influence dosimetry. Methods: In this work, for the first time, effective atomic numbers are computed for common cancerous and healthy tissues using a robust, energy-dependent approach between 10 keV and 100 MeV. These are then quantitatively compared within the context of diagnostics and dosimetry. Results: Differences between effective atomic numbers of healthy and diseased tissues are found to be typically less than 10%. Fibrotic tissues and calcifications of the breast exhibit substantial (tens to hundreds of percent) differences to healthy tissue. Expectedly, differences are most pronounced in the photoelectric regime and consequently most relevant for kV imaging/therapy and radionuclides with prominent low-energy peaks. Cancerous tissue of the testes and stomach have lower effective atomic numbers than corresponding healthy tissues, while diseased tissues of the other organ sites typically have higher values. Conclusions: As dose calculation approaches improve in accuracy, there may be an argument for the explicit inclusion of pathologies. This is more the case for breast, penile, prostate, nasopharyngeal, and stomach cancer, less so for testicular and kidney cancer. The calculated data suggest dual-energy computed tomography could potentially improve lesion identification in the aforementioned organs (with the exception of testicular cancer), with most import in breast imaging. Ultimately, however, the differences are very small. It is likely that the assumption of a generic 'tissue ramp' in planning will be sufficient for the foreseeable future, and that the Z differences do

  11. [Repair of lower extremity soft tissue defect with free musculo-cutaneous flaps bridging with healthy contralateral posterior tibial vessel].

    Science.gov (United States)

    Chengde, Xia; Haiping, Di; Jidong, Xue; Yaohua, Zhao; Xiaoliang, Li; Qiang, Li; Xihua, Niu; Yonglin, Li; Hongkai, Lian

    2015-05-01

    To observe the clinical effects of free musculo-cutaneous flap bridging with contralateral posterior tibial vessel on repair of lower extremity soft tissue defect. From February 2006 to June 2013, 10 patients with soft tissue defect on lower shank and foot were included. The posterior tibial vessel on healthy lower extremity was chosen as recipient vessel and anastomosed with free latissimus dorsi musculo-cutaneous flap, or free latissimus dorsi musculo-cutaneous flap combined with thoracic-umbilical skin flap or anterolateral femoral musculo-cutaneous flap. The retrograde bridged flap was transposed to repair defect on contralateral lower shank and foot. The wound area ranged from 40 cm x 21 cm to 22 cm x 15 cm, with flap size from 48 cm x 26 cm to 25 cm x 18 cm. Meanwhile the defects on donor sites were covered with skin graft and both lower extremities were fixed with kirschner wires at middle tibia and calcaneus. The kirschner wires were removed at 4 weeks and pedicles were cut off 5-8 weeks postoperatively. Six patients received posterior tibial vessel reanastomosis at the same time of pedicle cutting. All the 10 flaps survived and 3 patients received thinning of flaps due to excessive thickness. During the follow-up period of 3 months to 2 years follow up, the ambulatory function of injured legs recovered gradually with satisfactory appearance. The reanastomosed posterior tibial vessel on the healthy side was recovered. Appropriate bridged musculo-cutaneous flaps is suitable for extensive soft tissue defect of lower shank and foot. It is a safe and effective method for limb salvage.

  12. Renal tolerance to nonhomogenous irradiation: Comparison of observed effects to predictions of normal tissue complication probability from different biophysical models

    Energy Technology Data Exchange (ETDEWEB)

    Flentje, M.; Hensley, F.; Gademann, G.; Wannenmacher, M. (Univ. of Heidelberg (Germany)); Menke, M. (German Cancer Research Center, Heidelberg (Germany))

    1993-09-01

    A patient series was analyzed retrospectively as an example of whole organ kidney irradiation with an inhomogenous dose distribution to test the validity of biophysical models predicting normal tissue tolerance to radiotherapy. From 1969 to 1984, 142 patients with seminoma were irradiated to the paraaortic region using predominantly rotational techniques which led to variable but partly substantial exposure of the kidneys. Median follow up was 8.2 (2.1-21) years and actuarial 10-year survival (Kaplan-Meier estimate) 82.8%. For all patients 3-dimensional dose distributions were reconstructed and normal tissue complication probabilities for the kidneys were generated from the individual dose volume histograms. To this respect different published biophysical algorithms were introduced in a 3-dimensional-treatment planning system. In seven patients clinically manifest renal impairment was observed (interval 10-84 months). An excellent agreement between predicted and observed effects was seen for two volume-oriented models, whereas complications were overestimated by an algorithm based on critical element assumptions. Should these observations be confirmed and extended to different types of organs corresponding algorithms could easily be integrated into 3-dimensional-treatment planning programs and be used for comparing and judging different plans on a more biologically oriented basis.

  13. Withdrawal periods and tissue tolerance after intramammary antibiotic treatment of dairy goats with clinical mastitis

    Directory of Open Access Journals (Sweden)

    J. Karzis

    2007-09-01

    Full Text Available The aim of this study was to determine withdrawal periods (WP and tissue irritation after administration of three intramammary antibiotics [Curaclox LC (Norbrook (ARK AH], Spectrazol Milking Cow (Schering-Plough AH and Rilexine 200 LC [Logos Agvet (Virbac] in goats with clinical mastitis.Withdrawal periods in goats with clinical mastitis treated with Curaclox LC, were not significantly different from those recommended for use in cows (72 h with (67 h or without (48 h the 24 h mandatory safety margin while Spectrazol caused a significantly longer withdrawal period (122 h than that recommended for use in cattle with (60 h and without (36 h the 24h safety margin. The withdrawal period of clinical mastitis cases treated with Rilexine 200 LC was 48 h compared to the 96 h recommended for use in cows.A linear model of regression with factors influencing the WP in goats with clinical mastitis was as follows : WP = 30.21 + 4.692 (sampling time + 22.11 (udder pathology - 13.6 (floccules - 0.00649 (milk yield.Somatic Cell Counts (SCC of milk from udder halves with clinical mastitis ranged from 7 053 x 103 to 7 948 x 103 cells per mℓ without isolations of bacteria and between 6 476 x 103 and 8 479 x 103 cells per mℓ with isolations of bacteria. Most of the variation in SCC could not be explained and the California Milk Cell Test (CMCT and SCC on their own were not reliable methods for mastitis diagnosis. However, CMCT and SCC were indicators of udder irritation. In goats without clinical mastitis, Spectrazol Milking Cow caused the least tissue irritation followed by Rilexine 200 LC and Curaclox LC. For goats with clinical mastitis, Rilexine 200 LC caused the least irritation, followed by Curaclox LC while Spectrazol Milking Cow caused the most irritation.

  14. Withdrawal periods and tissue tolerance after intramammary antibiotic treatment of dairy goats with clinical mastitis.

    Science.gov (United States)

    Karzis, J; Donkin, E F; Petzer, I M

    2007-12-01

    The aim of this study was to determine withdrawal periods (WP) and tissue irritation after administration of three intramammary antibiotics [Curaclox LC (Norbrook (ARK AH)], Spectrazol Milking Cow (Schering-Plough AH) and Rilexine 200 LC [Logos Agvet (Virbac)] in goats with clinical mastitis. Withdrawal periods in goats with clinical mastitis treated with Curaclox LC, were not significantly different from those recommended for use in cows (72 h) with (67 h) or without (48 h) the 24 h mandatory safety margin while Spectrazol caused a significantly longer withdrawal period (122 h) than that recommended for use in cattle with (60 h) and without (36 h) the 24h safety margin. The withdrawal period of clinical mastitis cases treated with Rilexine 200 LC was 48 h compared to the 96 h recommended for use in cows. A linear model of regression with factors influencing the WP in goats with clinical mastitis was as follows: WP = 30.21 + 4.692 (sampling time) + 22.11 (udder pathology) - 13.6 (floccules) - 0.00649 (milk yield). Somatic Cell Counts (SCC) of milk from udder halves with clinical mastitis ranged from 7,053 x 10(3) to 7,948 x 10(3) cells per ml without isolations of bacteria and between 6,476 x 10(3) and 8,479 x 10(3) cells per ml with isolations of bacteria. Most of the variation in SCC could not be explained and the California Milk Cell Test (CMCT) and SCC on their own were not reliable methods for mastitis diagnosis. However, CMCT and SCC were indicators of udder irritation. In goats without clinical mastitis, Spectrazol Milking Cow caused the least tissue irritation followed by Rilexine 200 LC and Curaclox LC. For goats with clinical mastitis, Rilexine 200 LC caused the least irritation, followed by Curaclox LC while Spectrazol Milking Cow caused the most irritation.

  15. Study on trace elements behaviour in cancerous and healthy tissues of colon, breast and stomach: Total reflection X-ray fluorescence applications

    Science.gov (United States)

    Magalhães, T.; Carvalho, M. L.; Von Bohlen, A.; Becker, M.

    2010-06-01

    In this work Total-reflection X-ray fluorescence (TXRF) was used to analyse healthy and cancerous tissues of the same individual along several contiguous thin sections of each tissue. Thirty two samples (16 pairs) of breast tissue, 30 samples (15 pairs) of intestine tissue and 10 samples (5 pairs) of stomach tissue were analysed. The samples were obtained in Civil Hospitals of Germany (Dortmund) and Portugal (Lisbon). The elemental distribution of P, S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br, Rb, Sr and Pb in these samples was studied. Descriptive statistics based on bar graphics and hypotheses tests and also an automatic classification based on hierarchical grouping analysis was used for the several analysed tissues. It was shown that the behaviour of the elements is tissue dependent. Some elements, like P and K exhibit the same behaviour in all the analysed tissue types. They have increased concentrations in all cancerous tissues. Unlike, other elements like Br show completely different behaviour depending on the tissue: similar concentration in healthy and cancerous stomach, decreased levels in colon cancerous tissues and enhanced concentrations in breast was observed. Moreover cancer tissues present decreased Se concentrations on colon and increased on breast.

  16. Alveolar gas exchange and tissue deoxygenation during exercise in type 1 diabetes patients and healthy controls.

    Science.gov (United States)

    Peltonen, Juha E; Koponen, Anne S; Pullinen, Katri; Hägglund, Harriet; Aho, Jyrki M; Kyröläinen, Heikki; Tikkanen, Heikki O

    2012-05-31

    We used near-infrared spectroscopy to investigate whether leg and arm skeletal muscle and cerebral deoxygenation differ during incremental cycling exercise in men with type 1 diabetes (T1D, n=10, mean±SD age 33±7 years) and healthy control men (matched by age, anthrometry, and self-reported physical activity, CON, n=10, 32±7 years) to seek an explanation for lower aerobic capacity (˙VO2peak) often reported in T1D. T1D had lower ˙VO2peak (35±4mlkg(-1)min(-1) vs. 43±8mlkg(-1)min(-1), Prate (219±33W vs. 290±44W, Prate, but not at peak exercise, while arm muscle and cerebral deoxygenation were similar. Thus, in T1D compared with CON, faster leg muscle deoxygenation suggests limited circulatory ability to increase O(2) delivery as a plausible explanation for lower ˙VO2peak and earlier fatigue in T1D.

  17. Characterization of immune cell populations in oral mucosal tissue of healthy adult cats.

    Science.gov (United States)

    Harley, R; Gruffydd-Jones, T J; Day, M J

    2003-01-01

    The aim of this study was to characterize the leucocyte subsets present in the oral mucosa of healthy cats. Immunohistochemical labelling and computer-assisted morphometric analysis was used to identify expression of MHC class II, CD3, CD79a, IgG, IgM, IgA, and leucocyte antigen L1 (L1) by cells in sections from 19 cats, and expression of CD4 and CD8 by cells in sections from 17 cats. Mast cells were detected by toluidine blue staining. In the epithelial compartment, CD3(+) intraepithelial lymphocytes were detected, and CD8(+) cells were more common than CD4(+) cells. MHC class II labelling revealed intraepithelial and subepithelial cells with a characteristic dendritic morphology. In some sections these dendritic cells were closely associated with subepithelial clusters of CD3(+) T cells containing both CD4(+) and CD8(+) cells. In the lamina propria and submucosal compartments, the cells most commonly identified were mast cells. CD3(+) T-lymphocytes were also observed, and CD4(+) and CD8(+) cells were detected in similar numbers. L1(+) and CD79(+) cells were detected least frequently. The few plasma cells present were generally found to be either IgG(+) or IgA(+). Within the stroma surrounding the salivary glands, CD79a(+) and IgA(+) cells predominated. Slight epithelial labelling for L1 was seen in some sections. The normal feline oral mucosa clearly contains a range of immune cell populations.

  18. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast

    DEFF Research Database (Denmark)

    Nilsson, Anne C; Ostman, Elin M; Holst, Jens Juul

    2008-01-01

    Low-glycemic index (GI) foods and foods rich in whole grain are associated with reduced risk of type 2 diabetes and cardiovascular disease. We studied the effect of cereal-based bread evening meals (50 g available starch), varying in GI and content of indigestible carbohydrates, on glucose...... tolerance and related variables after a subsequent standardized breakfast in healthy subjects (n = 15). At breakfast, blood was sampled for 3 h for analysis of blood glucose, serum insulin, serum FFA, serum triacylglycerides, plasma glucagon, plasma gastric-inhibitory peptide, plasma glucagon-like peptide-1...... (GLP-1), serum interleukin (IL)-6, serum IL-8, and plasma adiponectin. Satiety was subjectively rated after breakfast and the gastric emptying rate (GER) was determined using paracetamol as a marker. Breath hydrogen was measured as an indicator of colonic fermentation. Evening meals with barley kernel...

  19. Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

    Directory of Open Access Journals (Sweden)

    Meng Wang

    2015-09-01

    Full Text Available L-3-n-butylphthalide (L-NBP is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40, or multiple doses of 160 mg twice daily for 7 days (n=12. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE, death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

  20. Safety, Tolerability, and Pharmacokinetics of Therapeutic and Supratherapeutic Doses of Tramadol Hydrochloride in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Multiple-Ascending-Dose Study.

    Science.gov (United States)

    DeLemos, Byron; Richards, Henry M; Vandenbossche, Joris; Ariyawansa, Jay; Natarajan, Jaya; Alexander, Binu; Ramakrishna, Tage; Murtaugh, Thomas; Stahlberg, Hans-Jürgen

    2017-09-07

    This randomized, double-blind, parallel-group multiple-ascending-dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91.7%) completed the study. The AUCtau,ss of tramadol increased approximately 2.2- and 3.6-fold for the (+) enantiomer and 2.0- and 3.5-fold for the (-) enantiomer with increasing dose from 200 to 400  and 600 mg/day, whereas the Cmax,ss increased 2.1- and 3.3-fold for the (+) enantiomer and 2.0- and 3.2-fold for the (-) enantiomer. Overall, 21 participants (87.5%) participants reported ≥1 treatment-emergent adverse event; most frequent were nausea (17 of 24, 70.8%) and vomiting (7 of 24, 29.2%). Vomiting (affected participants and events) increased with increasing dose from 200 to 600 mg/day but was mild (5 of 24) or moderate (2 of 24) in severity. All tested dosage regimens of tramadol showed acceptable safety and tolerability profile for further investigation in a thorough QT/QTc study. © 2017, The American College of Clinical Pharmacology.

  1. Early postprandial low-grade inflammation after high-fat meal in healthy rats: possible involvement of visceral adipose tissue.

    Science.gov (United States)

    Magné, Joëlle; Mariotti, François; Fischer, Romy; Mathé, Véronique; Tomé, Daniel; Huneau, Jean François

    2010-06-01

    In the postprandial period, low-grade inflammation may contribute to vascular endothelial dysfunction, a hallmark of atherogenesis. Little is known about the involvement of the adipose tissue in the initiation of the postprandial inflammatory response such as obtained after a high-saturated fat meal (HFM). In the present study, we first studied the time course of appearance of systemic inflammation after a HFM in healthy rats, and then we investigated whether a HFM activates the inflammatory signaling in the visceral adipose tissue, with a focus on the key component, nuclear factor-kappaB (NF-kappaB). Two hours after the HFM, plasma IL-6 and PAI-1, but not plasma C-reactive protein and soluble intracellular adhesion molecule-1, showed a marked, transient increase. These changes were specific to the postprandial state as not observed after a control water load. Neutrophils count and activation markers CD11B and CD62L, assessed by flow cytometry, also rose significantly 2 h after the HFM, while remaining steady after the control. At the same time, the HFM decreased significantly B-cell count and expression of the activation marker CD62L. Interestingly, at the same early time after the HFM, in the visceral adipose tissue, there was a 2.2-fold increase in the activation of NF-kappaB (p65) in nuclear extract and an increase in IL-6 mRNA. As far as we know, this is the first study evidencing an acute, postprandial activation of inflammation in visceral adipose tissue. This early activation of NF-kappaB pathway after a HFM may play a triggering role in the initiation of the complex postprandial proatherogenic phenotype. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  2. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Deman, Pierre [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Vautrin, Mathias [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); DOSIsoft, Cachan (France); Edouard, Magali [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Stupar, Vasile [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Bobyk, Laure; Farion, Regine [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Elleaume, Helene [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Remy, Chantal; Barbier, Emmanuel L. [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Esteve, Francois [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Adam, Jean-Francois, E-mail: adam@esrf.fr [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France)

    2012-03-15

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  3. ROC analysis of subcutaneous adipose tissue topography (SAT-Top) in female coronary heart disease patients and healthy controls.

    Science.gov (United States)

    Wallner, Sandra Johanna; Horejsi, Renate; Zweiker, Robert; Watzinger, Norbert; Möller, Reinhard; Schnedl, Wolfgang Johann; Schauenstein, Konrad; Tafeit, Erwin

    2008-06-01

    The aim of this study was to investigate whether subcutaneous adipose tissue topography (SAT-Top) is different in female CHD patients (n=26) and healthy controls (n=36) matched to age, body size, weight, and BMI. The thicknesses of SAT layers were measured by LIPOMETER at 15 specified body sites. To calculate the power of the different body sites to discriminate between CHD women and healthy controls, receiver operating characteristic (ROC) curve analysis was performed. For each parameter, sensitivity and specificity were calculated at different cutoff points. CHD women showed a significant decrease to 78.36% (p=0.012) at body site 11-front thigh, 73.10% (p=0.012) at 12-lateral thigh, 72.20% (p=0.009) at 13-rear thigh, 66.43% (pSAT thickness at each measured body site is able to discriminate between the two subject groups. The good discrimination results obtained for the present dataset are encouraging enough to recommend applying LIPOMETER SAT-Top measurements in further studies to investigate individual risks for CHD.

  4. Increased WD-repeat containing protein 1 in interstitial fluid from ovarian carcinomas shown by comparative proteomic analysis of malignant and healthy gynecological tissue.

    Science.gov (United States)

    Haslene-Hox, Hanne; Oveland, Eystein; Woie, Kathrine; Salvesen, Helga B; Wiig, Helge; Tenstad, Olav

    2013-11-01

    We aimed to identify differentially expressed proteins in interstitial fluid from ovarian cancer employing multiple fractioning and high resolution mass spectrometry-based proteomic analysis, and asked whether specific proteins that may serve as biomarker candidates or therapeutic targets could be identified. High throughput proteomics was conducted on immunodepleted and fractioned interstitial fluid from pooled samples of ovarian carcinomas, using endometrial carcinomas and healthy ovarian tissue as controls. Differential analysis revealed the up-regulation of extracellular proteasomes in tumor interstitial fluid compared to the healthy control. Moreover, a number of differentially expressed proteins in interstitial fluid from ovarian carcinomas compared with control tissues were identified. Detection of proteasome 20S related proteins in TIF compared to IF from healthy tissue indicates that the 20S proteasome can have a role in the tumor microenvironment. Six selected proteins, CEACAM5, FREM2, MUC5AC, TFF3, PYCARD and WDR1, were independently validated in individual tumor lysates from ovarian carcinomas by multiple reaction monitoring initiated detection and sequence analysis, Western blot and/or selected reaction monitoring. Quantification of specific proteins revealed substantial heterogeneity between individual samples. Nevertheless, WD repeat-containing protein 1 was confirmed as being significantly overexpressed in interstitial fluid from ovarian carcinomas compared to healthy ovarian tissue by Orbitrap analysis of individual native interstitial fluid from ovarian and endometrial carcinomas and healthy ovarian tissue. We suggest that this protein should be explored as a therapeutic target in ovarian carcinomas. This article is part of a Special Issue entitled: An Updated Secretome.

  5. Six different fat tolerance tests in young, healthy subjects –gender dependent postprandial lipemia and glucose

    DEFF Research Database (Denmark)

    Rasmussen, Ole Winther; Lauszus, Finn Friis

    2016-01-01

    tolerenctes (OFTT) with varying amoun of saturated fat. Methods: With six different types of fatin random order to tomatoes we measured postprandial lipemia, lipoprotein, glucose and insulin increments for eight hours in 14 young lean healthy students, seven of each gender. The area under the curve (AUC......) was dtermined for the postprandial values. Results: The meals with six types of butters had similar postprandial response even if the saturated fat content varied with 50%.Gender significantly affected the TG responses, as time to pesk was 90 minutes in women and 180 min in men. Postprandial AUC was higherwith...... responses and postprandial lipemia was gender-specific. Replacement of saturated fat by mono- or polyunsaturated fat did not alter postprandial lipemia during single OFTT...

  6. Lack of association between overload and peri-implant tissue loss in healthy conditions.

    Science.gov (United States)

    Afrashtehfar, Kelvin I; Afrashtehfar, Cyrus Dm

    2016-09-01

    Data sourcesPubMed, Ovid, EMBASE and LILACS were searched up to December 2011. In addition, the reference lists of the selected review papers were further hand searched. Language was limited to studies published only in English.Study selectionHuman and animal randomised clinical trials (RCT), systematic reviews of RCTs, non-randomised trials, case series that reported on the clinical, radiographic, and/or histological outcomes of dental/oral implants exposed to excessive load were considered eligible for inclusion.Data extraction and synthesisIdentified studies were evaluated by one non-blinded reviewer according to the selection criteria. When doubt arose co-authors assisted until consensus was reached. The data extracted from the clinical studies included study design, patients/implants/prostheses/loading time/follow-up time, type of intervention/methods, outcome, and, specific to animal studies, the animal model, intention to overload (ie yes or no), load mode, type of loading (ie dynamic or static), and microbial control if any. The heterogeneity among studies did not allow data to be combined.ResultsThe search strategy in addition to hand searching retrieved 726 potentially eligible studies after de-duplication. After screening the 41 full-text relevant studies and applying the selection criteria assessment, only three non-randomised split-mouth animal studies and one systematic review of animal experimental data were considered for inclusion. The non-randomised studies could not reveal any relationship between increased leverage on dental implants and marginal loss. The systematic review suggested that supra-occlusal contacts on uninflamed peri-implant bone tissue did not cause catabolism, whereas supra-occlusal contacts combined with inflammation significantly increased the plaque-induced catabolism.ConclusionsThe effect of implant overload on bone/implant loss in clinically well-integrated implants is poorly reported and provides little unbiased evidence to

  7. Impact of dosing regimen of custirsen, an antisense oligonucleotide, on safety, tolerability and cardiac repolarization in healthy subjects.

    Science.gov (United States)

    Rabinovich-Guilatt, Laura; Elgart, Anna; Erisson, Lavi; Willsie, Sandra K; Tessler, Shoshi; Barnett-Griness, Ofra; Pande, Amitkumar; Spiegelstein, Ofer

    2015-09-01

    Custirsen (OGX-011/TV-1011), a second-generation antisense oligonucleotide (ASO) that reduces clusterin production, is under investigation with chemotherapy in patients with solid tumours. Custirsen is associated with constitutional symptoms (CS) that may interfere with clinical pharmacology investigations, such as QT interval studies. Experience with other ASOs suggests NSAID premedication may ameliorate CS, but we observed suboptimal outcomes in healthy subjects given custirsen and NSAIDs. We sought to establish a custirsen regimen for future clinical pharmacology studies in healthy subjects. Subjects received custirsen (640 mg intravenously over 120 min) with dexamethasone premedication or increasing doses (320, 480, 640 mg over 6 days) of custirsen with dexamethasone premedication, then one full custirsen dose without premedication on day 8. Incidence/severity of adverse events (AEs) and extensive electrocardiogram readings were evaluated. Pharmacokinetic parameters were estimated. AEs included CS, elevated transaminases and prolonged activated partial thromboplastin time (aPTT) that were predominantly grade 1/2. Administration of increasing custirsen doses and dexamethasone premedication reduced the incidence of CS associated with full dose custirsen. Transaminase elevation showed a dose-dependent effect (0% at days 2, 4, 27% at day 6) with the highest custirsen doses. Increasing doses of custirsen may have mitigated the severity but not incidence of aPTT prolongation. Neither regimen was associated with cardiac repolarization changes in QT values or concentration-effect analyses. The custirsen pharmacokinetic profile was consistent with previous experience. Escalation of custirsen dose combined with dexamethasone premedication reduced CS associated with full dose custirsen and should be considered in future clinical pharmacology studies of custirsen. © 2015 The British Pharmacological Society.

  8. A novel magnetic stimulator increases experimental pain tolerance in healthy volunteers - a double-blind sham-controlled crossover study.

    Directory of Open Access Journals (Sweden)

    Rudie Kortekaas

    Full Text Available UNLABELLED: The 'complex neural pulse'(TM (CNP is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF. A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. TRIAL REGISTRATION: Dutch Cochrane Centre NTR1093.

  9. Effects of hydrochlorothiazide on the pharmacokinetics, pharmacodynamics, and tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants.

    Science.gov (United States)

    Devineni, Damayanthi; Vaccaro, Nicole; Polidori, David; Rusch, Sarah; Wajs, Ewa

    2014-05-01

    Many patients with type 2 diabetes mellitus (T2DM) also have hypertension, which is commonly treated with thiazide diuretics, including hydrochlorothiazide (HCTZ). Canagliflozin, a sodium glucose cotransporter 2 inhibitor developed for the treatment of T2DM, lowers plasma glucose by inhibiting renal glucose reabsorption, thereby increasing urinary glucose excretion and mild osmotic diuresis. Because patients with T2DM are likely to receive concurrent canagliflozin and HCTZ, potential interactions were evaluated. This study evaluated the effects of HCTZ on the pharmacokinetic and pharmacodynamic properties and tolerability of canagliflozin in healthy participants. This Phase I, single-center, open-label, fixed-sequence, 2-period study was conducted in healthy participants. During period 1, participants received canagliflozin 300 mg once daily for 7 days, followed by a 14-day washout period. During period 2, participants received HCTZ 25 mg once daily for 28 days, followed by canagliflozin 300 mg + HCTZ 25 mg once daily for 7 days. Blood samples were taken before and several times after administration on day 7 of period 1 and on days 28 and 35 of period 2 for canagliflozin and HCTZ pharmacokinetic analyses using LC-MS/MS. Blood and urine samples were collected for up to 24 hours after canagliflozin administration on day 1 of period 1 and day 35 of period 2 for pharmacodynamic glucose assessment. Tolerability was also evaluated. Thirty participants were enrolled (16 men, 14 women; all white; mean age, 43.7 years). Canagliflozin AUC during a dosing interval (T) at steady state (AUCτ,ss) and Cmax at steady state (Cmax,ss) were increased when canagliflozin was coadministered with HCTZ, with geometric mean ratios (90% CI) of 1.12 (1.08-1.17) and 1.15 (1.06-1.25), respectively. AUCτ,ss and Cmax,ss for HCTZ were similar with and without canagliflozin coadministration. The 24-hour mean renal threshold for glucose and mean plasma glucose were comparable for canagliflozin

  10. Reproducibility, interchangeability of measures, time to measure stabilization, and reference values of two tissue oximeters in healthy volunteers

    Science.gov (United States)

    Cournoyer, Alexis; Denault, André; Cossette, Sylvie; Fortier, Annik; Daoust, Raoul; Iseppon, Massimiliano; Chauny, Jean-Marc; Notebaert, Eric

    2016-09-01

    This study aimed to compare two tissue oximeters, the INVOS 5100c and the Equanox 7600, in terms of their reproducibility and the interchangeability of their measures. In a randomized order, three measurements were taken at six different sites on both sides of the body in 53 healthy volunteers. Intraclass correlation coefficients (ICC) and within-subject standard deviation (Sw) were calculated for each device. The ICCs were compared using Fisher r-to-z transformation and the Sw were compared using paired-sample t-tests. We found no difference between the reproducibility of the INVOS {ICC=0.92 [95% confidence interval (CI) 0.90 to 0.93]} and Equanox [ICC=0.90 (95% CI 0.88 to 0.93)] in terms of ICCs (p=0.06). However, the Equanox [Sw=1.96 (95% CI 1.91 to 2.02)] showed a better Sw than the INVOS [Sw=2.11 (95% CI 2.05 to 2.17)] (p=0.019). Also, when compared directly to stable condition, the readings produced by the two oximeters varied considerably [ICC 0.43 (95% CI 0.36 to 0.49)]. When taken individually, both tissue oximeters displayed good reproducibility, the Equanox being slightly better than the INVOS in terms of absolute reproducibility. However, when compared, the oximeters showed poor interdevices agreement. Reference values were also described.

  11. Pharmacokinetics, Safety, and Tolerability of Amygdalin and Paeoniflorin After Single and Multiple Intravenous Infusions of Huoxue-Tongluo Lyophilized Powder for Injection in Healthy Chinese Volunteers.

    Science.gov (United States)

    Li, Xiaobing; Shi, Fuguo; Zhang, Run; Sun, Chenglong; Gong, Chuting; Jian, Lingyan; Ding, Li

    2016-02-01

    Huoxue-Tongluo lyophilized powder for injection (HTLPI), a traditional Chinese medicine preparation, is a compound of Persicae semen and Paeoniae Radix Rubra that is used mainly for treating blood-stasis obstruction syndrome in the acute stage of cerebral ischemic stroke. Amygdalin (AD) and paeoniflorin (PF) are 2 typical bioactive components in HTLPI and were selected as indicators for this pharmacokinetic study of HTLPI. The objective of this study was to investigate the safety profile, tolerability, and pharmacokinetic properties of AD and PF after single and multiple intravenous infusions of HTLPI in healthy Chinese volunteers. Twenty-one healthy Chinese subjects were recruited for this open-label, single ascending-dose (3, 6, and 9 g) and multiple-dose (6 g, once daily) study. Safety profile was assessed by adverse events and physical examination throughout the study. Serial plasma and urine samples were analyzed by HPLC-MS/MS. Pharmacokinetic parameters of AD and PF were calculated using noncompartmental analysis. In the single-dose phase of the study, the mean maximum plasma concentration and the mean area under the plasma concentration-time curve of AD and PF increased proportionally with each dose escalation. In the multiple-dose phase, the steady state was achieved by day 4 after multiple-dose administration of 6 g HTLPI. Mean pharmacokinetic parameters achieved on day 1 were similar to those on day 7. No significant accumulation was observed after repeat doses of 6 g HTLPI. Approximately 79.6% of the administered AD and 48.4% of the administered PF were excreted unchanged in urine within 24 hours. No serious adverse events were observed during the entire study. The pharmacokinetic properties of AD and PF were linear after a single intravenous infusion of HTLPI in the dose range of 3-9 g. No systemic accumulation was observed with repeat doses of HTLPI. Sex had no significant effect on the pharmacokinetic properties of AD and PF. Intravenous infusion of

  12. Safety, tolerability, pharmacokinetics, and effects on human experimental pain of the selective ionotropic glutamate receptor 5 (iGluR5) antagonist LY545694 in healthy volunteers.

    Science.gov (United States)

    Petersen, Karin L; Iyengar, Smriti; Chappell, Amy S; Lobo, Evelyn D; Reda, Haatem; Prucka, William R; Verfaille, Steven J

    2014-05-01

    The objective of this study was to establish in healthy volunteers the maximally tolerated multiple dose (MTMD) of the ionotropic glutamate receptor 5 antagonist LY545694 (part A), and to investigate whether that dose had analgesic or antihyperalgesic effects in the brief thermal stimulation (BTS) pain model (Part B). Part A was a double-blind, placebo-controlled study in 3 groups of 10 healthy men. To simulate an extended-release formulation, study drug was administered orally over 6hours (12 equally divided aliquots at 30-minute intervals). Part B was a double-blind, placebo-controlled, double-dummy, 3-way crossover study in 27 healthy men. At each of the 3 study periods, subjects received either LY545694 (MTMD; as determined during part A) as a simulated, twice daily extended-release formulation for 4 doses over 3days, gabapentin (600mg 8hours apart; 6 doses over 3days; positive control), or matching placebo. The BTS model was induced twice with a 1-hour interval on each of the 2 study days, before drug administration and at the time of expected peak analgesia of LY545694. Plasma exposure for LY545694 was approximately linear over the 25- to 75-mg dose range. The MTMD of LY545694 was 25mg twice daily. Areas of secondary hyperalgesia were significantly smaller after administration of LY545694 and gabapentin compared with placebo (Ppainfulness of skin heating during BTS model induction. The most common treatment-emergent adverse event was dizziness. The results of this study suggest that LY545694 should be explored further as a potential treatment for chronic pain involving neuronal sensitization.

  13. N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats

    Directory of Open Access Journals (Sweden)

    Karolline S. da Silva

    2017-09-01

    Full Text Available Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin in healthy rats, associated or not with N-acetylcysteine (NAC treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization.Methods: Male Wistar rats were intraperitoneally injected with control (C or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML and pyrraline (PYR were determined by LC/mass spectrometry (LC-MS/MS and ELISA.Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups.Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE

  14. Comparative study of equine mesenchymal stem cells from healthy and injured synovial tissues: an in vitro assessment.

    Science.gov (United States)

    Fülber, Joice; Maria, Durvanei A; da Silva, Luis Cláudio Lopes Correia; Massoco, Cristina O; Agreste, Fernanda; Baccarin, Raquel Y Arantes

    2016-03-05

    Bone marrow and adipose tissues are known sources of mesenchymal stem cells (MSCs) in horses; however, synovial tissues might be a promising alternative. The aim of this study was to evaluate phenotypic characteristics and differentiation potential of equine MSCs from synovial fluid (SF) and synovial membrane (SM) of healthy joints (SF-H and SM-H), joints with osteoarthritis (SF-OA and SM-OA) and joints with osteochondritis dissecans (SF-OCD and SM-OCD) to determine the most suitable synovial source for an allogeneic therapy cell bank. Expression of the markers CD90, CD105, CD44, and CD34 in SF-H, SM-H, SF-OA, SM-OA, SF-OCD and SM-OCD was verified by flow cytometry, and expression of cytokeratin, vimentin, PGP 9.5, PCNA, lysozyme, nanog, and Oct4 was verified by immunocytochemistry. MSCs were cultured and evaluated for their chondrogenic, osteogenic and adipogenic differentiation potential. Final quantification of extracellular matrix and mineralized matrix was determined using AxioVision software. A tumorigenicity test was conducted in Balb-C(nu/nu) mice to verify the safety of the MSCs from these sources. Cultured cells from SF and SM exhibited fibroblastoid morphology and the ability to adhere to plastic. The time elapsed between primary culture and the third passage was approximately 73 days for SF-H, 89 days for SF-OCD, 60 days for SF-OA, 68 days for SM-H, 57 days for SM-OCD and 54 days for SM-OA. The doubling time for SF-OCD was higher than that for other cells at the first passage (P < 0.05). MSCs from synovial tissues showed positive expression of the markers CD90, CD44, lysozyme, PGP 9.5, PCNA and vimentin and were able to differentiate into chondrogenic (21 days) and osteogenic (21 days) lineages, and, although poorly, into adipogenic lineages (14 days). The areas staining positive for extracellular matrix in the SF-H and SM-H groups were larger than those in the SF-OA and SM-OA groups (P < 0.05). The positive mineralized matrix area in the SF-H group was

  15. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast.

    Science.gov (United States)

    Nilsson, Anne C; Ostman, Elin M; Holst, Jens J; Björck, Inger M E

    2008-04-01

    Low-glycemic index (GI) foods and foods rich in whole grain are associated with reduced risk of type 2 diabetes and cardiovascular disease. We studied the effect of cereal-based bread evening meals (50 g available starch), varying in GI and content of indigestible carbohydrates, on glucose tolerance and related variables after a subsequent standardized breakfast in healthy subjects (n = 15). At breakfast, blood was sampled for 3 h for analysis of blood glucose, serum insulin, serum FFA, serum triacylglycerides, plasma glucagon, plasma gastric-inhibitory peptide, plasma glucagon-like peptide-1 (GLP-1), serum interleukin (IL)-6, serum IL-8, and plasma adiponectin. Satiety was subjectively rated after breakfast and the gastric emptying rate (GER) was determined using paracetamol as a marker. Breath hydrogen was measured as an indicator of colonic fermentation. Evening meals with barley kernel based bread (ordinary, high-amylose- or beta-glucan-rich genotypes) or an evening meal with white wheat flour bread (WWB) enriched with a mixture of barley fiber and resistant starch improved glucose tolerance at the subsequent breakfast compared with unsupplemented WWB (P < 0.05). At breakfast, the glucose response was inversely correlated with colonic fermentation (r = -0.25; P < 0.05) and GLP-1 (r = -0.26; P < 0.05) and positively correlated with FFA (r = 0.37; P < 0.001). IL-6 was lower (P < 0.01) and adiponectin was higher (P < 0.05) at breakfast following an evening meal with barley-kernel bread compared with WWB. Breath hydrogen correlated positively with satiety (r = 0.27; P < 0.01) and inversely with GER (r = -0.23; P < 0.05). In conclusion, the composition of indigestible carbohydrates of the evening meal may affect glycemic excursions and related metabolic risk variables at breakfast through a mechanism involving colonic fermentation. The results provide evidence for a link between gut microbial metabolism and key factors associated with insulin resistance.

  16. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses.

    Directory of Open Access Journals (Sweden)

    Patricia L Hibberd

    Full Text Available BACKGROUND: Although Lactobacillus rhamnosus GG ATCC 53103 (LGG has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly. OBJECTIVES: The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines. METHODS: Fifteen elderly volunteers, aged 66-80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions. RESULTS: There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1-7 per volunteer, 39 (83% of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70% of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea, 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038 while there was no difference in other pro- or anti-inflammatory plasma cytokines. CONCLUSIONS: Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older. TRIAL REGISTRATION: ClinicalTrials.gov NCT 01274598.

  17. A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of DS-3801b, a Motilin Receptor Agonist, in Healthy Subjects.

    Science.gov (United States)

    Dennie, Justin; Atiee, George; Warren, Vance; Tao, Ben; Morimoto, Kiyoshi; Senaldi, Giorgio

    2017-09-01

    DS-3801b is an orally active, nonmacrolide, selective motilin receptor agonist. The aim of this 2-part first-in-human study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic effects on proximal and distal gastrointestinal (GI) motility of single oral doses of DS-3801b in healthy subjects. The (13) C-octanoate breath test was used to assess gastric emptying (GE), a measure of proximal GI motility. The time to first bowel movement (TTFBM) and the consistency of the first bowel movement according to the Bristol Stool Scale (BSS) were recorded to assess distal GI motility. In part A, 48 subjects received single oral doses of DS-3801b from 1 to 100 mg or placebo (6 DS-3801b, 2 placebo per cohort). In part B, 12 subjects received 50 mg of DS-3801b or placebo to assess GE. DS-3801b is safe and generally well tolerated after doses up to 50 mg, resulting in mild, predominantly GI adverse events. DS-3801a plasma concentrations increase with increasing doses; however, Cmax increases greater than dose-proportionally, whereas AUC increases less than dose-proportionally. The double peaks observed are consistent with multiple absorption sites. Results of the (13) C-octanoate breath test indicate that DS-3801b accelerates GE. Fifty milligrams of DS-3801b resulted in a 20.8% median reduction in GE T1/2 and a 20.6% median reduction in GE Tlag compared with placebo. However, this increase in proximal GI motility was not accompanied by an effect on distal GI motility, as indicated by no significant differences in TTFBM and BSS values across DS-3801b dose levels or compared with placebo. © 2017, The American College of Clinical Pharmacology.

  18. Safety, Tolerability, and Pharmacokinetic Characteristics of a Novel Nonopioid Analgesic, VVZ-149 Injections in Healthy Volunteers: A First-in-Class, First-in-Human Study.

    Science.gov (United States)

    Oh, Jaeseong; Lee, SeungHwan; Kim, Anhye; Yoon, Jangsoo; Jang, Kyungho; Lee, Doo H; Cho, Sunyoung; Lee, Sang Rim; Yu, Kyung-Sang; Chung, Jae-Yong

    2017-08-16

    VVZ-149, a dual antagonist of GlyT2 and 5HT2 A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early-stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ-149 injections in healthy male volunteers were explored in a randomized, double-blind, single- and multiple-ascending-dose (SAD and MAD, respectively), placebo-controlled clinical study. Subjects randomly received a 4-hour intravenous infusion of 0.25-8 mg/kg VVZ-149 or placebo in the SAD study (n = 46) or a 4-hour intravenous infusion of 4-7 mg/kg VVZ-149 or placebo twice daily for 3 days in the MAD study (n = 20). Serial blood and urine samples were collected for the pharmacokinetic analysis of VVZ-149 and its active metabolite (VVZ-368). Noncompartmental and compartmental pharmacokinetic analyses were performed. Various dosing scenarios were simulated to identify the adequate dosing regimen for the subsequent trials. Plasma exposure to VVZ-149 and VVZ-368 showed a dose-proportional increase. VVZ-149 did not accumulate in the plasma, whereas the plasma concentration of VVZ-368 increased by 1.23- to 2.49-fold after the fifth and sixth doses, respectively, in the MAD trial. Among the simulated dosing regimens, a loading dose followed by a maintenance dose was found to be an optimal dosing regimen, yielding the effective concentration estimated from animal studies in rat models of neuropathic or inflammatory pain. Single- or multiple-dose administration of VVZ-149 was generally well tolerated. These results showed that 0.5-8 mg/kg VVZ-149 exhibited linear pharmacokinetic characteristics and can be safely administered in further clinical studies. © 2017, The American College of Clinical Pharmacology.

  19. Normal tissue tolerance to external beam radiation therapy: The stomach; Dose de tolerance a l'irradiation des tissus sains: l'estomac

    Energy Technology Data Exchange (ETDEWEB)

    Oberdiac, P. [Service de radiotherapie, hopital de Bellevue, CHU de Saint-Etienne, 42 - Saint-Etienne (France); Mineur, L. [Unite d' oncologie digestive et radiotherapie, institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  20. Phase 1 safety, tolerability, and pharmacokinetic study of single ascending doses of XM17 (recombinant human follicle-stimulating hormone in downregulated healthy women

    Directory of Open Access Journals (Sweden)

    Lammerich A

    2015-07-01

    Full Text Available Andreas Lammerich, Peter Bias, Beate Gertz Merckle GmbH, Ulm, Germany Background: XM17 is a recombinant human follicle-stimulating hormone (follitropin alfa for stimulation of multifollicular development in women undergoing controlled ovarian hyperstimulation during assisted reproductive therapy and for treatment of anovulation. Manufactured using Chinese hamster ovary cells transfected with the human follicle-stimulating hormone gene, XM17 has an identical amino acid sequence to that of the human protein as well as to those of the other approved recombinant human follicle-stimulating hormone products. Glycosylation patterns may differ slightly between products. The objectives of this first-in-human study were to assess the safety, tolerability, pharmacokinetics, and dose-proportionality of single ascending subcutaneous doses of XM17 in healthy young female volunteers.Methods: Endogenous follicle-stimulating hormone was downregulated by implanting a 1-month depot of goserelin acetate 3.6 mg on day 0 in eligible subjects. On day 14 of the experimental period, subjects received one of four ascending doses of XM17. Blood sampling to obtain the pharmacokinetic profile of XM17 was done at frequent intervals until 168 hours post-dose.Results: Following downregulation of endogenous follicle-stimulating hormone to <4 IU/L, 40 subjects (of mean age 29±5.4 years received single subcutaneous doses of 37.5 (n=4, pilot group, 75, 150, or 300 IU (n=12 each of XM17. The mean serum concentration-time profiles of XM17 revealed dose-related increases in maximum concentration (Cmax within 24 hours followed by monoexponential decay for the three higher dose levels. Slopes estimated by linear regression for Cmax and AUC0–168h were ~1.0 (0.9052 IU/L and 1.0964 IU·h/L, respectively. For each IU of XM17 administered, Cmax and AUC0–168h rose by 0.032 IU/L and 2.60 IU·h/L, respectively. Geometric mean elimination half-life ranged from 54 to 90 hours. No antibodies

  1. Systemic exposure to armodafinil and its tolerability in healthy elderly versus young men: an open-label, multiple-dose, parallel-group study.

    Science.gov (United States)

    Darwish, Mona; Kirby, Mary; Hellriegel, Edward T; Yang, Ronghua; Robertson, Philmore

    2011-02-01

    Armodafinil (Nuvigil(®), Cephalon, Inc., Frazer, PA, USA), the longer-lasting isomer of racemic modafinil, is a nonamphetamine, wakefulness-promoting medication. In patients with excessive sleepiness associated with shift work disorder, treated obstructive sleep apnoea, or narcolepsy, armodafinil has been found to improve wakefulness throughout the shift or day. In addition, while not approved for this indication, armodafinil has been found to improve excessive sleepiness associated with jet-lag disorder. This study evaluated systemic exposure to armodafinil and its two major circulating metabolites, R-modafinil acid and modafinil sulfone, and assessed the tolerability profile of armodafinil in elderly and young subjects. The pharmacokinetics and tolerability of armodafinil were assessed in an open-label, multiple-dose, parallel-group study in two groups (n = 25 in each group) of healthy men (elderly group aged ≥65 years and young group aged 18-45 years) who received armodafinil 50 mg on day 1, 100 mg on day 2 and 150 mg once daily on days 3 through 7. Plasma concentrations of armodafinil and its metabolites were quantified over 72 hours following the last dose on day 7. Pharmacokinetic parameters, including area under the plasma drug concentration-versus-time curve during a dosing interval (AUC(τ)) and maximum observed plasma drug concentration (C(max)), and tolerability were assessed. All 50 subjects enrolled in the study were evaluable for tolerability and 49 were included in the pharmacokinetic analysis. One elderly subject was excluded from the pharmacokinetic analyses because of apparent noncompliance with armodafinil dosing. Systemic exposure following administration of armodafinil, as measured by steady-state AUC(τ) and C(max) values, was approximately 15% greater in elderly subjects compared with young subjects. Geometric mean ratios for AUC(τ) and C(max) in the two groups were 1.14 (95% CI 1.03, 1.25; p = 0.0086) and 1.15 (95% CI 1

  2. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.

    Science.gov (United States)

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-06-21

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP.

  3. A new method of infrared thermography for quantification of brown adipose tissue activation in healthy adults (TACTICAL): a randomized trial.

    Science.gov (United States)

    Ang, Qi Yan; Goh, Hui Jen; Cao, Yanpeng; Li, Yiqun; Chan, Siew-Pang; Swain, Judith L; Henry, Christiani Jeyakumar; Leow, Melvin Khee-Shing

    2017-05-01

    The ability to alter the amount and activity of brown adipose tissue (BAT) in human adults is a potential strategy to manage obesity and related metabolic disorders associated with food, drug, and environmental stimuli with BAT activating/recruiting capacity. Infrared thermography (IRT) provides a non-invasive and inexpensive alternative to the current methods (e.g. (18)F-FDG PET) used to assess BAT. We have quantified BAT activation in the cervical-supraclavicular (C-SCV) region using IRT video imaging and a novel image computational algorithm by studying C-SCV heat production in healthy young men after cold stimulation and the ingestion of capsinoids in a prospective double-blind placebo-controlled randomized trial. Subjects were divided into low-BAT and high-BAT groups based on changes in IR emissions in the C-SCV region induced by cold. The high-BAT group showed significant increases in energy expenditure, fat oxidation, and heat output in the C-SCV region post-capsinoid ingestion compared to post-placebo ingestion, but the low-BAT group did not. Based on these results, we conclude that IRT is a promising tool for quantifying BAT activity.

  4. C-reactive protein in healthy subjects: Associations with obesity, insulin resistance, and endothelial dysfunction : A potential role for cytokines originating from adipose tissue?

    NARCIS (Netherlands)

    Yudkin, J.S.; Stehouwer, C.D.A.; Emeis, J.J.; Coppack, S.W.

    1999-01-01

    C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of level

  5. The association of SNPs in Hsp90β gene 5' flanking region with thermo tolerance traits and tissue mRNA expression in two chicken breeds.

    Science.gov (United States)

    Chen, Zhuo-Yu; Gan, Jian-Kang; Xiao, Xiong; Jiang, Li-Yan; Zhang, Xi-Quan; Luo, Qing-Bin

    2013-09-01

    Thermo stress induces heat shock proteins (HSPs) expression and HSP90 family is one of them that has been reported to involve in cellular protection against heat stress. But whether there is any association of genetic variation in the Hsp90β gene in chicken with thermo tolerance is still unknown. Direct sequencing was used to detect possible SNPs in Hsp90β gene 5' flanking region in 3 chicken breeds (n = 663). Six mutations, among which 2 SNPs were chosen and genotypes were analyzed with PCR-RFLP method, were found in Hsp90β gene in these 3 chicken breeds. Association analysis indicated that SNP of C.-141G>A in the 5' flanking region of the Hsp90β gene in chicken had some effect on thermo tolerance traits, which may be a potential molecular marker of thermo tolerance, and the genotype GG was the thermo tolerance genotype. Hsp90β gene mRNA expression in different tissues detected by quantitative real-time PCR assay were demonstrated to be tissue dependent, implying that different tissues have distinct sensibilities to thermo stress. Besides, it was shown time specific and varieties differences. The expression of Hsp90β mRNA in Lingshan chickens in some tissues including heart, liver, brain and spleen were significantly higher or lower than that of White Recessive Rock (WRR). In this study, we presume that these mutations could be used in marker assisted selection for anti-heat stress chickens in our breeding program, and WRR were vulnerable to tropical thermo stress whereas Lingshan chickens were well adapted.

  6. Heart-type Fatty Acid-binding Protein Is Essential for Efficient Brown Adipose Tissue Fatty Acid Oxidation and Cold Tolerance*

    OpenAIRE

    Vergnes, Laurent; Chin, Robert; Young, Stephen G.; Reue, Karen

    2010-01-01

    Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3−/− mice exhibit ...

  7. Pharmacokinetics and Tolerability of Rufinamide Following Single and Multiple Oral Doses and Effect of Food on Pharmacokinetics in Healthy Chinese Subjects.

    Science.gov (United States)

    Xu, Mingzhen; Ni, Yang; Zhou, Ying; He, Xiaomeng; Li, Huqun; Chen, Hui; Li, Weiyong

    2016-10-01

    Rufinamide is a triazole derivative that is structurally unrelated to currently marketed antiepileptic medications for add-on treatment of seizures in the setting of Lennox-Gastaut syndrome in patients from the age of 4 years. The purpose of this study was to determine the pharmacokinetic and safety profile of single and multiple doses of rufinamide in healthy Chinese subjects. The effects of food and gender on the pharmacokinetic properties of rufinamide were also evaluated. In the single-dose study, volunteers were randomly assigned to 4 dose groups and received a single dose of 200, 400, 800, 1200 mg rufinamide tablets under fasting condition. Ten subjects in the 200-mg dose group were randomly assigned to either a high-fat or non-high-fat breakfast group in each study period. The drug administration was separated by a washout period of 7 calendar days. In the multiple-dose study, 10 subjects were administered on an empty stomach rufinamide 200 mg twice daily for 6 consecutive days. Liquid chromatography tandem mass spectrometry (LC-MS/MS) method was applied to determine plasma concentration of rufinamide. Pharmacokinetic parameters, including the maximum plasma concentration (C max), the time to peak concentration (t max), the area under the plasma concentration versus time curve from time 0 to the last measurable concentration (AUC0-t ) and from time 0 to infinity (AUC0-∞), terminal elimination half-life (t 1/2), apparent volume of distribution (V d), apparent clearance (CL), average residence time (MRT), area under the plasma concentration versus time curve from time 0 to the last measurable concentration at steady state (AUCss), peak concentration (C max,ss) and trough level concentration (C min,ss) at steady state were calculated using non-compartmental models. Tolerability was assessed based on investigator inquiries, spontaneous reports and clinical evaluations. Rufinamide displayed a dose-dependent, but sub-proportional increase in exposure

  8. Analyses of the temporal dynamics of fungal communities colonizing the healthy wood tissues of esca leaf-symptomatic and asymptomatic vines.

    Directory of Open Access Journals (Sweden)

    Emilie Bruez

    Full Text Available Esca, a Grapevine Trunk Disease (GTD, is of major concern for viticulture worldwide. Our study compares the fungal communities that inhabit the wood tissues of vines that expressed or not foliar esca-symptoms. The trunk and rootstock tissues were apparently healthy, whether the 10 year-old plants were symptomatic or not. The only difference was in the cordon, which contained white rot, a typical form of esca, in 79% of symptomatic plants. Observations over a period of one year using a fingerprint method, Single Strand Conformation Polymorphism (SSCP, and the ITS-DNA sequencing of cultivable fungi, showed that shifts occurred in the fungal communities colonizing the healthy wood tissues. However, whatever the sampling time, spring, summer, autumn or winter, the fungi colonizing the healthy tissues of asymptomatic or symptomatic plants were not significantly different. Forty-eight genera were isolated, with species of Hypocreaceae and Botryosphaeriaceae being the most abundant species. Diverse fungal assemblages, made up of potentially plant-pathogenic and -protective fungi, colonized these non-necrotic tissues. Some fungi, possibly involved in GTD, inhabited the non-necrotic wood of young plants, but no increase in necrosis areas was observed over the one-year period.

  9. Histogram-based characterization of healthy and ischemic brain tissues using multiparametric MR imaging including apparent diffusion coefficient maps and relaxometry.

    Science.gov (United States)

    Bernarding, J; Braun, J; Hohmann, J; Mansmann, U; Hoehn-Berlage, M; Stapf, C; Wolf, K J; Tolxdorff, T

    2000-01-01

    Decreased, renormalized, or increased values of the calculated apparent diffusion coefficient (ADC) are observed in stroke models. A quantitative description of corresponding tissue states using ADC values may be extended to include true relaxation times. A histogram-based segmentation is well suited for characterizing tissues according to specific parameter combinations irrespective of the heterogeneity found for human healthy and ischemic brain tissues. In a new approach, navigated diffusion-weighted images and ADC maps were incorporated into voxel-based parameter sets of relaxation times (T1, T2), and T1- or T2-weighted images, followed by a supervised histogram-based analysis. Healthy tissues were segmented by incorporating T1 relaxation into the data set, ischemic regions by combining T2- or diffusion-weighted images with ADC maps. Mean values of healthy and pathologic tissues were determined, spatial distributions of the parameter vectors were visualized using color-encoded overlays. One to six days after stroke, ischemic regions exhibited reduced relative mean ADC values.

  10. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

    Directory of Open Access Journals (Sweden)

    Park SI

    2015-02-01

    Full Text Available Sang-In Park,1,* Howard Lee,1,2,* Jaeseong Oh,1 Kyoung Soo Lim,3 In-Jin Jang,1 Jeong-Ae Kim,4 Jong Hyuk Jung,4 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Clinical Trials Center, Seoul National University Hospital, Seoul, 3Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, 4LG Life Sciences, Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Background: In type 2 diabetes mellitus, fixed-dose combination (FDC can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD, pharmacokinetic (PK, and tolerability profiles of gemigliptin and extended-release metformin (metformin XR between FDC and separate tablets.Methods: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1 and metformin XR (500 mg ×2 were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4 activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs of FDC to separate tablet formulations and their 90% confidence intervals (CIs were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study.Results: The plasma DPP-4 activity

  11. Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation.

    Science.gov (United States)

    Lin, Jeng-Yee; Tsai, Feng-Chou; Wallace, Christopher Glenn; Huang, Wei-Chao; Wei, Fu-Chan; Liao, Shuen-Kuei

    2012-11-01

    Mixed chimerism with long-term composite tissue allotransplant (CTA) acceptance can be achieved through allogeneic bone marrow transplantation (BMT). The present study investigated the optimal chimerism level by giving different irradiation dosages to recipients to induce tolerance to CTA. Chimera were prepared using Brown-Norway and Lewis rats with strong major histocompatibility complex incompatibility. The Lewis rats received 5 mg antilymphocyte globulin (day -1 and 10) and 16 mg/kg cyclosporine (day 0-10) and were separated into groups 1, 2, 3, 4, and 5 according to the day -1 irradiation dosage: 0, 200, 400, 600, and 950 cGy, respectively. The Lewis rats were then reconstituted with 100 × 10(6) T-cell-depleted Brown-Norway bone marrow cells (day 0) and received vascularized Brown-Norway-CTA on day 28. Chimerism was assessed monthly by flow cytometry starting on day 28 after BMT. Graft-versus-host disease (GVHD) was assessed clinically and histologically. Chimerism, 4 weeks after BMT, averaged 0.2%, 9.2%, 30.7%, 58%, and 99.3% in groups 1 to 5, respectively. GVHD occurred as follows: groups 1 and 2, none; group 3, 1 case of GVHD; group 4, 7 cases of GVHD (of which 3 died); and group 5, 10 cases of GVHD (of which 6 died). The percentage of long-term CTA acceptance was 0%, 0%, 90%, 70%, and 40% in groups 1 to 5, respectively. The percentage of regulatory T cells was significantly lower in high-chimerism (≥ 20%, n = 15) than in low-chimerism (<20%, n = 5) rats that accepted CTA long-term . The chimerism level correlated positively with GVHD occurrence and long-term CTA acceptance but correlated negatively with regulatory T-cell levels. Optimal chimerism for CTA acceptance through pre-CTA BMT and irradiation occurs at 20-50% at day 28 after BMT in the rat model. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Pharmacokinetics and tissue residues of norfloxacin and its N-desethyl- and oxo-metabolites in healthy pigs.

    Science.gov (United States)

    Anadón, A; Martinez-Larrañaga, M R; Diaz, M J; Fernandez, R; Martinez, M A; Fernandez, M C

    1995-06-01

    The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight. After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a tmax of 1.46 +/- 0.06 h. The elimination half-life (t1/2 beta) and the mean residence time of norfloxacin in plasma were 4.99 +/- 0.28 and 6.05 +/- 0.22 h, respectively, after i.m. administration and 3.65 +/- 0.16 and 3.34 +/- 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 +/- 4.4%. Plasma concentrations greater than 0.2 microgram/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 +/- 0.03 micrograms/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases (t1/2 alpha, t1/2 beta) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacin and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 microgram/g on day 12 after the end of dosing.

  13. Experimental hyperglycemia induces an increase of monocyte and T-lymphocyte content in adipose tissue of healthy obese women.

    Directory of Open Access Journals (Sweden)

    Michaela Tencerová

    Full Text Available Hyperglycemia represents one of possible mediators for activation of immune system and may contribute to worsening of inflammatory state associated with obesity. The aim of our study was to investigate the effect of a short-term hyperglycemia (HG on the phenotype and relative content of immune cells in circulation and subcutaneous abdominal adipose tissue (SAAT in obese women without metabolic complications.Three hour HG clamp with infusion of octreotide and control investigations with infusion of octreotide or saline were performed in three groups of obese women (Group1: HG, Group 2: Octreotide, Group 3: Saline, n=10 per group. Before and at the end of the interventions, samples of SAAT and blood were obtained. The relative content of immune cells in blood and SAAT was determined by flow cytometry. Gene expression analysis of immunity-related markers in SAAT was performed by quantitative real-time PCR.In blood, no changes in analysed immune cell population were observed in response to HG. In SAAT, HG induced an increase in the content of CD206 negative monocytes/macrophages (p<0.05 and T lymphocytes (both T helper and T cytotoxic lymphocytes, p<0.01. Further, HG promoted an increase of mRNA levels of immune response markers (CCL2, TLR4, TNFα and lymphocyte markers (CD3g, CD4, CD8a, TBX21, GATA3, FoxP3 in SAAT (p<0.05 and 0.01. Under both control infusions, none of these changes were observed.Acute HG significantly increased the content of monocytes and lymphocytes in SAAT of healthy obese women. This result suggests that the short-term HG can modulate an immune status of AT in obese subjects.

  14. Skin indentation firmness and tissue dielectric constant assessed in face, neck, and arm skin of young healthy women.

    Science.gov (United States)

    Mayrovitz, Harvey N; Corbitt, Kelly; Grammenos, Alexandra; Abello, Allen; Mammino, Jason

    2017-02-01

    Our goal was to test the hypothesis that skin firmness correlates with skin hydration. Dermal water was assessed by tissue dielectric constant (TDC) at 0.5 mm (TDC0.5 ) and 2.5 mm (TDC2.5 ) depths on four face sites and two arm sites of 35 women (25.0 ± 1.6 years). Firmness was determined by force (mN) to indent skin to 0.3 mm (F0.3 ) and 1.3 mm (F1.3 ). F0.3 was similar among face sites (avg = 16.2 ± 7.2 mN) but F1.3 varied (avg = 32.5 ± 4.1 mN). TDC2.5 was similar among face sites (avg = 37.7 ± 4.2) but TDC0.5 varied (avg = 36.2 ± 4.8). F1.3 of arm sites was similar (avg = 60.2 ± 18.6 mN) and both greater than F1.3 of neck (28.3 ± 7.1 mN) and face. Regression analysis showed a near-zero correlation between forces and TDC at all sites. The near-zero correlation may be due to low skin interstitial hydraulic resistance to mobile water movement in healthy young skin. If true, then conditions in which dermal hydraulic conductance is reduced as in lymphedematous, diabetic, or aged skin are more likely show the hypothesized relationship. Our findings provide normalized reference values and suggest that such persons are an important population to study to test for a possible skin water-indentation force relationship and its utilization for early diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: safety, tolerability, pharmacokinetics and pharmacodynamics--results from single oral dose studies in healthy volunteers.

    Science.gov (United States)

    Stoch, S Aubrey; Zajic, Stefan; Stone, Julie A; Miller, Deborah L; van Bortel, Lucas; Lasseter, Kenneth C; Pramanik, Barnali; Cilissen, Caroline; Liu, Qi; Liu, Lida; Scott, Boyd B; Panebianco, Deborah; Ding, Yu; Gottesdiener, Keith; Wagner, John A

    2013-05-01

    To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of odanacatib (ODN), a cathepsin K inhibitor, in humans. Two double-blind, randomized, placebo-controlled, single oral dose studies were performed with ODN (2-600 mg) in 44 healthy volunteers (36 men and eight postmenopausal women). Adverse experiences (AEs) with single doses of ODN were transient and mild to moderate, with the exception of one severe AE of gastroenteritis. Headache was the most frequent AE. After absorption of ODN (initial peak concentrations 4-6 h postdose), plasma concentrations exhibited a monophasic decline, with an apparent terminal half-life of ∼40-80 h. The area under the curve0-24 hours (AUC(0-24 h)), concentration at 24 hours (C(24 h)) and maximum concentration (C(max,overal)) increased in a less than dose-proportional manner from 2 to 600 mg. Administration of ODN with a high-fat meal led to ∼100% increases in AUC(0-24 h), C(max,day1), C(max,overall) and C(24 h) relative to the fasted state, while administration with a low-fat meal led to a ∼30% increase in those parameters. Reduction of biomarkers of bone resorption, the C- and N-telopeptides of cross-links of type I collagen, (CTx and NTx, respectively), was noted at 24 h for doses ≥5 mg and at 168 h postdose for ≥10 mg. In postmenopausal women administered 50 mg ODN, reductions in serum CTx of -66% and urine NTx/creatinine (uNTx/Cr) of -51% relative to placebo were observed at 24 h. At 168 h, reductions in serum CTx (-70%) and uNTx/Cr (-78%) were observed relative to baseline. Pharmacokinetic/pharmacodynamic modeling characterized the ODN concentration/uNTx/Cr relation, with a modeled EC50 value of 43.8 nM and ∼80% maximal reduction. Odanacatib was well tolerated and has a pharmacokinetic and pharmacodynamic profile suitable for once weekly dosing. © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. British Journal of

  16. Effect of caffeine on glucose tolerance of healthy adults%咖啡因对健康成人糖耐量的影响

    Institute of Scientific and Technical Information of China (English)

    梁艳; 陈充抒; 梁莉

    2011-01-01

    目的:观察口服400 mg咖啡因对正常成人糖耐量的影响.方法:采用单盲、安慰剂对照的随机临床研究.46位年龄在25~40岁的健康成人在4周观察期内需戒饮茶,咖啡,可口可乐或巧克力,并写下知情同意书.观察期结束后,随机分为两组分别服用1周咖啡因或安慰剂,进行葡萄糖耐量测试.结果:在前2h,两组受试者血糖值正常且相似,但到第3,4h,口服咖啡因组受试者与空白对照组比较,糖耐量曲线明显左移,血浆胰岛素水平略有增加.结论:健康成人口服咖啡因有降低血糖的作用,且伴有胰岛素水平轻微升高的依赖作用.%Objective; To investigate the effect of 400 mg oral caffeine on glucose tolerance. Methods; In a single-blind random clinical study, 46 healthy adults aged 25 ~40 years were treated with oral caffeine or placebo after getting their informed consents. They were abstained from coffee, tea, chocolate and cola for 4 weeks before testing. A 75 g oral glucose tolerance test (OGTT) was performed one week after taking caffeine or placebo. Results; The blood glucose curve was normal in all subjects, and was similar in the two groups until the second hour. In subjects taking caffeine, a shift in the curve towards the left was detected at the 3rd and 4th hours in comparison to those taking the placebo. Blood insulin levels were increased at 3rd and 4th hours after taking caffeine. Conclusion; Caffeine can reduce blood glucose levels in an insulin-dependent manner.

  17. Knockout of Vasohibin-1 Gene in Mice Results in Healthy Longevity with Reduced Expression of Insulin Receptor, Insulin Receptor Substrate 1, and Insulin Receptor Substrate 2 in Their White Adipose Tissue

    Science.gov (United States)

    Takeda, Eichi; Suzuki, Yasuhiro; Yamada, Tetsuya; Katagiri, Hideki

    2017-01-01

    Vasohibin-1 (Vash1), originally isolated as an endothelium-derived angiogenesis inhibitor, has a characteristic of promoting stress tolerance in endothelial cells (ECs). We therefore speculated that the lack of the vash1 gene would result in a short lifespan. However, to our surprise, vash1−/− mice lived significantly longer with a milder senescence phenotype than wild-type (WT) mice. We sought the cause of this healthy longevity and found that vash1−/− mice exhibited mild insulin resistance along with reduced expression of the insulin receptor (insr), insulin receptor substrate 1 (irs-1), and insulin receptor substrate 2 (irs-2) in their white adipose tissue (WAT) but not in their liver or skeletal muscle. The expression of vash1 dominated in the WAT among those 3 organs. Importantly, vash1−/− mice did not develop diabetes even when fed a high-fat diet. These results indicate that the expression of vash1 was required for the normal insulin sensitivity of the WAT and that the target molecules for this activity were insr, irs1, and irs2. The lack of vash1 caused mild insulin resistance without the outbreak of overt diabetes and might contribute to healthy longevity.

  18. Knockout of Vasohibin-1 Gene in Mice Results in Healthy Longevity with Reduced Expression of Insulin Receptor, Insulin Receptor Substrate 1, and Insulin Receptor Substrate 2 in Their White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Eichi Takeda

    2017-01-01

    Full Text Available Vasohibin-1 (Vash1, originally isolated as an endothelium-derived angiogenesis inhibitor, has a characteristic of promoting stress tolerance in endothelial cells (ECs. We therefore speculated that the lack of the vash1 gene would result in a short lifespan. However, to our surprise, vash1−/− mice lived significantly longer with a milder senescence phenotype than wild-type (WT mice. We sought the cause of this healthy longevity and found that vash1−/− mice exhibited mild insulin resistance along with reduced expression of the insulin receptor (insr, insulin receptor substrate 1 (irs-1, and insulin receptor substrate 2 (irs-2 in their white adipose tissue (WAT but not in their liver or skeletal muscle. The expression of vash1 dominated in the WAT among those 3 organs. Importantly, vash1−/− mice did not develop diabetes even when fed a high-fat diet. These results indicate that the expression of vash1 was required for the normal insulin sensitivity of the WAT and that the target molecules for this activity were insr, irs1, and irs2. The lack of vash1 caused mild insulin resistance without the outbreak of overt diabetes and might contribute to healthy longevity.

  19. Differential molecular responses of rice and wheat coleoptiles to anoxia reveal novel metabolic adaptations in amino acid metabolism for tissue tolerance.

    Science.gov (United States)

    Shingaki-Wells, Rachel N; Huang, Shaobai; Taylor, Nicolas L; Carroll, Adam J; Zhou, Wenxu; Millar, A Harvey

    2011-08-01

    Rice (Oryza sativa) and wheat (Triticum aestivum) are the most important starch crops in world agriculture. While both germinate with an anatomically similar coleoptile, this tissue defines the early anoxia tolerance of rice and the anoxia intolerance of wheat seedlings. We combined protein and metabolite profiling analysis to compare the differences in response to anoxia between the rice and wheat coleoptiles. Rice coleoptiles responded to anoxia dramatically, not only at the level of protein synthesis but also at the level of altered metabolite pools, while the wheat response to anoxia was slight in comparison. We found significant increases in the abundance of proteins in rice coleoptiles related to protein translation and antioxidant defense and an accumulation of a set of enzymes involved in serine, glycine, and alanine biosynthesis from glyceraldehyde-3-phosphate or pyruvate, which correlates with an observed accumulation of these amino acids in anoxic rice. We show a positive effect on wheat root anoxia tolerance by exogenous addition of these amino acids, indicating that their synthesis could be linked to rice anoxia tolerance. The potential role of amino acid biosynthesis contributing to anoxia tolerance in cells is discussed.

  20. Compositional analysis of grain and forage from MON 87427, an inducible male sterile and tissue selective glyphosate-tolerant maize product for hybrid seed production.

    Science.gov (United States)

    Venkatesh, Tyamagondlu V; Breeze, Matthew L; Liu, Kang; Harrigan, George G; Culler, Angela H

    2014-02-26

    Conventional maize hybrid seed production has historically relied upon detasseling using either manual methods or semiautomated processes to ensure the purity of the hybrid cross. Monsanto Co. has developed biotechnology-derived MON 87427 maize with tissue-selective glyphosate tolerance to facilitate the production of hybrid maize seed. MON 87427 utilizes a specific promoter and intron combination to drive expression of CP4 EPSPS protein in vegetative and female reproductive tissues, conferring tolerance to glyphosate. This specific combination of regulatory elements also results in limited or no production of CP4 EPSPS protein in two key male reproductive tissues: pollen microspores, which develop into pollen grains, and tapetum cells that supply nutrients to the pollen. Thus, MON 87427 induces a male sterile phenotype after appropriately timed glyphosate applications. To confer additional benefits of herbicide tolerance and/or insect resistance, MON 87427 was combined with MON 89034 and NK603 by conventional breeding to develop MON 87427 × MON 89034 × NK603. The work described here is an assessment of the nutrient, antinutrient, and secondary metabolite levels in grain and forage tissues of MON 87427 and MON 87427 × MON 89034 × NK603. Results demonstrated that MON 87427 is compositionally equivalent to a near-isogenic conventional comparator. Results from this analysis established that the compositional equivalence observed for the single-event product MON 87427 is extendable to the combined-trait product, MON 87427 × MON 89034 × NK603. With increasing global demand for food production, the development of more efficient seed production strategies is important to sustainable agriculture. The study reported here demonstrated that biotechnology can be applied to simplify hybrid maize seed production without affecting crop composition.

  1. Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers.

    Science.gov (United States)

    Benvenuto, Mark; Benziger, David P; Yankelev, Sara; Vigliani, Gloria

    2006-10-01

    Daptomycin, a novel lipopeptide, is bactericidal against a broad range of gram-positive strains, including methicillin- (MRSA) and vancomycin-resistant Staphylococcus aureus. Daptomycin is approved at 4 mg/kg of body weight given intravenously once daily for the treatment of complicated skin and skin structure infections and at 6 mg/kg for the treatment of S. aureus bloodstream infections (bacteremia), including right-sided endocarditis caused by methicillin-susceptible S. aureus and MRSA. The present study was designed to evaluate the multiple-dose pharmacokinetics and safety of daptomycin at doses of 6 to 12 mg/kg in healthy volunteers. Three cohorts of 12 subjects each were given daptomycin (10 mg/kg) or placebo once daily for 14 days, daptomycin (12 mg/kg) or placebo once daily for 14 days, or daptomycin (6 or 8 mg/kg) once daily for 4 days. Daptomycin produced dose-proportional increases in the area under the plasma concentration-time curve and in trough daptomycin levels and nearly dose-proportional increases in peak daptomycin concentrations. Other pharmacokinetic parameters measured on day 1 and at steady state were independent of the dose, including the half-life (approximately 8 h), weight-normalized plasma clearance (9 to 10 ml/h/kg), and volume of distribution (approximately 100 ml/kg). Plasma protein binding was 90% to 93% and was independent of the daptomycin concentration. Daptomycin did not produce electrocardiographic abnormalities or electrophysiological evidence of muscle or nerve toxicity. Daptomycin was well tolerated in subjects dosed with up to 12 mg/kg intravenously for 14 days. Doses of daptomycin higher than 6 mg/kg once daily may be considered in further studies to evaluate the safety and efficacy of daptomycin in difficult-to-treat infections.

  2. Normal tissue tolerance to external beam radiation therapy: Bladder; Dose de tolerance a l'irradiation des tissus sains: la vessie

    Energy Technology Data Exchange (ETDEWEB)

    Pointreau, Y.; Atean, I. [Service de radiotherapie Corad, centre regional universitaire de cancerologie Henry-S.-Kaplan, hopital Bretonneau-2, CHU de Tours, 37 - Tours (France); Durdux, C. [Universite Paris-Descartes, 75 - Paris (France); Service d' oncologie radiotherapie, hopital europeen Georges-Pompidou, 75 - Paris (France)

    2010-07-15

    The bladder is a hollow visco-elastic organ involved in urinary continence. In relation to its anatomical location, bladder is exposed in whole or in part to ionizing radiation in external radiotherapy or in brachytherapy of the pelvic region. The acute and late functional changes after external beam radiation consist in urinary frequency, compliance defaults and hematuria. Incidence of urinary side-effects, as well as related modalities of radiotherapy, is poorly described in the literature. Medline literature searches were performed via PubMed using the keywords -bladder - radiotherapy - toxicity - radiation cystitis - tolerability - organ at risk- to describe urinary side-effects due to radiation. Some recommendations exist on the dose constraints applied to bladder. These were mainly established from prostate radiation therapy studies but without definitive consensus. In clinical practice, dose constraints take into account clinical settings: bladder cancer which requires total bladder irradiation or others pelvic tumours (prostate, uterus) in which the bladder is considered as an organ at risk. Risks of radiation cystitis increase with total dose (above 60 Gy), bladder irradiated volume and concomitant chemo radiation. Modern techniques using conformal radiotherapy with modulated intensity will probably have beneficial impact on bladder toxicity. (authors)

  3. Normal tissue tolerance to external beam radiation therapy: Esophagus; Dose de tolerance a l'irradiation des tissus sains: l'oesophage

    Energy Technology Data Exchange (ETDEWEB)

    Bera, G.; Pointreau, Y. [Clinique d' oncologie-radiotherapie, centre Henry-S.-Kaplan, hopital Bretonneau, CHU de Tours, 37 - Tours (France); Denis, F.; Dupuis, O. [Centre Jean-Bernard, clinique Victor-Hugo, 72 - Le-Mans (France); Orain, I. [Service d' anatomie et cytologie pathologiques, hopital Trousseau, CHU de Tours, 37 - Tours (France); Crehange, G. [Departement de radiotherapie, centre Georges-Francois-Leclerc, 21 - Dijon (France)

    2010-07-15

    The esophagus is a musculo-membranous tube through which food passes from the pharynx to the stomach. Due to its anatomical location, it can be exposed to ionizing radiation in many external radiotherapy indications. Radiation-induced esophageal mucositis is clinically revealed by dysphagia and odynophagia, and usually begins 3 to 4 weeks after the start of radiation treatment. With the rise of multimodality treatments (e.g., concurrent chemoradiotherapy, dose escalation and accelerated fractionation schemes), esophageal toxicity has become a significant dose-limiting issue. Understanding the predictive factors of esophageal injury may improve the optimal delivery of treatment plans. It may help to minimize the risks, hence increasing the therapeutic ratio. Based on a large literature review, our study describes both early and late radiation-induced esophageal injuries and highlights some of the predictive factors for cervical and thoracic esophagus toxicity. These clinical and dosimetric parameters are numerous but none is consensual. The large number of dosimetric parameters strengthens the need of an overall analysis of the dose/volume histograms. The data provided is insufficient to recommend their routine use to prevent radiation-induced esophagitis. Defining guidelines for the tolerance of the esophagus to ionizing radiation remains essential for a safe and efficient treatment. (authors)

  4. Normal tissue tolerance to external beam radiation therapy: Liver; Dose de tolerance a l'irradiation des tissus sains: le foie

    Energy Technology Data Exchange (ETDEWEB)

    De Bari, B.; Mornex, F. [Departement de radiotherapie-oncologie, centre hospitalier Lyon-Sud, Universite Claude-Bernard Lyon 1 et EA3738, 69 - Pierre-Benite (France); Pointreau, Y. [Service de radiotherapie, hopital Bretonneau, CHU de Tours, centre regional universitaire de cancerologie Henry-S.-Kaplan, 37 - Tours (France); Rio, E. [Service de radiotherapie, centre regional de lutte contre le cancer Nantes-Atlantique, 44 - Saint-Herblain (France); Mirabel, X. [Centre Oscar-Lambret, 59 - Lille (France)

    2010-07-15

    The liver is a large abdominal organ in the right hypondrium. Because of its anatomical situation, it is near many abdominal PTVs as well as some lower thoracic PVTs. The liver could also be at the same time the target (for irradiation of liver metastases or primary liver tumours) and organ at risk (OAR). Radiation-induced liver disease (RILD) is radio-biologically the normal tissue complication probability (NTCP), i.e., the clinical event limiting the total dose that could be delivered. This review describes radiobiological criteria justifying the NTCP data, and recommendations for conformal 3D radiotherapy and stereotactic liver irradiation. (authors)

  5. Pilot study to visualise and measure skin tissue oxygenation, erythema, total haemoglobin and melanin content using index maps in healthy controls

    Science.gov (United States)

    Poxon, Ian; Wilkinson, Jack; Herrick, Ariane; Dickinson, Mark; Murray, Andrea

    2014-02-01

    We report on a method for analysing multispectral images of skin in vivo for the measurement and visualisation of skin characteristics. Four different indices were used to characterise skin tissue oxygenation, erythema, total haemoglobin and melanin content. Index values were calculated pixel-wise and combined to create index maps to visualise skin properties. Quantitative measurement of tissue oxygenation saturation was possible by calibrating the oxygenation index using a commercial, calibrated oximeter. Index maps were tested by arterial occlusion of the index finger with multispectral images taken before, during and after occlusion in a pilot study with 10 healthy controls.

  6. Use of macroporous gelatine spheres as a biodegradable scaffold for guided tissue regeneration of healthy dermis in humans: an in vivo study.

    Science.gov (United States)

    Huss, Fredrik R M; Nyman, Erika; Bolin, Johanna S C; Kratz, Gunnar

    2010-05-01

    If a biodegradable scaffold is applied, the dermis can be regenerated by guided tissue regeneration. Scaffolds can stimulate in-growth of cells from the surroundings that migrate into them and start to produce autologous extracellular matrix as the scaffold is degraded. Several materials are available, but most of them are in the form of sheets and need to be laid on an open wound surface. A number of injectable fillers have been developed to correct soft-tissue defects. However, none of these has been used for guided tissue regeneration. We present a new technique that could possibly be used to correct dermal defects by using macroporous gelatine spheres as a biodegradable scaffold for guided tissue regeneration. In eight healthy volunteers, intradermal injections of macroporous gelatine spheres were compared with injections of saline and hyaluronic acid (Restylane). Full-thickness skin biopsy specimens of the implants and surrounding tissue were removed 2, 8, 12 and 26 weeks after injection, and the (immuno)histological results were analysed. The Restylane merely occupied space. It shattered the dermal tissue and compressed collagen fibres and cells at the interface between the implant and the dermis. No regeneration of tissue was found with this material at any time. The macroporous gelatine spheres were populated with fibroblasts already after 2 weeks. After 8 weeks the spheres were completely populated by fibroblasts producing dermal tissue. After 12 and 26 weeks, the gelatine spheres had been more or less completely resorbed and replaced by vascularised neodermis. There were no signs of capsular formation, rejection or adverse events in any subject. Further in vivo studies in humans are needed to evaluate the effect of the macroporous spheres fully as a matrix for guided tissue regeneration with and without cellular pre-seeding. However, the results of this study indicate the possibility of using macroporous gelatine spheres as an injectable, three

  7. Assessment of the tolerability profile of an ophthalmic solution of 5% glycyrrhizin and copolymer PEG/PPG on healthy volunteers and evaluation of its efficacy in the treatment of moderate to severe blepharitis

    Directory of Open Access Journals (Sweden)

    Mencucci R

    2013-07-01

    Full Text Available Rita Mencucci, Eleonora Favuzza, Ugo MenchiniDepartment of Surgery and Translational Medicine – Eye Clinic, University of Florence, Florence, ItalyPurpose: To evaluate the tolerability on healthy volunteers and the efficacy on subjects affected by chronic moderate/severe blepharitis of a 5% glycyrrhizin and copolymer poly(ethylene glycol/poly(propylene glycol(PEG/PPG ophthalmic solution.Methods: The study was a randomized, controlled, open label, intra-patient monocentric study. It consisted of two different phases, the assessment of tolerability phase on 20 healthy volunteers, and the evaluation of the efficacy on 21 subjects affected by chronic moderate/severe blepharitis; the treatment period was 2 weeks, followed by 1-week of follow-up. In the efficacy phase, in both eyes, eyelid hygiene was also performed. At day 0, 3, 7, 14, and 21 a complete ophthalmological examination was performed. In the tolerability phase, signs of clinical toxicity were recorded and subject-reported symptoms were collected using a questionnaire. In the efficacy phase, global signs and symptoms of blepharitis scores were collected using standardized photographic scales and questionnaire. The statistical analysis was performed using the Wilcoxon signed-rank test. Results: No ocular signs of drug toxicity were reported. During the treatment period for tolerability phase, there were statistically significant higher scores of tearing and ocular discomfort in the tolerability study group versus the tolerability control group. In the efficacy phase, differences between global scores of the two groups were statistically significant at day 0 (score of the efficacy study group was higher than the efficacy control group; P = 0.005 and at day 21 (score of the efficacy study group was lower than the efficacy control group (P ≤ 0.001.The difference of global scores at day 3, 7, 14, and 21 versus day 0 was statistically significant in both groups. No serious adverse events

  8. Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues

    Directory of Open Access Journals (Sweden)

    Jenny Chun-Yee Ng

    2015-10-01

    Full Text Available Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA or coral tumors are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch’s postulates in efforts to understand the etiology and progression of SGA.

  9. Comparison of the antiseptic efficacy of tissue-tolerable plasma and an octenidine hydrochloride-based wound antiseptic on human skin.

    Science.gov (United States)

    Lademann, J; Richter, H; Schanzer, S; Patzelt, A; Thiede, G; Kramer, A; Weltmann, K-D; Hartmann, B; Lange-Asschenfeldt, B

    2012-01-01

    Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area. Copyright © 2012 S. Karger AG, Basel.

  10. Comparative Analyses of Tomato yellow leaf curl virus C4 Protein-Interacting Host Proteins in Healthy and Infected Tomato Tissues

    Directory of Open Access Journals (Sweden)

    Namgyu Kim

    2016-10-01

    Full Text Available Tomato yellow leaf curl virus (TYLCV, a member of the genus Begomovirus, is one of the most important viruses of cultivated tomatoes worldwide, mainly causing yellowing and curling of leaves with stunting in plants. TYLCV causes severe problems in sub-tropical and tropical countries, as well as in Korea. However, the mechanism of TYLCV infection remains unclear, although the function of each viral component has been identified. TYLCV C4 codes for a small protein involved in various cellular functions, including symptom determination, gene silencing, viral movement, and induction of the plant defense response. In this study, through yeast-two hybrid screenings, we identified TYLCV C4-interacting host proteins from both healthy and symptom-exhibiting tomato tissues, to determine the role of TYLCV C4 proteins in the infection processes. Comparative analyses of 28 proteins from healthy tissues and 36 from infected tissues showing interactions with TYLCV C4 indicated that TYLCV C4 mainly interacts with host proteins involved in translation, ubiquitination, and plant defense, and most interacting proteins differed between the two tissues but belong to similar molecular functional categories. Four proteins—two ribosomal proteins, S-adenosyl-L-homocysteine hydrolase, and 14-3-3 family protein—were detected in both tissues. Furthermore, the identified proteins in symptom-exhibiting tissues showed greater involvement in plant defenses. Some are key regulators, such as receptor-like kinases and pathogenesis-related proteins, of plant defenses. Thus, TYLCV C4 may contribute to the suppression of host defense during TYLCV infection and be involved in ubiquitination for viral infection.

  11. Heart-type fatty acid-binding protein is essential for efficient brown adipose tissue fatty acid oxidation and cold tolerance.

    Science.gov (United States)

    Vergnes, Laurent; Chin, Robert; Young, Stephen G; Reue, Karen

    2011-01-07

    Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3(-/-) mice exhibit extreme cold sensitivity despite induction of uncoupling and oxidative genes and hydrolysis of brown adipose tissue lipid stores. However, using FABP3 gain- and loss-of-function approaches in brown adipocytes, we detected a correlation between FABP3 levels and the utilization of exogenous fatty acids. Thus, Fabp3(-/-) brown adipocytes fail to oxidize exogenously supplied fatty acids, whereas enhanced Fabp3 expression promotes more efficient oxidation. These results suggest that FABP3 levels are a determinant of fatty acid oxidation efficiency by brown adipose tissue and that FABP3 represents a potential target for modulation of energy dissipation.

  12. Impact of physical inactivity on subcutaneous adipose tissue metabolism in healthy young male offspring of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Sonne, MP; Alibegovic, AC

    2010-01-01

    . The best known environmental modifiable risk factors for type 2 diabetes are obesity and a low level of habitual physical activity (1). Even though there is substantial evidence that a change toward a healthy lifestyle halts the progression of type 2 diabetes (2), certain groups, including first...

  13. New application of a subcellular fractionation method to kidney and testis for the determination of conjugated linoleic acid in selected cell organelles of healthy and cancerous human tissues.

    Science.gov (United States)

    Hoffmann, Kristina; Blaudszun, Jörg; Brunken, Claus; Höpker, Wilhelm-Wolfgang; Tauber, Roland; Steinhart, Hans

    2005-03-01

    To clarify the mechanism of the anticarcinogenic effect of conjugated linoleic acid (CLA), its intracellular distribution needs to be determined. Subcellular fractionation using centrifugation techniques is a method that is frequently used for isolation of cell organelles from different tissues. But as the size and density of the organelles differ, the method needs to be optimised for every type of tissue. The novelty of this study is the application of a subcellular fractionation method to human healthy and cancerous renal and testicular tissue. Separation of total tissue homogenate into nuclei, cytosol, and a mixture of mitochondria and plasma membranes was achieved by differential centrifugation. As mitochondria and plasma membranes seemed to be too similar in size and weight to be separated by differential centrifugation, discontinuous density-gradient centrifugation was carried out successfully. The purity of the subcellular fractions was checked by measuring the activity of marker enzymes. All fractions were highly enriched in their corresponding marker enzyme. However, the nuclear fractions of kidney and renal cell carcinoma were slightly contaminated with mitochondria and plasma membrane fractions of all tissues with lysosomes. The fraction designated the cytosolic fraction contained not only cytosol, but also microsomes and lysosomes. The CLA contents of the subcellular fractions were in the range 0.13-0.37% of total fatty acids and were lowest in the plasma membrane fractions of all types of tissue studied. C16:0, C18:0, C18:1 c9, C18:2 n-6, and C20:4 n-6 were found to be the major fatty acids in all the subcellular fractions studied. However, marked variations in fatty acid content between subcellular fractions and between types of tissue were detectable. Because of these differences between tissues, no general statement on characteristic fatty acid profiles of single subcellular fractions is possible.

  14. Risk assessment tool for incontinence-associated dermatitis in elderly patients combining tissue tolerance and perineal environment predictors: a prospective clinical study

    Directory of Open Access Journals (Sweden)

    Ichikawa-Shigeta Y

    2014-10-01

    Full Text Available Yoshie Ichikawa-Shigeta,1 Hiromi Sanada,2 Chizuko Konya,3 Saldy Yusuf,1 Supriadi,1 Junko Sugama11Department of Clinical Nursing, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan; 2Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; 3Department of Adult Nursing, Kanazawa Medical University, Ishikawa, JapanBackground: Elderly patients with incontinence are at risk of developing incontinence-associated dermatitis (IAD. Although perineal risk factors of IAD have been identified, the contribution of tissue tolerance to IAD remains poorly understood.Objective: This study aimed to identify predictors of IAD development in three categories of potential risk factors: perineal environment, tissue tolerance, and toileting ability.Methods: This was a prospective clinical study, conducted at a long-term medical facility in Japan between November 2011 and April 2012. The subjects were elderly female patients with urine and/or fecal incontinence, and constantly wearing absorbent products. The patients were monitored during 42 days for the onset of IAD and the emergence of potential risk factors of IAD related to tissue tolerance (skin hydration status, maceration, erythema index [EI], etc, perineal environment (urination, stool properties, etc, and toileting ability (mobility and cognitive awareness. The risk factors were identified by univariate and multiple logistic regression analysis. Receiver operating characteristic (ROC curve analysis was conducted to evaluate the predictive validity of the risk factors.Results: Among the 46 patients enrolled, IAD developed in 25 (54.3%. The factors significantly associated with IAD development were loose or liquid stools (odds ratio [OR]: 20.612, 95% confidence interval [CI]: 1.118–379.852, P=0.042, malodorous urine (OR: 37.094, 95% CI: 3.480–395.399, P=0.003, and EI ≥46 (OR: 35.191, 95% CI: 5

  15. Tissue-level leaf toughness, but not lamina thickness, predicts sapling leaf lifespan and shade tolerance of tropical tree species

    NARCIS (Netherlands)

    Kitajima, K.; Poorter, L.

    2010-01-01

    Leaf toughness is thought to enhance physical defense and leaf lifespan. Here, we evaluated the relative importance of tissue-level leaf traits vs lamina thickness, as well as their ontogenetic changes, for structure-level leaf toughness and regeneration ecology of 19 tropical tree species. We

  16. Increased lipolysis but diminished gene expression of lipases in subcutaneous adipose tissue of healthy young males with intrauterine growth retardation

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Alibegovic, Amra C; Sonne, Mette P

    2011-01-01

    ) and femoral (SCFAT) adipose tissue. Additionally, mRNA expression of lipases was evaluated in biopsies from SCAAT. Lipolysis in SCAAT was substantially higher in IUGR than in CON subjects despite markedly lower mRNA expression of lipases. Blood flow was higher in IUGR compared with CON in both SCAAT and SCFAT...... are characterized by increased in vivo adipose tissue lipolysis and blood flow with a paradoxically decreased expression of lipases compared with CON, and 10 days of physical inactivity underlined the baseline findings. Subjects with IUGR exhibit primary defects in adipose tissue metabolism........ Whole body insulin sensitivity did not differ between groups and decreased after bed rest. After bed rest, SCAAT lipolysis remained higher in IUGR compared with CON, and SCFAT lipolysis decreased in CON but not in IUGR. Prior to the development of whole body insulin resistance, young men with IUGR...

  17. Dietary boron intake does not change the ischemic tolerance and preconditioning response in isoproterenol-induced myocardial injury in healthy rats

    OpenAIRE

    Karakaş, Mehmet Fatih; Kurt, Mustafa; ARSLANTAŞ, Uğur; İpek, Göktürk; Karakaş, Esra; BİLEN, Emine; Erdamar, Hüsamettin

    2011-01-01

    Boron is important for many enzymes, most of which also have a role in the ischemic tolerance of the myocardium. We aimed to evaluate the influence of dietary boron intake on ischemic tolerance in a rat model. Materials and methods: Rats were divided into 3 groups according to the ischemia protocol: Sham (S) (n = 20 total), ischemia only (Isc-only) (n = 40 total), and remote ischemic preconditioning + ischemia (RIPC+Isc) (n = 40 total) groups. These 3 groups were further divided into 4 accor...

  18. Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment.

    Science.gov (United States)

    Melgar-Lesmes, Pedro; Balcells, Mercedes; Edelman, Elazer R

    2017-07-01

    Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment. Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op. Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment. Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. A diet enriched with Mugil cephalus processed roes modulates the tissue lipid profile in healthy rats: a biochemical and chemometric assessment.

    Science.gov (United States)

    Rosa, A; Atzeri, A; Putzu, D; Scano, P

    2016-01-01

    The effect of a diet enriched with mullet bottarga on the lipid profile (total lipids, total cholesterol, unsaturated fatty acids, α-tocopherol, and hydroperoxides) of plasma, liver, kidney, brain, and perirenal adipose tissues of healthy rats was investigated. Rats fed a 10% bottarga enriched-diet for 5 days showed body weights and tissue total lipid and cholesterol levels similar to those of animals fed control diet. Univariate and multivariate results showed that bottarga enriched-diet modified the fatty acid profile in all tissues, except brain. Significant increases of n-3 PUFA, particularly EPA, were observed together with a 20:4 n-6 decrease in plasma, liver, and kidney. Perirenal adipose tissue showed a fat accumulation that reflected the diet composition. The overall data suggest that mullet bottarga may be considered as a natural bioavailable source of n-3 PUFA and qualify it as a traditional food product with functional properties and a potential functional ingredient for preparation of n-3 PUFA enriched foods.

  20. Determinants and Regression Equations for the Calculation of z Scores of Left Ventricular Tissue Doppler Longitudinal Indexes in a Healthy Italian Pediatric Population

    Directory of Open Access Journals (Sweden)

    Veronica Fibbi

    2015-01-01

    Full Text Available Aim. We investigated the predictors of tissue Doppler left ventricular (LV longitudinal indexes in a healthy Italian pediatric population and established normative data and regression equations for the calculation of z scores. Methods and Results. A total of 369 healthy subjects aged 1–17 years (age of 6.4 ± 1.1 years, 49.1% female underwent echocardiography. LV peak longitudinal velocity at systole (s', early diastole (e', and late diastole (a' was determined by tissue Doppler. The ratio of peak early diastolic LV filling velocity to e' was calculated. Age was the only independent determinant of s' (β=0.491, p<0.0001 and the strongest determinant of e' (β=0.334, p<0.0001 and E/e' (β=-0.369, p<0.0001. Heart rate was the main determinant of a' (β=0.265, p<0.0001. Male gender showed no effects except for a weak association with lateral s', suggesting no need of gender-specific reference ranges. Age-specific reference ranges, regression equations, and scatterplots for the calculation of z scores were determined for each index. Conclusion. In a pediatric Italian population, age was the strongest determinant of LV longitudinal dynamics. The availability of age-specific normality data for the calculation of z scores may allow for correctly detecting LV dysfunction in pediatric pathological populations.

  1. c-Jun, Fra-2, and ATF-2 immunoreactivity in the jejunal tissues of the healthy rat.

    Science.gov (United States)

    Keklikoglu, Nurullah

    2008-10-01

    The aim of this study was to compare the localization of some activator protein-1 (AP-1) proteins in healthy rat jejunum. For this purpose, the AP-1 members c-Jun, Fra-2, and ATF-2 immunoreactivity (c-Jun-IR, Fra-2-IR, ATF-2-IR) in villus epithelial cells (ECs), intravillous lamina propria cells (LPCs), crypt cells (CCs), and smooth muscle cells (SMCs) were analyzed by immunohistochemical methods. Among all the cell groups, the lowest positivity ratio was found in c-Jun-IR and the highest positivity ratio was found in ATF-2-IR. For each group of ECs, LPCs, CCs, and SMCs, c-Jun-IR, Fra-2-IR, and ATF-2-IR were compared and statistically significant differences found. There were no significant differences among the cell groups with respect to c-Jun-IR and Fra-2-IR, but there was a statistically significant difference in ATF-2-IR. These findings suggest that each member of AP-1 is expressed differently and that ATF-2 is more active than c-Jun and Fra-2 in physiological conditions in healthy rat jejunum.

  2. Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota

    DEFF Research Database (Denmark)

    Elison, Emma; Vigsnæs, Louise K.; Rindom Krogsgaard, Laura

    2016-01-01

    in relative abundance of Actinobacteria and Bifidobacterium in particular and a reduction in relative abundance of Firmicutes and Proteobacteria. This study provides the first set of data on safety, tolerance and impact of HMO on the adult gut microbiota. Collectively, the results from this study show...

  3. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast

    DEFF Research Database (Denmark)

    Nilsson, A.C.; Ostman, E.M.; Holst, Jens Juul

    2008-01-01

    based bread (ordinary, high-amylose- or beta-glucan-rich genotypes) or an evening meal with white wheat flour bread (WWB) enriched with a mixture of barley fiber and resistant starch improved glucose tolerance at the subsequent breakfast compared with unsupplemented WWB (P

  4. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Science.gov (United States)

    Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang

    2016-01-01

    Background A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. Conclusion An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate

  5. Tolerating Zero Tolerance?

    Science.gov (United States)

    Moore, Brian N.

    2010-01-01

    The concept of zero tolerance dates back to the mid-1990s when New Jersey was creating laws to address nuisance crimes in communities. The main goal of these neighborhood crime policies was to have zero tolerance for petty crime such as graffiti or littering so as to keep more serious crimes from occurring. Next came the war on drugs. In federal…

  6. Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'.

    Science.gov (United States)

    Simpson, Elizabeth

    2015-04-19

    'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

  7. Molecular characterization of Staphylococcus aureus isolates from skin and soft tissue infections samples and healthy carriers in the Central Slovenia region.

    Science.gov (United States)

    Svent-Kucina, Natasa; Pirs, Mateja; Kofol, Romina; Blagus, Rok; Smrke, Dragica Maja; Bilban, Marjan; Seme, Katja

    2016-04-01

    Staphylococcus aureus is among the most important human pathogens. It is associated with different infections and is a major cause of skin and soft tissue infections (SSTIs). The aim of our study was to compare S. aureus isolates associated with SSTIs with isolates obtained from healthy carriers in the Central Slovenia region in terms of antimicrobial susceptibility, genetic diversity by clonal complex (CC)/sequence type, spa type, and by toxin gene profiling. In total, 274 S. aureus isolates were collected prospectively by culturing wound samples from 461 SSTI patients and nasal samples from 451 healthy carriers. We have demonstrated high heterogeneity in terms of CCs and spa type in both groups of isolates. The main clone among SSTI strains was Panton-Valentine leukocidin gene (pvl) positive CC121, whereas the main clone among carrier strains was CC45 carrying a large range of toxin genes. The main spa type in both groups was t091. Pvl was more frequently present in SSTI strains (31.2% SSTI vs 3.6% carrier strains) and staphylococcal enterotoxin C was more frequently present in carrier strains (1.6% SSTI vs 17.0% carrier strains). We have also demonstrated that methicillin-resistant S. aureus was a rare cause (2.8%) of SSTIs in our region.

  8. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

    Science.gov (United States)

    Thomas, Sushma S; Makar, Karen W; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y; Lampe, Paul D; Yan, Min; Markowitz, Sanford D; Bigler, Jeannette; Lampe, Johanna W; Potter, John D

    2015-12-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) - accession number GSE71571 - was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]).

  9. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial

    Directory of Open Access Journals (Sweden)

    Sushma S. Thomas

    2015-12-01

    Full Text Available Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133+2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2 levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO – accession number GSE71571 – was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9].

  10. A system model of the effects of exercise on plasma Interleukin-6 dynamics in healthy individuals: Role of skeletal muscle and adipose tissue.

    Science.gov (United States)

    Morettini, Micaela; Palumbo, Maria Concetta; Sacchetti, Massimo; Castiglione, Filippo; Mazzà, Claudia

    2017-01-01

    Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (definition of more tailored interventions for the treatment of type 2 diabetes.

  11. Constitutive expression of a barley Fe phytosiderophore transporter increases alkaline soil tolerance and results in iron partitioning between vegetative and storage tissues under stress.

    Science.gov (United States)

    Gómez-Galera, Sonia; Sudhakar, Duraialagaraja; Pelacho, Ana M; Capell, Teresa; Christou, Paul

    2012-04-01

    Cereals have evolved chelation systems to mobilize insoluble iron in the soil, but in rice this process is rather inefficient, making the crop highly susceptible to alkaline soils. We therefore engineered rice to express the barley iron-phytosiderophore transporter (HvYS1), which enables barley plants to take up iron from alkaline soils. A representative transgenic rice line was grown in standard (pH 5.5) or alkaline soil (pH 8.5) to evaluate alkaline tolerance and iron mobilization. Transgenic plants developed secondary tillers and set seeds when grown in standard soil although iron concentration remained similar in leaves and seeds compared to wild type. However, when grown in alkaline soil transgenic plants exhibited enhanced growth, yield and iron concentration in leaves compared to the wild type plants which were severely stunted. Transgenic plants took up iron more efficiently from alkaline soil compared to wild type, indicating an enhanced capacity to increase iron mobility ex situ. Interestingly, all the additional iron accumulated in vegetative tissues, i.e. there was no difference in iron concentration in the seeds of wild type and transgenic plants. Our data suggest that iron uptake from the rhizosphere can be enhanced through expression of HvYS1 and confirm the operation of a partitioning mechanism that diverts iron to leaves rather than seeds, under stress.

  12. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    Science.gov (United States)

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation.

  13. Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

    Science.gov (United States)

    Sarsby, Joscelyn; Martin, Nicholas J.; Lalor, Patricia F.; Bunch, Josephine; Cooper, Helen J.

    2014-09-01

    Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

  14. Top-down and bottom-up identification of proteins by liquid extraction surface analysis mass spectrometry of healthy and diseased human liver tissue.

    Science.gov (United States)

    Sarsby, Joscelyn; Martin, Nicholas J; Lalor, Patricia F; Bunch, Josephine; Cooper, Helen J

    2014-11-01

    Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

  15. Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome

    DEFF Research Database (Denmark)

    Leder, Lena; Kolehmainen, Marjukka; Narverud, Ingunn;

    2016-01-01

    BACKGROUND: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism...... protocol. In this sub-study, we included subjects (n = 89) from three Nordic centers: Kuopio (n = 26), Lund (n = 30), and Oulu (n = 33) with a maximum weight change of ±4 kg, high-sensitivity C-reactive protein concentration ≤10 mg L(-1), and baseline body mass index ..., and the mRNA gene expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. RESULTS: The healthy ND significantly down-regulated the expression...

  16. Comparative studies of gastrointestinal tolerance and acceptability of milk chocolate containing either sucrose, isomalt or sorbitol in healthy consumers and type II diabetics.

    Science.gov (United States)

    Zumbé, A; Brinkworth, R A

    1992-03-01

    The objective was to compare reaction of adult consumers of confectionery to milk chocolate made with either isomalt, sucrose or sorbitol. Test chocolate was eaten by subjects at home during 7 days in amounts chosen by them up to a maximum of 100 g per day. In a double-blind crossover trial isomalt chocolate was associated in healthy consumers (n = 58) with increased motion frequency, wind and flatulence compared with sucrose chocolate. However, the intensity of these gastrointestinal effects was predominantly slight and insufficient to affect acceptability. In separate crossover trials, reactions of Type II diabetic consumers to eating isomalt chocolate (n = 53) or sorbitol chocolate (n = 51) were compared to reactions when eating no chocolate. Both isomalt and sorbitol chocolate were associated with higher incidence of wind and flatulence than for no chocolate, but only sorbitol chocolate increased motion frequency. Again intensity of gastrointestinal effects was slight. It is concluded that isomalt has potential use in both regular and diabetic chocolate.

  17. Efficiency Evaluation of Five-Phase Outer-Rotor Fault-Tolerant BLDC Drives under Healthy and Open-Circuit Faulty Conditions

    Directory of Open Access Journals (Sweden)

    ARASHLOO, R. S.

    2014-05-01

    Full Text Available Fault tolerant motor drives are an interesting subject for many applications such as automotive industries and wind power generation. Among different configurations of these systems, five-phase BLDC drives are gaining more importance which is because of their compactness and high efficiency. Due to replacement of field windings by permanent magnets in their rotor structure, the main sources of power losses in these drives are iron (core losses, copper (winding losses, and inverter unit (semiconductor losses. Although low amplitude of power losses in five-phase BLDC drives is an important aspect for many applications, but their efficiency under faulty conditions is not considered in previous studies. In this paper, the efficiency of an outer-rotor five phase BLDC drive is evaluated under normal and different faulty conditions. Open-circuit fault is considered for one, two adjacent and two non-adjacent faulty phases. Iron core losses are calculated via FEM simulations in Flux-Cedrat software, and moreover, inverter losses and winding copper losses are simulated in MATLAB� environment. Experimental evaluations are conducted to evaluate the efficiency of the entire BLDC drive which verifies the theoretical developments.

  18. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Directory of Open Access Journals (Sweden)

    Choi Y

    2016-09-01

    Full Text Available YoonJung Choi,1 SeungHwan Lee,2 Sang-Min Cho,3 Won-Ho Kang,3 Kyu-Yeol Nam,4 In-Jin Jang,1 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, 2Clinical Trials Center, Seoul National University Hospital, 3Research Institute, 4Global R&D, Korea United Pharm Inc., Seoul, Republic of Korea Background: A fixed-dose combination (FDC of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods: A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results: The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94-1.01 and 0.97 (0.93-1.01, respectively. The corresponding values for losartan were 0.91 (0.81-1.02 and 1.05 (0.98-1.12, respectively. The incidence of adverse events was not significantly different between the two

  19. TU-F-CAMPUS-T-01: Potential of Using Cerium Oxide Nanoparticles (CONP) for Protecting Healthy Tissue During Accelerated Partial Breast Irradiation (APBI)

    Energy Technology Data Exchange (ETDEWEB)

    Mainali, M [University of Massachusetts Boston/Dana Farber cancer institute, Boston, MA (United States); Ngwa, W [Harvard Medical School, Boston, MA (United States); Cifter, G [University of Massachusetts Lowell/ Dana Farber cancer institute, Boston, MA (United States); Celli, J [University of Massachusetts Boston, Boston, MA (United States)

    2015-06-15

    Purpose: The purpose of this research is to investigate the feasibility of using targeted cerium oxide nanoparticles (CONP) during APBI to protect healthy cells. Methods: In one approach, CONP are assumed to be incorporated in a micrometer-thick polymer film on the surface of routinely used mammosite balloon applicators for sustained in-situ release of the CONP. In case two, CONPs are administered directly into the lumpectomy cavity. The concentration of H{sub 2}O{sub 2} produced by ionizing radiation was estimated from previously published work using short range linear extrapolation. The assessment of CONPs concentration required to absorb corresponding H{sub 2}O{sub 2} to protect healthy tissue was calculated. Fick’s Second law of diffusion was employed to determine the initial concentration of CONP needed to achieve the minimum concentration for radioprotection at distance 1 cm and 2 cm from the lumpectomy cavity during APBI. The study was carried out for different nanoparticle sizes. Results: The initial concentration of CONPs required to get desired radioprotection concentration at 1 cm and 2 cm after 7 days was found to be 0.4089 mg per Kg and 59.7605 g per Kg respectively for 2 nm size nanoparticles. Using concentrations of 5 mg per kg of CONP that have been shown to be used to confer radioprotection (for about 7.97 Gy) in experiments it was observed that 4.5631, 8.5286, 10.9247, 22.0408, 43.6796 and 65.5618 number of days are required to achieve radioprotection at 1 cm for CONP of sizes 2 nm, 3.8 nm, 5 nm, 10 nm, 20 nm, 30 nm, respectively. Conclusion: Our preliminary results show that smaller size (2 nm and 3.8 nm) CONP would be suitable as radio protectant during APBI because they took a reasonable number of days, i.e. less than 10 days to reach tissues of 1 cm or 2 cm thickness.

  20. Comparative pharmacokinetics and tolerability of branded etanercept (25 mg) and its biosimilar (25 mg): a randomized, open-label, single-dose, two-sequence, crossover study in healthy Korean male volunteers.

    Science.gov (United States)

    Gu, Namyi; Yi, Sojeong; Kim, Tae-Eun; Kim, Jaewoo; Shin, Sang-Goo; Jang, In-Jin; Yu, Kyung-Sang

    2011-12-01

    The biosimilar is a recombinant dimeric tumor necrosis factor receptor (TNFR) under development for the treatment of rheumatoid arthritis. The aim of this study was to compare the pharmacokinetics and/or tolerability of branded etanercept and its biosimilar in healthy Korean men before investigating the clinical efficacy of the biosimilar in subjects. Etanercept (reference, 25 mg) or its biosimilar (test, 25 mg) was subcutaneously injected to the periumbilical area of healthy volunteers in a randomized, open-label, single-dose, active-controlled, two-sequence, crossover study. Plasma concentrations of TNFR in serial blood samples for 480 hours after dosing were measured by ELISA. The primary outcome, pharmacokinetic characteristics, was assessed via geometric mean ratios (GMRs) of the log-transformed pharmacokinetic parameters. The second outcome, tolerability, was evaluated using physical examinations, electrocardiograms, clinical laboratory tests, vital sign measurements, and adverse events (AEs) by unmasked investigators. Twenty-three men of mean age (%CV) 25.8 years (17.1%) and weight 70.5 kg (12.8%) were administered study medication. Four subjects dropped out after the first period; their data were included in the analysis. Both test and reference drugs were absorbed with a median T(max) of 72 (range, 36-144) hours and eliminated with mean (%CV) t(½) of 92.7 (20.9%) and 87.4 (16.6%) hours, respectively. The GMRs (90% CIs) of the test to reference drug for C(max), AUC(0-t), and AUC(0-∞) were 0.99 (0.83-1.17), 0.95 (0.79-1.13), and 0.95 (0.80-1.13), respectively. Eleven of 21 (52.4%) and 8 of 21 (38.1%) subjects administered the test and reference drugs reported 22 and 21 AEs, respectively. Common AEs were headache (14.3%), throat irritation (8.5%), and epistaxis (9.5%). Three serious AEs related to a traffic accident (back, neck, and musculoskeletal pain) were reported in a test drug-treated subject. In this select group of Korean healthy male volunteers

  1. Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome: a SYSDIET sub-study.

    Science.gov (United States)

    Leder, Lena; Kolehmainen, Marjukka; Narverud, Ingunn; Dahlman, Ingrid; Myhrstad, Mari C W; de Mello, Vanessa D; Paananen, Jussi; Carlberg, Carsten; Schwab, Ursula; Herzig, Karl-Heinz; Cloetens, Lieselotte; Storm, Matilda Ulmius; Hukkanen, Janne; Savolainen, Markku J; Rosqvist, Fredrik; Hermansen, Kjeld; Dragsted, Lars O; Gunnarsdottir, Ingibjörg; Thorsdottir, Inga; Risérus, Ulf; Åkesson, Björn; Thoresen, Magne; Arner, Peter; Poutanen, Kaisa S; Uusitupa, Matti; Holven, Kirsten B; Ulven, Stine M

    2016-01-01

    Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study protocol. In this sub-study, we included subjects (n = 89) from three Nordic centers: Kuopio (n = 26), Lund (n = 30), and Oulu (n = 33) with a maximum weight change of ±4 kg, high-sensitivity C-reactive protein concentration ≤10 mg L(-1), and baseline body mass index expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. The healthy ND significantly down-regulated the expression of toll-like receptor 4 (TLR4), interleukin 18 (IL18), and thrombospondin receptor (CD36) mRNA transcripts and significantly up-regulated the expression of peroxisome proliferator-activated receptor delta (PPARD) mRNA transcript after the 2hOGTT compared to the CD. A healthy ND is able to modify the gene expression in PBMCs after a 2hOGTT. However, more studies are needed to clarify the biological and clinical relevance of these findings.

  2. Ultrasonographic contrast analysis between shoulder joint soft tissue inflammation and healthy shoulder peripheral soft tissue%肩关节软组织炎症与正常肩部周围软组织的声像图比较

    Institute of Scientific and Technical Information of China (English)

    赵亚平; 陈建权; 胡文江; 文莉

    2013-01-01

    Objective To comprehend the ultrasonic appearance of shouder joint soft tissue inflammation and healthy shoulder peripheral soft tissue,and to explore the value of high frequency ultrasound in diagnosing shoulder joint soft tissue inflammation .Methods High—frequency ultrasound was performed in 80 healthy adult, shoulders and 40 shoulders with soft tissue inflammation.Sonographic features of rotator cuff, muscular fasciae, shoulder burs a mucosa, joint capsule and other structures were evaluated.The differences between the two groups were compared.Results In case group,the main performance of various abnormal image in lesion area of shoulder joint consisted of increaseing, thickening and wide effusion area ,with tendon and tendon sheath echo—enhanced,edema,calcification and muscular fasciae rough,hyperplasia,echo disorder and so on.Compared with control group.affected tendon thickened obviously in case group ( P < 0.05).In lesion area of myofascitis.bursitis around shoulder and adhesive synovitis, myofascial thickness, bursal effusion depth and shoulder joint capsule wall thickness were significantly higher than the control group (P< 0.05).Conclusion Ultrasonography can display clearly the pathological changes of shoulder joint soft tissue inflammation , and their ultrasonic appearance have certain characteristic.%目的 比较肩关节软组织炎症患者和正常肩部周围软组织的声像图表现,探讨超声在诊断肩关节软组织炎症性病变中的价值.方法 对40例肩关节软组织炎症患者(病例组)肩袖、肌筋膜、肩滑膜囊及关节囊等部位进行超声检查,另选80正常成人(对照组)检测其相同部位,结果进行对比分析.结果 病例组肩部的各型异常图像以病变区受累部位测值的增大、增厚、积液区范围广泛等为主要表现,同时伴随肌腱、腱鞘回声增强,水肿、钙化,肌筋膜毛糙、增生、回声紊乱等多种异常声像.与正常对照组比较,病例组受

  3. Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance.

    Science.gov (United States)

    Jocken, Johan W E; Goossens, Gijs H; Boon, Hanneke; Mason, Rachael R; Essers, Yvonne; Havekes, Bas; Watt, Matthew J; van Loon, Luc J; Blaak, Ellen E

    2013-10-01

    Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men. Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7 ± 1 years), matched for age (58 ± 2 vs 62 ± 2 years), BMI (31.4 ± 0.6 vs 30.5 ± 0.6 kg/m(2)) and [Formula: see text] (28.9 ± 1.5 vs 29.5 ± 2.4 ml kg(-1) min(-1)) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic-euglycaemic clamp (8, 20 and 40 mU m(-2) min(-1)). AT and SM biopsies were collected to investigate underlying mechanisms. Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (-7 ± 6%, -13 ± 9% and -27 ± 9%) compared with men with NGT (-21 ± 7%, -38 ± 8% and -53 ± 8%) (p = 0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8 ± 3.1 vs 30.5 ± 2.0 μmol kg body weight(-1) min(-1); p lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. ClinicalTrials.gov NCT01680133.

  4. Immunohistological analysis of CD1a + langerhans cells and CD57 + natural killer cells in healthy and diseased human gingival tissue: A comparative study

    Directory of Open Access Journals (Sweden)

    Stelin Sahaya

    2009-01-01

    Full Text Available Background: Cell interaction between dendritic cells (DC and natural killer (NK cells in the periodontal milieu is not yet fully known, although these cells are individually known to contribute to the pathogenesis of periodontal disease. Materials and Methods: Fifty subjects (25 males and 25 females were included in the study. The subjects were divided into three groups: Group A comprised 16 subjects with clinically healthy gingiva; group B 17 subjects with gingivitis; and group C 17 subjects with gingivitis; and group C 17 subjects with moderate periodontitis (PPD ≥ 5 mm and CAL ≥ 3 mm in at least six sites. Gingival samples were collected and immunohistochemical study was done using CD57 and CD1a antibody. Statistical analysis was done using analysis of variance (ANOVA, followed by Tukey-Kramer multiple comparison for CD1a and Tukey′s highly significant difference (HSD test for CD57. Results and Conclusion: The study showed an inverse relationship between the CD1a+ (langerhans cells and CD57+ (natural killer cells. There was a significant increase in CD57+ cells and reduction in CD1a levels as periodontal disease progressed. The significant reduction in CD1a levels in periodontal disease when compared to health could possibly be a result of NK cells down regulating it. Reduction in CD1a levels may result in a low inflammatory response subsequently resulting in tissue destruction.

  5. Safety and tolerability of an intravenously administered alpha1-proteinase inhibitor at an increased infusion rate: a novel, randomized, placebo-masked, infusion rate-controlled, crossover study in healthy adults

    Directory of Open Access Journals (Sweden)

    Ngo LY

    2014-06-01

    Full Text Available Leock Y Ngo,1 Adam Haeberle,1 Jacqueline Dyck-Jones,1 David Gelmont,1 Leman Yel11Baxter Healthcare Corporation, Westlake Village, CA, USAPurpose: Alpha1-proteinase inhibitor (A1PI is indicated for chronic augmentation therapy in adults with emphysema due to congenital deficiency of A1PI. An intravenous infusion rate of 0.04 mL/kg/minute is currently recommended for the A1PI product, Glassia®. This randomized, placebo-masked, rate-controlled, crossover study was designed to evaluate the safety and tolerability of A1PI administration at an increased infusion rate.Patients and methods: A total of 30 healthy male and female subjects aged 19–61 years were enrolled. Each subject received simultaneous intravenous infusions of A1PI (Glassia® and placebo (human albumin 2.5% administered through a single infusion site on two separate treatment periods. Subjects were randomized in a 1:1 ratio to receive either test treatment (A1PI 0.2 mL/kg/minute + placebo 0.04 mL/kg/minute, or reference treatment (A1PI 0.04 mL/kg/minute + placebo 0.2 mL/kg/minute on Day 1. On Day 15, subjects received the other treatment regimen in a crossover sequence.Results: A total of 36 adverse events (AEs, regardless of causality, were reported; all were non-serious and of mild intensity, with headaches and dizziness occurring most frequently (12 [33.3%] and three [8.3%] of 36 AEs, respectively. Only seven AEs in six subjects were assessed as related to study treatment: with two AEs reported in two subjects treated with the 0.2 mL/kg/minute rate compared with five AEs in four subjects treated with the 0.04 mL/kg/minute rate.Conclusions: This study demonstrated the safety and tolerability of an A1PI product at an increased infusion rate (0.2 mL/kg/minute resulting in a shorter infusion duration in healthy subjects.Keywords: A1PI, Glassia, administration rate, Alpha-1 antitrypsin, ATT

  6. Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue

    Energy Technology Data Exchange (ETDEWEB)

    Schwab, Felix [Ludwig Maximilians-Univ. Hospital Munich (Germany). Inst. for Clinical Radiology; Schleede, Simone; Hahn, Dieter [Technische Univ. Muenchen, Garching (Germany). Dept. of Physics and Inst. of Medical Engineering] [and others

    2013-10-01

    Purpose: An experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. Materials and Methods: Lungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. Results: In all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p = 0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p = 0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p = 0.03). Conclusion: The contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI. (orig.)

  7. Tissue Doppler and speckle tracking strain echocardiography : from evaluation in healthy children to follow-up after surgery for a congenital heart defect

    NARCIS (Netherlands)

    Klitsie, Liselotte Maria

    2014-01-01

    This thesis provides insights in characteristics of newly introduced echocardiographic parameters in healthy children and their use in follow-up of patients with a congenital heart defect (CHD) after surgery. In healthy children, reference values and characteristics of two echocardiographic

  8. Healthy shiftwork, healthy shiftworks.

    Science.gov (United States)

    Kogi, K

    2001-12-01

    Reflecting diversifying shift systems, extensive effort is put into managing shiftwork and reducing safety and health risks. It is accepted that shiftworkers are exposed to particular risks inherent in their irregular work schedules. This raises the question of how and to what extent we can ensure healthy work life for shiftworkers. In answering the question, we need to identify effective measures to improve both shiftworking conditions and the health of shiftworkers. Based on recent experiences in managing shiftwork, we note three directions of such measures: (a) comprehensive action to avoid risk-enhancing conditions based on general guidelines, (b) risk control as to workload, worksite ergonomics and risk reduction, and (c) support for flexible and restful working life. International standards are obviously relevant to these three aspects. Our own experiences in applying a set of ergonomic checkpoints to plant maintenance shiftwork demonstrate the usefulness of focusing on flexible work schedules and on multiple job-related factors such as night workload, ergonomic environment, resting conditions and training. There is a strong need for participatory planning and implementation of multi-area improvements as well as for relying on flexible schedules and autonomic teamwork. We may conclude that healthy shiftwork and healthy shiftworkers are compatible with each other only when certain conditions are met. In achieving this end, we need to combine (a) comprehensive measures to improve work schedules and job life, (b) strict risk management and (c) locally adjusted participatory steps for continual improvement.

  9. Effects of dexamethasone, celecoxib, and methotrexate on the histology and metabolism of bone tissue in healthy Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Liu YZ

    2015-08-01

    Full Text Available Yanzhi Liu,1,2,* Yang Cui,3,* Yan Chen,1 Xiang Gao,4 Yanjie Su,1 Liao Cui1,2 1Department of Pharmacology, Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 3Department of Rheumatism Medicine, Guangdong General Hospital, Guangzhou, 4Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Objective: To investigate the long-term effects of three antiarthritics, namely dexamethasone, celecoxib, and methotrexate on the histology and metabolism of intact bone tissue in rats.Methods: Thirty-two 12-week-old healthy female Sprague Dawley rats were randomly allocated into four groups: 1 control (saline, daily; 2 dexamethasone (2 mg/kg, twice weekly; 3 celecoxib (50 mg/kg, daily; and 4 methotrexate (0.5 mg/kg, twice weekly. The drugs were administered to the rats for 12 weeks and the animals were weighed on a weekly basis. The femurs and lumbar vertebrae were harvested for bone mineral density and bone mechanical properties analyses. The proximal tibiae were processed for bone histomorphometry and micro-computed tomography analyses.Results: The following results were obtained: 1 dexamethasone strongly inhibited bone formation rate accompanied with a decrease in bone mineral density and bone biomechanical properties; 2 celecoxib stimulated bone resorption, leading to a decrease of bone mass and femur biomechanic properties; and 3 methotrexate caused bone loss and bone quality deterioration to a lesser extent due to the increase of the bone turnover rate on the proximal tibial metaphysis of the rats.Conclusion: This study provides a comparative profile of the long-term effects of clinical doses of celecoxib, methotrexate, and dexamethasone on intact skeletons of the rats

  10. CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph.

    Science.gov (United States)

    Carrega, Paolo; Bonaccorsi, Irene; Di Carlo, Emma; Morandi, Barbara; Paul, Petra; Rizzello, Valeria; Cipollone, Giuseppe; Navarra, Giuseppe; Mingari, Maria Cristina; Moretta, Lorenzo; Ferlazzo, Guido

    2014-04-15

    As limited information is available regarding the distribution and trafficking of NK cells among solid organs, we have analyzed a wide array of tissues derived from different human compartments. NK cells were widely distributed in most solid tissues, although their amount varied significantly depending on the tissue/organ analyzed. Interestingly, the distribution appeared to be subset specific, as some tissues were preferentially populated by CD56(bright)perforin(low) NK cells, with others by the CD56(dim)perforin(high) cytotoxic counterpart. Nevertheless, most tissues were highly enriched in CD56(bright)perforin(low) cells, and the distribution of NK subsets appeared in accordance with tissue gene expression of chemotactic factors, for which receptors are differently represented in the two subsets. Remarkably, chemokine expression pattern of tissues was modified after neoplastic transformation. As a result, although the total amount of NK cells infiltrating the tissues did not significantly change upon malignant transformation, the relative proportion of NK subsets infiltrating the tissues was different, with a trend toward a tumor-infiltrating NK population enriched in noncytotoxic cells. Besides solid tissues, CD56(bright)perforin(low) NK cells were also detected in seroma fluids, which represents an accrual of human afferent lymph, indicating that they may leave peripheral solid tissues and recirculate to secondary lymphoid organs via lymphatic vessels. Our results provide a comprehensive mapping of NK cells in human tissues, demonstrating that discrete NK subsets populate and recirculate through most human tissues and that organ-specific chemokine expression patterns might affect their distribution. In this context, chemokine switch upon neoplastic transformation might represent a novel mechanism of tumor immune escape.

  11. Immunogenicity and tolerability of inactivated flu vaccine In high risk and healthy children Inmunogenicidad y tolerancia de la vacuna inactivada anti-influenza en niños en alto riesgo y en controles sanos

    Directory of Open Access Journals (Sweden)

    Maria Luisa Avila Aguero

    2007-08-01

    Full Text Available We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe® in 154 children between 6 and 36 months of age at high risk of influenza- related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP. The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications.Se realizó un estudio clínico abierto para evaluar la inmunogenícidad y la seguridad de la vacuna inactivada anti-influenza, Imovax Gripe®, en 154 niños entre 6 y 36 meses de edad con alto riesgo de complicaciones ligadas a la influenza, y en un grupo de referencia de 64 niños sanos. El estudio fue

  12. Differentially expressed genes in adipocytokine signaling pathway of adipose tissue in pregnancy

    OpenAIRE

    Ogunyemi, Dotun; Xu, Jun; Mahesan, Arnold M.; Rad, Steve; Kim, Eric; Yano, Jacqueline; Alexander, Carolyn; Rotter, Jerome I.; Chen, Y.-D. Ida

    2013-01-01

    Objective To profile the differential gene expression of the KEGG Adipocytokine Signaling pathway in omental compared to subcutaneous tissue in normal pregnancy. Study Design Subjects included 14 nonobese, normal glucose tolerant, healthy pregnant women. Matched omental and subcutaneous tissue were obtained at elective cesarean delivery. Gene expression was evaluated using microarray and validated by RT-PCR. Differential gene expression was defined as ≥1.5 fold increase at p < 0.05. Results S...

  13. Hypoxyradiotherapy - changes in selected physiological parameters of healthy tissue during breathing of hypoxic gas-mixture; Hypoxie-Radiotherapie: Veraenderungen ausgewaehlter physiologischer Parameter des gesunden Gewebes bei Atmung eines hypoxischen Gasgemisches

    Energy Technology Data Exchange (ETDEWEB)

    Strnad, V. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Grebmeier, J. [Erlangen-Nuernberg Univ., Erlangen (Germany). Abt. Kernspintomographie; Riepl, M. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Kirschner, M. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie

    1994-10-01

    This study investigates changes in selected physiological parameters in vivo during acute aerogen hypoxia. In 31 persons (group A) we documented changes in blood-gas-analysis, ECG-parameters, blood pressure and pulse during acute hypoxia lasting 5 minutes. During 30 minutes of acute hypoxia we determined in another 10 persons (group B) in relations between different phosphoryl-metabolites by means of {sup 31}phosphorus magnetic resonance spectroscopy ({sup 31}P-MRS). The {sup 31}P-MRS of the Musculus triceps surae was performed on our 1,5 T imaging system (Magnetom, Siemens) using a 8 cm diameter surface coil. To achieve the hypoxic condition in the persons tested, a gas-mixture with 8.2% O{sub 2} was used. In group A the acute hypoxia led to significant changes in O{sub 2}-pressure, the blood O{sub 2}-saturation and pulse frequency. The pO{sub 2}-values drop in the 5th minute to about 50% of the inital value. Concerning group B the relations of the phosphoryl metabolities show no significant changes during acute hypoxia. The results show an excellent tolerability of breathing of the hypoxic gas-mixture, and confirm that this mixture containing 8.2% of O{sub 2} ensures a decrease in the pO{sub 2}-levels of more than 50%. This is necessary to achieve a dose modifying factor (DMF) of at least 1.15 to 1.2. The changes in relations of phosphoryl metabolites seem to reflect the ability of healthy tissue to adapt to hypoxic conditions starting after 10 minutes and leading to the loss of the radioprotective effect after 30 minutes. (orig.) [Deutsch] Die vorliegende Arbeit untersucht Veraenderungen ausgewaehlter physiologischer Parameter in vivo waehrend Hypoxie. Bei 31 Patienten (Gruppe A) habe wir waehrend akuter aerogener Hypoxie von fuenf Minuten Dauer Veraenderungen in der Blutgasanalyse, von EKG-Parametern, Blutdruck und Puls untersucht. Bei zehn Personen (Gruppe B) wurden waehrend akuter Hypoxie ueber 30 Minuten Veraenderungen der Phosphorylmetaboliten mit Hilfe der

  14. Evaluation of healthy muscle tissue by strain and shear wave elastography – Dependency on depth and ROI position in relation to underlying bone

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Carlsen, Jonathan Frederik; Christiansen, Iben Riishede

    2016-01-01

    and methods: Ten healthy volunteers (five males and five females) had their biceps brachii, gastrocnemius, and quadriceps muscle examined with strain- and shear wave elastography at three different depths and in regions located above bone and beside bone. Strain ratios were averaged from cine-loops of 10 s...

  15. Healthy Water

    Science.gov (United States)

    ... Topics Newsroom, Features, & Announcements CDC at Work: Healthy Water Fast Facts WASH-related Observances Top Causes of Drinking ... Features, & Announcements Training & Education CDC at Work: Healthy Water Policy & Recommendations Fast Facts Index of Water-Related Topics By A- ...

  16. Healthy Eating

    Science.gov (United States)

    ... Under Control Nutrition Guide for Toddlers Healthy Food Shopping What Should Preschoolers Drink? Healthy Drinks for Kids ... to Eating Right Learning About Calories Smart Supermarket Shopping Go, Slow, and Whoa! A Quick Guide to ...

  17. Healthy Schools

    Science.gov (United States)

    ... Wellness Policy Opportunities to create and support a healthy school environment. More Whole School, Whole Community, Whole Child A collaborative approach to learning and health Healthy Schools School Nutrition Environment Childhood Nutrition Facts Energy Drinks Obesity Prevention Youth ...

  18. Constitutive expression of a barley Fe phytosiderophore transporter increases alkaline soil tolerance and results in iron partitioning between vegetative and storage tissues under stress

    OpenAIRE

    Gómez-Galera, Sonia; Sudhakar, Duraialagaraja; Ana M. Pelacho; Capell, Teresa; Christou, Paul

    2012-01-01

    Cereals have evolved chelation systems to mobilize insoluble iron in the soil, but in rice this process is rather inefficient, making the crop highly susceptible to alkaline soils. We therefore engineered rice to express the barley iron-phytosiderophore transporter (HvYS1), which enables barley plants to take up iron from alkaline soils. A representative transgenic rice line was grown in standard (pH 5.5) or alkaline soil (pH 8.5) to evaluate alkaline tolerance and iron mobilizati...

  19. Clinical, microbiological, and immunological aspects of healthy versus peri-implantitis tissue in full arch reconstruction patients: a prospective cross-sectional study

    OpenAIRE

    Ata-Ali, Javier; Flichy-Fernández, Antonio Juan; Alegre-Domingo, Teresa; Ata-Ali, Fadi; Palacio, Jose; Peñarrocha-Diago, Miguel

    2015-01-01

    Background Due to the world-wide increase in treatments involving implant placement, the incidence of peri-implant disease is increasing. Late implant failure is the result of the inability to maintain osseointegration, whose most important cause is peri-implantitis. The aim of this study was to analyze the clinical, microbiological, and immunological aspects in the peri-implant sulcus fluid (PISF) of patients with healthy dental implants and patients with peri-implantitis. Methods PISF sampl...

  20. Expression of visfatin mRNA in adipose tissues of subjects with different glucose tolerance%内脂素基因在不同糖耐量个体脂肪组织的表达差异

    Institute of Scientific and Technical Information of China (English)

    姜秀云; 郑冬梅; 庄霞; 张海清; 孔磊; 管庆波; 赵家军

    2009-01-01

    Objective To investigate the difference of visfatin mRNA expression in abdominal subcutaneous and omental adipose tissues of type 2 diabetes and impaired glucose tolerance(the IGT group) and to explore the relationship between visfafin mRNA expression and indexes of correlation metabolism. Methods The subjects were Chinese Han population, including 23 controls with no family history of diabetes(the control group), 18 patients with impaired glucose tolerance(the IGT group) and 22 with type 2 diabetes(T2DM group). The blood pressure, FBG, TC, TG, HDL-C, LDL-C, HbA1c, and Fins were determined, and (T2DM BMI, WHR, and HOMA-IR were calculated. Semi-quantitative RT-PCR was used to determine visfatin mRNA expres-sion in adipose tissues. Results Visfatin mRNA expression of omental adipose tissues in the T2DM group was higher than that in the IGT and control groups(P0.05). There was no statistical difference in visfatin mRNA expression of subcutaneous adipose tissues among the three groups (P>0.05).Visfafin expression of omental adipose tissues in the fat/overweight group was higher than that in the control group (P0.05).对照组、IGT组及T2DM组皮下脂肪组织的内脂素基因表达量无统计学差异(P>0.05).肥胖/超重组网膜脂肪组织的内脂素基因表达量高于体质量正常组(P0.05),而皮下脂肪组织内脂素基因表达则与,TC相关(P<0.05).结论内脂素在汉族人群T2DM、肥胖者中表达增加,且主要在内脏脂肪组织中表达,在维持葡萄糖稳态平衡中发挥作用.

  1. Om tolerance

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2007-01-01

    Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik.......Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik....

  2. Om tolerance

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2007-01-01

    Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik.......Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik....

  3. Lack of tissue accumulation of grape seed flavanols after daily long-term administration in healthy and cafeteria-diet obese rats.

    Science.gov (United States)

    Margalef, Maria; Pons, Zara; Iglesias-Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

    2015-11-18

    After ingestion flavanols are metabolized by phase-II enzymes and the microbiota and are distributed throughout the body depending on several factors. Herein we aim to evaluate whether flavanols are tissue-accumulated after the long-term administration of a grape seed polyphenol extract (GSPE) in rats and to study if compounds present in tissues differ in a cafeteria-diet obesity state. For that, plasma, liver, mesenteric white adipose tissue (MWAT), brain, and aorta flavanol metabolites from standard chow-diet-fed (ST) and cafeteria-diet-fed (CAF) rats were analyzed by high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) 21 h after the last 12-week-daily GSPE (100 mg/kg) dosage. Results showed that long-term GSPE intake did not trigger a flavanol tissue accumulation, indicating a clearance of products at each daily dosage. Therefore, results suggest that polyphenol benefits in a disease state would be due to a daily pulsatile effect. Moreover, obesity induced by diet also influences the metabolism and bioavailability of flavanols in rats.

  4. Expression stability of reference genes for quantitative RT-PCR of healthy and diseased pituitary tissue samples varies between humans, mice, and dogs

    NARCIS (Netherlands)

    van Rijn, Sarah J; Riemers, Frank M; van den Heuvel, Douwe; Wolfswinkel, Jeannette; Hofland, Leo; Meij, Björn P; Penning, Louis C

    2014-01-01

    Pituitary surgery generates pituitary tissue for histology, immunohistochemistry, and molecular biological research. In the last decade, the pathogenesis of pituitary adenomas has been extensively studied in humans, and to a lesser degree in dogs, and tumor oncogenesis has been studied in knock-out

  5. Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome

    DEFF Research Database (Denmark)

    Kolehmainen, Marjukka; Ulven, Stine M; Paananen, Jussi

    2015-01-01

    in gene expression are associated with clinical and biochemical effects. DESIGN: Obese adults with features of the metabolic syndrome underwent an 18- to 24-wk randomized intervention study comparing the ND with the control diet (CD) (the SYSDIET study, carried out within Nordic Centre of Excellence...... sites for the nuclear transcription factor κB. CONCLUSION: A healthy Nordic diet reduces inflammatory gene expression in SAT compared with a control diet independently of body weight change in individuals with features of the metabolic syndrome. The study was registered at clinicaltrials.gov as NCT...

  6. [Tolerance and safety of drug arglabin].

    Science.gov (United States)

    Tabriz, N S; Skak, K S; Mytaikhan, Zh M; Kozhamuratov, M T; Serikbaev, N M

    2014-12-01

    The clinical researches were carried out on tolerance and safety of using an original medical drug Arglabin in capsules as immunomodulator. By results of researches the drug showed good tolerance and safety in healthy volunteers. Drug Arglabin in capsules as immunomodulator can be recommend for the further studying in the clinical practice.

  7. Desiccation tolerance of somatic embryoids.

    OpenAIRE

    Tetteroo, F.A.A.

    1996-01-01

    This thesis describes the research performed on the subject "Desiccation tolerance in somatic embryoids". Somatic embryoids are bipolar structures formed in tissue culture, with both a shoot and a root apex, which resemble very much zygotic embryos found in seeds. Through simultaneous development of root and shoot, these embryoids can grow out into complete plantlets.In Chapter 2 we describe an optimized method to produce completely desiccation tolerant carrot ( Daucus carota ) embryoids. Usi...

  8. Towards Tolerance

    NARCIS (Netherlands)

    Lisette Kuyper; Jurjen Iedema; Saskia Keuzenkamp

    2013-01-01

    Across Europe, public attitudes towards lesbian, gay and bisexual (LGB) individuals range from broad tolerance to widespread rejection. Attitudes towards homosexuality are more than mere individual opinions, but form part of the social and political structures which foster or hinder the equality

  9. Repressive Tolerance

    DEFF Research Database (Denmark)

    Pedersen, Morten Jarlbæk

    2016-01-01

    to an administrative culture of repressive tolerance of organised interests: authorities listen but only reacts in a very limited sense. This bears in it the risk of jeopardising the knowledge transfer from societal actors to administrative ditto thus harming the consultation institutions’ potential for strengthening...

  10. Healthy Eyes

    Science.gov (United States)

    ... los Ojos Cómo hablarle a su oculista Healthy Eyes Having a comprehensive dilated eye exam is one ... or contact lenses. What is a comprehensive dilated eye exam? A comprehensive dilated eye exam is a ...

  11. Healthy Ageing

    NARCIS (Netherlands)

    Dr. C.P. van der Schans

    2015-01-01

    Presentatie gehouden bij de bijeenkomst voor het Regionaal Genootschap Fysiotherapie Het Noorden op 10 februari te Marum, over het belang van fysieke activiteit voor healthy ageing en de rol van de fysiotherapeut hierin

  12. Healthy Places

    Centers for Disease Control (CDC) Podcasts

    2007-04-10

    Every person has a stake in environmental public health. As the environment deteriorates, so does the physical and mental health of the people within it. Healthy places are those designed and built to improve the quality of life for all people who live, work, worship, learn, and play within their borders -- where every person is free to make choices amid a variety of healthy, available, accessible, and affordable options. The CDC recognizes significant health issues and places that are vital in developing the Healthy Places program and provides examples in this report.  Created: 4/10/2007 by CDC National Center for Environmental Health.   Date Released: 4/13/2007.

  13. {sup 68}Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kroiss, A.; Putzer, D.; Decristoforo, C.; Uprimny, C.; Warwitz, B.; Nilica, B.; Gabriel, M.; Kendler, D.; Waitz, D.; Virgolini, I.J. [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Widmann, G. [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-04-15

    We wanted to establish the range of {sup 68}Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 {sup 68}Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUV{sub max} (mean {+-} standard deviation) values of {sup 68}Ga-DOTA-TOC were 29.8 {+-} 16.5 in 162 liver metastases, 19.8 {+-} 18.8 in 89 bone metastases and 34.6 {+-} 17.1 in 43 pancreatic NET (33.6 {+-} 14.3 in 30 tumours of the uncinate process and 36.3 {+-} 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV{sub max} (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV{sub max} between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV{sub max} for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001). {sup 68}Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV{sub max} can offer important clinical

  14. Desiccation tolerance of somatic embryoids.

    NARCIS (Netherlands)

    Tetteroo, F.A.A.

    1996-01-01

    This thesis describes the research performed on the subject "Desiccation tolerance in somatic embryoids". Somatic embryoids are bipolar structures formed in tissue culture, with both a shoot and a root apex, which resemble very much zygotic embryos found in seeds. Through simultaneous development of

  15. Healthy Learning.

    Science.gov (United States)

    Kennedy, Mike

    2003-01-01

    Offers ten suggestions for schools and universities to help maintain a healthy indoor environment: proper flooring, sanitary washrooms, consistent maintenance, indoor air quality, preventing mold, daylighting, good acoustics, avoiding volatile organic compounds (VOCs), ergonomic furniture, and well-maintained roofs. (EV)

  16. Healthy Dragon

    Institute of Scientific and Technical Information of China (English)

    孙继山

    2005-01-01

    The Chinese economic dragon is healthy and dynamic. The dragorthead,Shanghai, is developing at a pace never before seen in world history, The dragon's body is also doing well, not least because there is tremendous competition across the country. Thus, four cities along the central Yangtze River Region are trying to strengthen their competitiveness.

  17. Studies on 4 Tomato Varieties Tolerance to NaCl Stress under Tissue Culture Condition%组织培养条件下番茄4个品种对NaCl胁迫耐受性的研究

    Institute of Scientific and Technical Information of China (English)

    王萍; 孟哓琴; 钟影; 王罡; 季静

    2013-01-01

    Using hypocotyls of tomato (Lycopersicon esculentum Mill.)varieties‘Baiguo-qiangfeng’,‘Hongniuxin’,‘Xiaohongxiantao’ and ‘Hongshengnv’ as explants,we added 0 mmol·L-1,50 mmol·L-1,100 mmol·L-1,150 mmol·L-1 and 200 mmol·L-1 NaCl in the media, and investigated the changes in induction rates of callus formation and adventitious bud under the stress of different NaCl levels.We also evaluated tolerance of 4 tomato varieties to NaCl stress under the condition of tissue culture.At the same time,we probed into the effects of chlorine fumigation time on tomato seed’s growth and germination,when it was used in tomato seed disinfection. The results showed that 7 h chlorine fumigation for tomato seeds had the best effect. The capacity of hypocotyls tissue culture of 4 tomato varieties and their tolerance to NaCl were different.The induction rates of callus formation and adventitious bud of ‘Baiguoqiangfeng’ and ‘Hongshengnv’ were relatively high.100 mmol·L-1 and 50 mmol·L-1 NaCl were suitable for ‘Baiguoqiangfeng’ and ‘Hongshengnv’,respectively when NaCl was applied as selective agent to screen transformants.%  以番茄品种白果强丰、红牛心、小红仙桃、红圣女的下胚轴为外植体,在培养基中分别添加0、50、100、150 mmol·L-1和200 mmol·L-1 NaCl,研究在不同浓度NaCl胁迫下番茄愈伤组织诱导率与不定芽诱导率的变化,评价4个品种番茄在组织培养条件下对NaCl胁迫的耐受性。同时探讨氯气熏蒸法用于番茄种子消毒时,熏蒸时间对番茄种子萌发与生长的影响。结果表明:氯气熏蒸番茄种子7 h的消毒效果最好。4个品种番茄的下胚轴组织培养能力和对NaCl的耐受性均表现不同,白果强丰和红圣女的愈伤组织诱导率和不定芽诱导率较高;当以NaCl作为抗性筛选剂对转化后代进行筛选时,适宜筛选浓度白果强丰为100 mmol·L-1、红圣女为50 mmol·L-1。

  18. Flooding tolerance of forage legumes.

    Science.gov (United States)

    Striker, Gustavo G; Colmer, Timothy D

    2016-06-20

    We review waterlogging and submergence tolerances of forage (pasture) legumes. Growth reductions from waterlogging in perennial species ranged from >50% for Medicago sativa and Trifolium pratense to Lotus corniculatus, L. tenuis, and T. fragiferum For annual species, waterlogging reduced Medicago truncatula by ~50%, whereas Melilotus siculus and T. michelianum were not reduced. Tolerant species have higher root porosity (gas-filled volume in tissues) owing to aerenchyma formation. Plant dry mass (waterlogged relative to control) had a positive (hyperbolic) relationship to root porosity across eight species. Metabolism in hypoxic roots was influenced by internal aeration. Sugars accumulate in M. sativa due to growth inhibition from limited respiration and low energy in roots of low porosity (i.e. 4.5%). In contrast, L. corniculatus, with higher root porosity (i.e. 17.2%) and O2 supply allowing respiration, maintained growth better and sugars did not accumulate. Tolerant legumes form nodules, and internal O2 diffusion along roots can sustain metabolism, including N2 fixation, in submerged nodules. Shoot physiology depends on species tolerance. In M. sativa, photosynthesis soon declines and in the longer term (>10 d) leaves suffer chlorophyll degradation, damage, and N, P, and K deficiencies. In tolerant L corniculatus and L. tenuis, photosynthesis is maintained longer, shoot N is less affected, and shoot P can even increase during waterlogging. Species also differ in tolerance of partial and complete shoot submergence. Gaps in knowledge include anoxia tolerance of roots, N2 fixation during field waterlogging, and identification of traits conferring the ability to recover after water subsides.

  19. Healthy Water Healthy People Field Monitoring Guide

    Science.gov (United States)

    Project WET Foundation, 2003

    2003-01-01

    This 100-page manual serves as a technical reference for the "Healthy Water, Healthy People Water Quality Educators Guide" and the "Healthy Water Healthy People Testing Kits". Yielding in-depth information about ten water quality parameters, it answers questions about water quality testing using technical overviews, data interpretation guidelines,…

  20. Interaction between insulin (VNTR) and hepatic lipase (LIPC-514C>T) variants on the response to an oral glucose tolerance test in the EARSII group of young healthy men.

    Science.gov (United States)

    Waterworth, Dawn M; Jansen, Hans; Nicaud, Viviane; Humphries, Steve E; Talmud, Philippa J

    2005-06-10

    Insulin resistance is polygenic in origin, and can be observed at an early age. We have shown that variations in APOC3-482T>C and hepatic lipase (LIPC)-514C>T), individually (APOC3 alone) and interactively, modulate insulin and glucose levels after an OGTT in young healthy men participating in the European Atherosclerosis Research Study II (EARSII). Variation in the insulin gene (INS) variable number tandem repeat (VNTR) has been found to predispose to type 1 and type 2 diabetes. We have evaluated the HphI site 23 bp upstream of the INS gene (a surrogate marker for the VNTR) in EARSII (n=822), to determine if variation in INS contributes to insulin resistance. Carriers of the INS VNTR class III (HphI-) allele (frequency=0.29 (95%CI 0.27, 0.31)) had significantly higher 60-min insulin concentrations after the OGTT (P=0.014) and a marginally higher AUC insulin (P=0.07), compared to class I (HphI+) homozygotes. However, this effect on AUC insulin was modified by the level of physical activity, displaying significant gene:environment interaction (P=0.03). We tested for gene:gene interaction between the INS VNTR and both the LIPC-514C>T and APOC3-482T>C. While there was a significant interaction between INS VNTR and LIPC-514C>T on AUC glucose (P=0.013) and on AUC insulin (P=0.015), there was no interaction with APOC3-482T>C. Thus, despite a modest effect of the INS VNTR alone, the influence of this variant on insulin sensitivity was modified by gene:environment and gene:gene interactions, illustrating the biological complexity of insulin resistance.

  1. Bellagio report on Healthy agriculture, healthy nutrition, healthy people⋆

    OpenAIRE

    Simopoulos Artemis P.; Bourne Peter G.; Faergeman Ole

    2013-01-01

    The Bellagio Report on Healthy agriculture, healthy nutrition, healthy people is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that m...

  2. Toleration, Groups, and Multiculturalism

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    to the political and social relationship between the subject and the objects of toleration. Finally, toleration is often argued to be a normative requirement on the basis of the way it affects the object or receiver of toleration, e.g. on the basis of the good of or right to freedom from non-interference which......The chapter considers how groups might be relevant as objects of policies of toleration and the different senses 'group' might have in relation to questions of toleration. The chapter argues that groups can be relevant to toleration in several different ways as objects of toleration. Toleration...... is routinely defined as involving an objection component, a power requirement and an acceptance component. The objection and acceptance components refer to reasons or dispositions of the subjects of toleration, e.g. public authorities deciding how to act in relation to groups. The power condition refers...

  3. Influencing factors of growth hormone in response to insulin tolerance test in 50 healthy adults%50名健康成人生长激素对胰岛素耐量试验反应性的影响因素

    Institute of Scientific and Technical Information of China (English)

    宋向欣; 顾锋; 徐焱成; 葛家璞; 崔立全

    2014-01-01

    胰岛素耐量试验(ITT)激发的生长激素(GH)峰值是诊断成人生长激素缺乏症的“金标准”.本研究探讨50名中国健康成人中ITT激发的GH峰值的受影响因素.结果显示血糖谷值或血糖下降幅度与GH峰值无相关性.在多元回归分析中,ITT激发的GH与体重指数呈负相关(P<0.01),与年龄、性别和腹围无显著相关性.%The peak level of growth hormone (GH) stimulated by insulin tolerance test (ITT) is the " gold standard" for diagnosis of growth hormone deficiency in adults.This study was aimed to explore the factors influencing GH response to ITT in 50 healthy adults.The results showed that the nadir or decreased amplitude of blood glucose was not related to GH peak level.In multivariable analysis,the GH level stimulated by ITT was negatively associated with body mass index(P<0.01),but there was no any association with age,gender,and waist circumference.

  4. Lactose tolerance tests

    Science.gov (United States)

    Hydrogen breath test for lactose tolerance ... Two common methods include: Lactose tolerance blood test Hydrogen breath test The hydrogen breath test is the preferred method. It measures the amount of hydrogen ...

  5. Healthy Vision Tips

    Science.gov (United States)

    ... NEI for Kids > Healthy Vision Tips All About Vision About the Eye Ask a Scientist Video Series ... Links to More Information Optical Illusions Printables Healthy Vision Tips Healthy vision starts with you! Use these ...

  6. Healthy Lifestyle: Children's Health

    Science.gov (United States)

    Healthy Lifestyle Children's health You want your child to eat healthy foods, but do you know which nutrients ... 16, 2016 Original article: http://www.mayoclinic.org/healthy-lifestyle/childrens-health/in-depth/nutrition-for-kids/art- ...

  7. Keeping Your Voice Healthy

    Science.gov (United States)

    ... Find an ENT Doctor Near You Keeping Your Voice Healthy Keeping Your Voice Healthy Patient Health Information ... heavily voice-related. Key Steps for Keeping Your Voice Healthy Drink plenty of water. Moisture is good ...

  8. Healthy food trends -- kale

    Science.gov (United States)

    Healthy food trends - borecole; Healthy snacks - kale; Weight loss - kale; Healthy diet - kale; Wellness - kale ... drugs), you may need to limit vitamin K foods. Vitamin K can affect how these medicines work. ...

  9. Having a Healthy Pregnancy

    Science.gov (United States)

    ... Week of Healthy Breakfasts Shyness Having a Healthy Pregnancy KidsHealth > For Teens > Having a Healthy Pregnancy A ... or she can help you to get treatment. Pregnancy Discomforts Pregnancy can cause some uncomfortable side effects. ...

  10. Healthy Dining Hall Eating

    Science.gov (United States)

    ... A Week of Healthy Breakfasts Shyness Healthy Dining Hall Eating KidsHealth > For Teens > Healthy Dining Hall Eating ... likely to eat. previous continue Overcoming Common Dining Hall Mistakes Even the most attentive diners can still ...

  11. Healthy Sleep Habits

    Science.gov (United States)

    ... Sleep Apnea Testing CPAP Healthy Sleep Habits Healthy Sleep Habits Your behaviors during the day, and especially ... team at an AASM accredited sleep center . Quick Sleep Tips Follow these tips to establish healthy sleep ...

  12. Healthy food trends -- quinoa

    Science.gov (United States)

    Healthy food trends - goosefoot; Healthy snacks - quinoa; Weight loss - quinoa; Healthy diet - quinoa; Wellness - quinoa ... Quinoa is rich in protein . It has almost twice the amount of protein found in oats, and ...

  13. Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People

    OpenAIRE

    Ole Faergeman; Simopoulos, Artemis P.; Peter G. Bourne

    2013-01-01

    The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD’s) wo...

  14. Fault Tolerant Feedback Control

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Niemann, H.

    2001-01-01

    An architecture for fault tolerant feedback controllers based on the Youla parameterization is suggested. It is shown that the Youla parameterization will give a residual vector directly in connection with the fault diagnosis part of the fault tolerant feedback controller. It turns out...... that there is a separation be-tween the feedback controller and the fault tolerant part. The closed loop feedback properties are handled by the nominal feedback controller and the fault tolerant part is handled by the design of the Youla parameter. The design of the fault tolerant part will not affect the design...... of the nominal feedback con-troller....

  15. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2004-01-01

    BackgroundDimensioning and TolerancingTolerance Format and Decimal PlacesConverting Plus/Minus Dimensions and Tolerances into Equal Bilaterally Toleranced DimensionsVariation and Sources of VariationTolerance AnalysisWorst-case Tolerance StackupsStatistical Tolerance StackupsGeometric Dimensioning and Tolerancing (GD&T)Converting Plus/Minus Tolerancing to Positional Tolerancing and Projected Tolerance ZonesDiametral and Radial Tolerance StackupsSpecifying Material Condition Modifiers and Their Effect on Tolerance Stackups The Tolerance Stackup SketchThe Tolerance Stackup Report FormTolerance S

  16. Compromise and Toleration

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature......, justification, and limits of compromise if we see it merely as a matter of toleration. While toleration is mainly a matter of accepting citizens' equal right to co-existence as subjects to law, political compromise includes the parties in making law – it makes them co-authors of law. Toleration entails...... respecting the plurality of conceptions of the good in society, whereas political compromise embodies the disagreements in coercive laws. This difference between toleration and compromise has two important consequences. First, political compromise is justified in a different manner than is toleration...

  17. Immune mechanisms in cerebral ischemic tolerance

    Directory of Open Access Journals (Sweden)

    Lidia eGarcia-Bonilla

    2014-03-01

    Full Text Available Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance. These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral ischemic tolerance acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish ischemic tolerance and that ischemic tolerance can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of ischemic tolerance and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies.

  18. Advances in tissue engineering

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Tissue engineering is a newly developed specialty involved in the construction of tissues and organs either in vitro or in vivo. Tremendous progress has been achieved over the past decade in tisse construction as well as in other related areas, such as bone marrow stromal cells, embryonic stem cells and tissue progenitor cells. In our laboratory, tissues of full-thickness skin, bone, cartilage and tendon have been successfully engineered, and the engineered tissues have repaired full-thickness skin wound, cranial bone defects, articular cartilage defects and tendon defects in animals. In basic research areas, bone marrow stromal cells have been induced and transformed into osteoblasts and chondrocytes in vitro. Mouse embryo stem cell lines we established have differentiated into neuron precursor, cardiac muscle cells and epithelial cells. Genetic modifications of seed cells for promoting cell proliferation, delaying cell aging and inducing immune tolerance have also been investigated.

  19. Offspring's Tolerance of Mother Goes Viral.

    Science.gov (United States)

    Kinder, Jeremy M; Jiang, Tony T; Way, Sing Sing

    2016-05-17

    Pregnancy uniquely allows genetically discordant tissues of the mother and child to intimately coexist in harmony. In this issue of Immunity, Ou and colleagues show that hepatitis B virus exploits these naturally occurring immune tolerance pathways to establish persistent postnatal infection in offspring.

  20. Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA

    Science.gov (United States)

    Richie, Thomas L.; Charoenvit, Yupin; Wang, Ruobing; Epstein, Judith E.; Hedstrom, Richard C.; Kumar, Sanjai; Luke, Thomas C.; Freilich, Daniel A.; Aguiar, Joao C.; Sacci, Jr., John B.; Sedegah, Martha; Nosek, Jr., Ronald A.; De La Vega, Patricia; Berzins, Mara P.; Majam, Victoria F.; Abot, Esteban N.; Ganeshan, Harini; Richie, Nancy O.; Banania, Jo Glenna; Baraceros, Maria Fe B.; Geter, Tanya G.; Mere, Robin; Bebris, Lolita; Limbach, Keith; Hickey, Bradley W.; Lanar, David E.; Ng, Jennifer; Shi, Meng; Hobart, Peter M.; Norman, Jon A.; Soisson, Lorraine A.; Hollingdale, Michael R.; Rogers, William O.; Doolan, Denise L.; Hoffman, Stephen L.

    2012-01-01

    When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997−1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000–2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines. PMID:23151451

  1. System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

    Science.gov (United States)

    Kologrivova, I V; Suslova, T E; Koshel'skaya, O A; Vinnitskaya, I V; Trubacheva, O A

    2014-03-01

    The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

  2. Stem cells and healthy aging.

    Science.gov (United States)

    Goodell, Margaret A; Rando, Thomas A

    2015-12-04

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.

  3. Tolerance of the carotid-sheath contents to brachytherapy: an experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Werber, J.L.; Sood, B.; Alfieri, A.; McCormick, S.A.; Vikram, B. (Department of Otolaryngology--Head and Neck Surgery, New York Medical College, Beth Israel (USA))

    1991-06-01

    Tumor invasion of the carotid artery is a potential indication for brachytherapy, which delivers a high dose of irradiation to residual tumor while limiting the dose to adjacent healthy tissues. The tolerance of carotid-sheath contents to varying doses of brachytherapy, however, has not been clearly established. In order to evaluate brachytherapy effects on carotid-sheath contents, after-loading catheters were implanted bilaterally in 3 groups of 6 rabbits each (18 rabbits). Iridium 192 brachytherapy doses of either 5000 cGy (rad), 9000 cGy, or 13,000 cGy were delivered unilaterally, with the contralateral neck serving as a nonirradiated control in each animal. There were no carotid ruptures and wound healing was normal. Two animals from each group were killed at 6, 20, and 48 weeks. Even at the highest dose (13,000 cGy), nerve conduction studies performed on the vagus nerve prior to sacrifice revealed no increased latency, histologic changes were minimal, and carotid arteries were patent. These observations suggest that the carotid-sheath contents in healthy rabbits could tolerate high doses (up to 13,000 cGy) of low-dose-rate interstitial brachytherapy without complications.

  4. MERICAN CULTURAL TOLERANCE

    Institute of Scientific and Technical Information of China (English)

    ZHANG RUIXIAO

    2014-01-01

    As an emigrant country, the essential characteristic of America culture is its tolerance. It contributes to the formation the diversity of American culture. By tracing back to American history, this essay shows what caused American cultural tolerance. Through describing briefly the manifestation of American cultural tolerance from certain aspects and analyzing the major factors, it will give us a clue about the reason why America can be always prosperous. At last, the paper shows the limitation as well as advantages about the tolerance from the point of current status.

  5. Healthy Modern Landscape Inherited from Hakka Culture

    Directory of Open Access Journals (Sweden)

    Huang Hui

    2016-01-01

    Full Text Available The Hakka modern landscape is guided by its spirit of ambition, optimism, tolerance, and enterprising. The Meizhou Ruishan Agricultural and Ecological Garden Project (phase 1 combines the attributes of colors, materials and forms from the traditional Hakka architecture, Hakka culture, and the healthy landscape as a general concept and study. Thus, a new concept of modern Hakka landscape has been put forward through practice.

  6. Does Metabolically Healthy Obesity Exist?

    Science.gov (United States)

    Muñoz-Garach, Araceli; Cornejo-Pareja, Isabel; Tinahones, Francisco J.

    2016-01-01

    The relationship between obesity and other metabolic diseases have been deeply studied. However, there are clinical inconsistencies, exceptions to the paradigm of “more fat means more metabolic disease”, and the subjects in this condition are referred to as metabolically healthy obese (MHO).They have long-standing obesity and morbid obesity but can be considered healthy despite their high degree of obesity. We describe the variable definitions of MHO, the underlying mechanisms that can explain the existence of this phenotype caused by greater adipose tissue inflammation or the different capacity for adipose tissue expansion and functionality apart from other unknown mechanisms. We analyze whether these subjects improve after an intervention (traditional lifestyle recommendations or bariatric surgery) or if they stay healthy as the years pass. MHO is common among the obese population and constitutes a unique subset of characteristics that reduce metabolic and cardiovascular risk factors despite the presence of excessive fat mass. The protective factors that grant a healthier profile to individuals with MHO are being elucidated. PMID:27258304

  7. Fault tolerant computing systems

    CERN Document Server

    Randell, B

    1981-01-01

    Fault tolerance involves the provision of strategies for error detection, damage assessment, fault treatment and error recovery. A survey is given of the different sorts of strategies used in highly reliable computing systems, together with an outline of recent research on the problems of providing fault tolerance in parallel and distributed computing systems. (15 refs).

  8. Tolerances in micro manufacturing

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Zhang, Yang; Islam, Aminul

    2017-01-01

    This paper describes a method for analysis of tolerances in micro manufacturing. It proposes a mapping oftolerances to dimensions and compares this with current available international standards. The analysisdocuments that tolerances are not scaled down as the absolute dimension. In practice...

  9. Loss Tolerant Optical Qubits

    CERN Document Server

    Ralph, T C; Gilchrist, A; Gilchrist, Alexei

    2005-01-01

    We present a linear optics quantum computation scheme that employs a new encoding approach that incrementally adds qubits and is tolerant to photon loss errors. The scheme employs a circuit model but uses techniques from cluster state computation and achieves comparable resource usage. To illustrate our techniques we describe a quantum memory which is fault tolerant to photon loss.

  10. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...

  11. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    Under conditions of pluralism different cultures, interests or values can come into conflict, which raises the problem of how to secure peaceful co-existence. The idea of toleration historically emerged as an answer to this problem. Recently Rainer Forst has argued that toleration should not just...

  12. A Lesson in Tolerance

    Science.gov (United States)

    Johnt, Marlene

    2004-01-01

    This article describes one classroom's experience integrating a three-part lesson that focused on tolerance. In the lesson, students examined works by American folk-art painter Edward Hicks, researched quotes about tolerance in society, and applied calligraphy skills to an original composition.

  13. Remember Tolerance Differently

    DEFF Research Database (Denmark)

    Tønder, Lars

    2012-01-01

    This essay questions the linear conception of history which often accompanies the way contemporary democratic theory tends to disavow tolerance's discontinuities and remainders. In the spirit of Foucault's genealogy of descent, the idea is to develop a new sense of tolerance's history, not by inv...

  14. Activation of natural killer T Cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signalling axis in obesity

    NARCIS (Netherlands)

    Ji, Y.; Sun, S.; Xu, Aimin; Bhargava, P.; Yang, Liu; Lam, K.S.L.; Gao, Bin; Lee, Chih-Hao; Kersten, A.H.; Qi, L.

    2012-01-01

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type

  15. Activation of natural killer T Cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signalling axis in obesity

    NARCIS (Netherlands)

    Ji, Y.; Sun, S.; Xu, Aimin; Bhargava, P.; Yang, Liu; Lam, K.S.L.; Gao, Bin; Lee, Chih-Hao; Kersten, A.H.; Qi, L.

    2012-01-01

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type

  16. Microglial activation in healthy aging.

    Science.gov (United States)

    Schuitemaker, Alie; van der Doef, Thalia F; Boellaard, Ronald; van der Flier, Wiesje M; Yaqub, Maqsood; Windhorst, Albert D; Barkhof, Frederik; Jonker, Cees; Kloet, Reina W; Lammertsma, Adriaan A; Scheltens, Philip; van Berckel, Bart N M

    2012-06-01

    Healthy brain aging is characterized by neuronal loss and decline of cognitive function. Neuronal loss is closely associated with microglial activation and postmortem studies have indeed suggested that activated microglia may be present in the aging brain. Microglial activation can be quantified in vivo using (R)-[(11)C]PK11195 and positron emission tomography. The purpose of this study was to measure specific binding of (R)-[(11)C]PK11195 in healthy subjects over a wide age range. Thirty-five healthy subjects (age range 19-79 years) were included. In all subjects 60-minute dynamic (R)-[(11)C]PK11195 scans were acquired. Specific binding of (R)-[(11)C]PK11195 was calculated using receptor parametric mapping in combination with supervised cluster analysis to extract the reference tissue input function. Increased binding of (R)-[(11)C]PK11195 with aging was found in frontal lobe, anterior and posterior cingulate cortex, medial inferior temporal lobe, insula, hippocampus, entorhinal cortex, thalamus, parietal and occipital lobes, and cerebellum. This indicates that activated microglia appear in several cortical and subcortical areas during healthy aging, suggesting widespread neuronal loss.

  17. [Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People].

    Science.gov (United States)

    Simopoulos, Artemis P; Bourne, Peter G; Faergeman, Ole

    2013-11-01

    The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October-2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD's) worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  18. Bellagio report on healthy agriculture, healthy nutrition, healthy people.

    Science.gov (United States)

    Simopoulos, Artemis P; Bourne, Peter G; Faergeman, Ole

    2013-02-05

    The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October-2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD's) worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  19. Bellagio report on Healthy agriculture, healthy nutrition, healthy people⋆

    Directory of Open Access Journals (Sweden)

    Simopoulos Artemis P.

    2013-07-01

    Full Text Available The Bellagio Report on Healthy agriculture, healthy nutrition, healthy people is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD’s worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  20. Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People

    Directory of Open Access Journals (Sweden)

    Ole Faergeman

    2013-02-01

    Full Text Available The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD’s worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  1. Expect Respect: Healthy Relationships

    Science.gov (United States)

    ... Pediatrician Ages & Stages Prenatal Baby Toddler Preschool Gradeschool Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Abuse Young Adult Healthy Children > Ages & Stages > Teen > Dating & Sex > Expect Respect: Healthy Relationships Ages & Stages Listen Español ...

  2. Healthy Environments for Children

    Science.gov (United States)

    ... OUTSIDE, THEY NEED CARE AND AFFECTION IN A HEALTHY ENVIRONMENT! ...AT SCHOOL... 2 ...AT HOME... ...EVEN IN THEIR ... CAN WE DO? HOW CAN WE GUARANTEE A HEALTHY FUTURE FOR ... PROTECTING THE ENVIRONMENT, ESPECIALLY RIVERS AND FORESTS, WE CAN IMPROVE THE ...

  3. tolerance: An R Package for Estimating Tolerance Intervals

    OpenAIRE

    Derek S. Young

    2010-01-01

    The tolerance package for R provides a set of functions for estimating and plotting tolerance limits. This package provides a wide-range of functions for estimating discrete and continuous tolerance intervals as well as for estimating regression tolerance intervals. An additional tool of the tolerance package is the plotting capability for the univariate and regression settings as well as for the multivariate normal setting. The tolerance package's capabilities are illustrated using simulated...

  4. Thalassemia: Healthy Living

    Science.gov (United States)

    ... Thalassemia” More What can a person living with thalassemia do to stay healthy? A healthy lifestyle is ... disorder”, as well as making healthy choices. Managing Thalassemia Thalassemia is a treatable disorder that can be ...

  5. Healthy,Happy trees

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Healthy trees are important to us all. Trees provide shade, beauty, and homes for wildlife. Trees give us products like paper and wood. Trees can give us all this only if they are healthy.They must be well cared for to remain healthy.

  6. Healthy cities and healthy urban design

    OpenAIRE

    Drevland, Ingvill S.

    2016-01-01

    As an occupational therapist, I have always found the interaction between humans, their environment and their activities interesting, and how the environment can influence what we do and our occupational patterns is something that fascinates me. As my interest for urban health and healthy cities has grown during this master program, I have chosen to use the experience and knowledge I have from my field of expertise and put it in the context of healthy urban planning. This maste...

  7. Neurobiological implications of eating healthy.

    Science.gov (United States)

    Esch, Tobias; Kim, Jae Won; Stefano, George B

    2006-01-01

    Over the last decades, the importance of food in the development of chronic diseases has been examined, as well as the medical value of eating healthy. The contribution of the eating process itself to health and well-being, however, has not been questioned until most recently. Biology has linked eating to appetitive motivational processes with their underlying neurophysiology, including CNS reward circuitries: Eating uses the pleasure-reward physiology to motivate us to eat. Endogenous opiates, such as morphine, insure our survival by helping us to make eating motivational via pleasure induction. After taking in enough food, we become satisfied, i.e., tolerant to food. Our appetite, and so is our appetence, are then low and need a certain time span to reach their former levels for then inducing food-seeking behaviors, food intake, etc. again. When tolerance passes, we once more engage in this pleasurable process related to positive behavioral motivation. Opioid receptor agonists, however, may induce energy intake even beyond an actual need. This interesting potential of opioidergic signaling may have its roots in biological mechanisms that insured the intake and storage of high energy foods, hence preparing for future famines. In our world of today, however, such neurobiological pathways may pose a threat on our health. Thus, feedback mechanisms, such as tolerance, aversion and satiety, have to be finely tuned. Therefore central autoregulation that involves, for example, limbic mu receptor signaling and other endogenous signaling compounds comes into the focus of modern science. The time where research recognizes the importance of neurobiological pathways such as endogenous opiate autoregulation or CNS reward circuitries for examining the physiology of food intake has yet begun. Many questions remain open and have to be answered through future scientific inquiry.

  8. Action plan for healthy agriculture, healthy nutrition, healthy people

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2013-04-01

    Full Text Available In October 2010, the World Council on Genetics, Nutrition and Fitness for Health promoted a scientific meeting in Ancient Olympia, Greece, on the theme Healthy Agriculture, Healthy Nutrition, Healthy People. The meeting focused on evolutionary aspects of human diet through the life cycle in terms of genetic predisposition, overall health, prevention of disease and of unhealthy behaviors, such as poor physical activity, and dietary changes caused by the introduction of modern agriculture, from the Agribusiness to systems of food production, from climate changes to the needs imposed by urban agriculture and architecture. Nutritional medical (mostly cardiological and political aspects of disease prevention through healthy dietary habits and physical activity have always been seen in isolation. The meeting, the first of its kind, treated such aspects together, recognizing the importance of integrating and initiating a dialogue between these disciplines. The meeting gathered together experts in cardiovascular prevention, nutrition, as well as politicians, for a global discussion of these themes. A summary statement was then compiled, focusing on the main themes on which a consensus had been reached. I strongly believe that such themes have great relevance for public health, raising the need for disseminating them as widely as possible. I am thankful to the Editor of the Italian Journal of Medicine for allowing this summary document to be made available for the first time in Italy.Raffaele De Caterina

  9. State, religion and toleration

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2009-01-01

    Contribution to Religion and State - From separation to cooperation? Legal-philosophical reflections for a de-secularized world. (IVR Cracow Special Workshop). Eds. Bart. C. Labuschagne & Ari M. Solon. Abstract: Toleration is indeed a complex phenomenon. A discussion of the concept will have...... to underline not only the broadmindedness and liberty of individuals or of groups, but also the relevant distinctions and arguments in political philosophy, epistemology, philosophy of religion and philosophical anthropology and their connection with educational issues. Through a discussion of these relations......, the essay argues three theses: (1) Toleration is not reducible to an ethics of spiritual freedom. (2) Toleration is not neutral to fanatism. (3) Toleration involves esteem for the person....

  10. Heat tolerance in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari

    climate, wheat is sensitive to heat stress. We need to understand how our crops will perform in these changing climatic conditions and how we can develop varieties, which are more tolerant. The PhD study focussed on understanding heat tolerance in wheat with a combined approach of plant physiology...... II (PSII), which is a fundamental process in photosynthesis. The first study was conducted to identify cultivars differing in Fv/Fm as a measure of heat tolerance during reproductive phase. The proportion of the total variation in cultivar Fv/Fm that was due to the genotypic difference was termed...... among cultivars due to heat stress as the GD of most of them remained similar in control and stress. The second study investigated if it was possible to use detached leaves to screen for heat tolerance instead of intact plants. The previously selected 41 cultivars, known to differ in v/Fm, were used...

  11. [INABILITY TO TOLERATE COSMETICS].

    Science.gov (United States)

    Piérard, G E; Piérard-Franchimont, C

    2016-05-01

    Inability to tolerate cosmetics can result from distinct mechanisms which appear as the so-called sensitive skin corresponding to one aspect of invisible dermatosis, or which corresponds to manifestations of a contact allergic or irritation dermatitis.

  12. Desiccation tolerance of prokaryotes

    National Research Council Canada - National Science Library

    Potts, M

    1994-01-01

    ...) may be achieved rapidly. In the air-dried state some bacteria survive only for seconds whereas others can tolerate desiccation for thousands, perhaps millions, of years. The desiccated (anhydrobiotic...

  13. Fault-tolerant design

    CERN Document Server

    Dubrova, Elena

    2013-01-01

    This textbook serves as an introduction to fault-tolerance, intended for upper-division undergraduate students, graduate-level students and practicing engineers in need of an overview of the field.  Readers will develop skills in modeling and evaluating fault-tolerant architectures in terms of reliability, availability and safety.  They will gain a thorough understanding of fault tolerant computers, including both the theory of how to design and evaluate them and the practical knowledge of achieving fault-tolerance in electronic, communication and software systems.  Coverage includes fault-tolerance techniques through hardware, software, information and time redundancy.  The content is designed to be highly accessible, including numerous examples and exercises.  Solutions and powerpoint slides are available for instructors.   ·         Provides textbook coverage of the fundamental concepts of fault-tolerance; ·         Describes a variety of basic techniques for achieving fault-toleran...

  14. Tissue engineering for clinical applications.

    Science.gov (United States)

    Bhatia, Sujata K

    2010-12-01

    Tissue engineering is increasingly being recognized as a beneficial means for lessening the global disease burden. One strategy of tissue engineering is to replace lost tissues or organs with polymeric scaffolds that contain specialized populations of living cells, with the goal of regenerating tissues to restore normal function. Typical constructs for tissue engineering employ biocompatible and degradable polymers, along with organ-specific and tissue-specific cells. Once implanted, the construct guides the growth and development of new tissues; the polymer scaffold degrades away to be replaced by healthy functioning tissue. The ideal biomaterial for tissue engineering not only defends against disease and supports weakened tissues or organs, it also provides the elements required for healing and repair, stimulates the body's intrinsic immunological and regenerative capacities, and seamlessly interacts with the living body. Tissue engineering has been investigated for virtually every organ system in the human body. This review describes the potential of tissue engineering to alleviate disease, as well as the latest advances in tissue regeneration. The discussion focuses on three specific clinical applications of tissue engineering: cardiac tissue regeneration for treatment of heart failure; nerve regeneration for treatment of stroke; and lung regeneration for treatment of chronic obstructive pulmonary disease. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Tolerance doses for treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD/sub 5/) or 50% (TD/sub 50/) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs.

  16. Informing tendon tissue engineering with embryonic development

    OpenAIRE

    Glass, Zachary A.; Schiele, Nathan R.; Kuo, Catherine K

    2014-01-01

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies hav...

  17. Spectromicroscopy of Brain Tissue

    Science.gov (United States)

    Frazer, Bradley; Cannara, Rachel; Gilbert, Benjamin; Destasio, Gelsomina; Ogg, Mandy; Gough, Kathy

    2001-03-01

    X-ray PhotoElectron Emission Microscopy (X-PEEM) was originally developed for studying the surface microchemistry of materials science specimens. It has then evolved into a valuable tool to investigate the magnetic properties of materials and the microchemistry of cells and tissues. We used the MEPHISTO X-PEEM instrument, installed at the UW-Synchrotron Radiation Center to detect trace concentrations of non-physiological elements in senile brain tissue specimens. These tissues contain a large number of plaques, in which all the compounds and elements that the brain does not need are disposed and stored. We hypothesized that plaques should contain elements, such as Si, B, and Al which are very abundant on the Earth crust but absent from healthy tissues. We verified this hypothesis with MEPHISTO and found evidence of Si and B, and suspect Al. We also found a higher than normal concentration of Fe.

  18. CYCLOXYDIM-TOLERANT MAIZE – BREEDERS STANDPOINT

    Directory of Open Access Journals (Sweden)

    G. Bekavac

    2008-09-01

    Full Text Available Cycloxydim-Tolerant Maize (CTM was developed by researches at the University of Minnesota. CTM plants were regenerated from tissue culture selected for callus growth in the presence of cycloxydim, and the resulting plants were shown to contain a nuclear mutation, expressed as a single, partially dominant gene (known as Acc1 that conferred tolerance to the herbicide. Cycloxydim is a systemic herbicide for post emergence application in dicot crops to selectively control grass weeds. Corn, like most grasses is susceptible to cycloxydim due to inhibited acetyl-coenzyimeA carboxylaze enzyme activity. There are two key benefits of this technology: first, cycloxydim applications in CTM hybrids can be delayed until the weed spectrum and population density exceed agro-economic threshold; second, cycloxydim can be applied at either stage of plant development with no effect on basic agronomic traits, compared to non treated plants. Nevertheless, this type of tolerance requires 2 genes to be fully effective, i.e. gene must be present in both inbred parents to provide complete tolerance in the resulting hybrid. Such type of tolerance doubles the chances for yield drag and doubles the number of inbred conversions needed. This also limits germplasm integration and increases time lag in developing hybrids. Despite these difficulties, many seed companies introduce tolerance to cycloxydim into their commercial inbreds, and many of them have already commercialized CTM hybrids. Finally, it came as a logical question what is more important – hybrid performance or new trait? Critical to the success of this technology has been yield performance of CTM hybrids. At the same time, performance and herbicide tolerance do not exclude each other and can surely co-exist. To be accepted, this coexistence must secure high profitability to corn producers. However, CTM hybrids will not replace conventional ones on a large scale, but could be used as a specific tool, or could

  19. Are there still healthy obese patients?

    Science.gov (United States)

    Blüher, Matthias

    2012-10-01

    Obesity is associated with an increased risk of premature death and represents a fast growing worldwide health problem that is reaching epidemic proportions. Obesity significantly increases the risk of developing metabolic disorders, hypertension, coronary heart disease, stroke, and several types of cancer. However, a subgroup of 'healthy' obese patients seems to be protected against metabolic and cardiovascular obesity comorbidities. This review focuses on potential mechanisms underlying the healthy obese subphenotype. Individuals with obesity typically develop type 2 diabetes, dyslipidemia, fatty liver disease, gout, hypertension, and cardiovascular disease. In the past years it became clear that up to 30% of obese patients are metabolically healthy with insulin sensitivity similar to healthy lean individuals, lower liver fat content, and lower intima media thickness of the carotid artery than the majority of metabolically 'unhealthy' obese patients. Recent studies suggest that protection against development of hepatic steatosis, ectopic fat deposition, inflammation of visceral adipose tissue, and adipose tissue dysfunction contributes to healthy obesity. For the stratification of obesity treatment, definition of metabolically healthy or high-risk phenotypes will facilitate the identification of the obese person who will benefit the most from early lifestyle, bariatric surgery, or pharmacological interventions.

  20. Are there healthy obese?

    Science.gov (United States)

    Griera Borrás, José Luis; Contreras Gilbert, José

    2014-01-01

    It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  1. ADOLESCENTS’ HEALTHY EATING

    DEFF Research Database (Denmark)

    Pedersen, Susanne

    . As a follow-up on a healthy eating intervention, 38 adolescents and their respective families participated in depth-interviews and a practical exercise on daily fruit and vegetable intake. Results demonstrated that adolescents were found to adopt two strategies: a direct one placing demands on parents......This PhD thesis contributes with knowledge about adolescent healthy eating by studying consumer socialisation, social influence and behavioural change in relation to adolescent healthy eating. The introduction provides the important reasons for studying adolescents and healthy eating and explains...... that a more holistic approach is needed in order to respond to the rising levels of overweight among adolescents. It is important to understand the development of and influences on adolescent healthy eating behaviour and the possibilities for promoting healthy eating through interventions. By reviewing...

  2. Nosema spp. infections cause no energetic stress in tolerant honeybees

    DEFF Research Database (Denmark)

    Kurze, Christoph; Mayack, Christopher; Hirche, Frank

    2016-01-01

    Host-pathogen coevolution leads to reciprocal adaptations, allowing pathogens to increase host exploitation or hosts to minimise costs of infection. As pathogen resistance is often associated with considerable costs, tolerance may be an evolutionary alternative. Here, we examined the effect of tw...... as well as healthy bees, maintaining colony efficiency and productivity....

  3. Radiotherapy in patients with connective tissue diseases.

    Science.gov (United States)

    Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

    2016-03-01

    The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy.

  4. The pQCT 'Bone Strength Indices' (BSIs, SSI). Relative mechanical impact and diagnostic value of the indicators of bone tissue and design quality employed in their calculation in healthy men and pre- and post-menopausal women.

    Science.gov (United States)

    Cointry, G R; Ferretti, J L; Reina, P S; Nocciolino, L M; Rittweger, J; Capozza, R F

    2014-03-01

    The pQCT-assessed Bone Strength Indices (BSI's, SSI) depend on the product of a 'quality' indicator, the cortical vBMD (vCtD), and a 'design' indicator, one of the cross-sectional moments of inertia or related variables (MIs) in long bones. As the MIs vary naturally much more than the vCtD and represent different properties, it could be that the variation of the indices might not reflect the relative mechanical impact of the variation of their determinant factors in different individuals or circumstances. To understand this problem, we determined the vCtD and MI's in tibia scans of 232 healthy men and pre- and post-MP women, expressed in SD of the means calculated for each group, and analyzed the independent influence of 1 SD unit of variation of each factor on that of the indices by multiple correlations. Results showed: 1. that the independent influence of the MIs on the indices was generally larger than that of the vCtD, and 2. that in post-MP women the influence of the vCtD was larger than it was in the other groups. This confirms the view that inter-individual variation of vCtD is comparatively small, and that mechanical competence of human bone is mostly determined by 'design' factors.

  5. Mechanisms of Tolerance Induction by Hematopoietic Chimerism: The Immune Perspective.

    Science.gov (United States)

    Yolcu, Esma S; Shirwan, Haval; Askenasy, Nadir

    2017-03-01

    Hematopoietic chimerism is one of the effective approaches to induce tolerance to donor-derived tissue and organ grafts without administration of life-long immunosuppressive therapy. Although experimental efforts to develop such regimens have been ongoing for decades, substantial cumulative toxicity of combined hematopoietic and tissue transplants precludes wide clinical implementation. Tolerance is an active immunological process that includes both peripheral and central mechanisms of mutual education of coresident donor and host immune systems. The major stages include sequential suppression of early alloreactivity, establishment of hematopoietic chimerism and suppressor cells that sustain the state of tolerance, with significant mechanistic and temporal overlap along the tolerization process. Efforts to devise less toxic transplant strategies by reduction of preparatory conditioning focus on modulation rather than deletion of residual host immunity and early reinstitution of regulatory subsets at the central and peripheral levels. Stem Cells Translational Medicine 2017;6:700-712.

  6. Tolerable Intolerance: An Evolutionary Model

    OpenAIRE

    Martin Gregor

    2005-01-01

    A cornerstone of liberal-democratic regimes is the right of free speech, granted even to nonliberals who manifestly oppose it. Communism and political Islamism are two primary examples of ideologies which are tolerated in spite of calls for the limits on the right of expression. Not surprisingly, it is often argued that a tolerant society needs laws preventing non-tolerant beliefs from attacking tolerance. Yet, does intolerance necessarily prosper in a tolerant society, or is deemed to decay?...

  7. Tolerance to exercise intensity modulates pleasure when exercising in music: The upsides of acoustic energy for High Tolerant individuals

    Science.gov (United States)

    2017-01-01

    Moderate physical activity can be experienced by some as pleasurable and by others as discouraging. This may be why many people lack sufficient motivation to participate in the recommended 150 minutes of moderately intense exercise per week. In the present study, we assessed how pleasure and enjoyment were modulated differently by one’s tolerance to self-paced physical activity. Sixty-three healthy individuals were allocated to three independent experimental conditions: a resting condition (watching TV), a cycling in silence condition, and a cycling in music condition. The tolerance threshold was assessed using the PRETIE-Questionnaire. Physical activity consisted in cycling during 30 minutes, at an intensity perceived as “somewhat difficult” on the Ratings of Perceived Exertion Scale. While controlling for self-reported physical activity level, results revealed that for the same perception of exertion and a similar level of enjoyment, the High Tolerance group produced more power output than the Low Tolerance group. There was a positive effect of music for High Tolerant individuals only, with music inducing greater power output and more pleasure. There was an effect of music on heart rate frequency in the Low Tolerant individuals without benefits in power output or pleasure. Our results suggest that for Low Tolerant individuals, energizing environments can interfere with the promised (positive) distracting effects of music. Hence, tolerance to physical effort must be taken into account to conceive training sessions that seek to use distracting methods as means to sustain pleasurable exercising over time. PMID:28248980

  8. How Does Physical Activity Help Build Healthy Bones?

    Science.gov (United States)

    ... Publications How does physical activity help build healthy bones? Skip sharing on social media links Share this: Page Content ​​Bones are living tissue. Weight-bearing physical activity causes ...

  9. Informed consent in healthy volunteers: Whom does it protect?

    NARCIS (Netherlands)

    Van Vliet, A.A.; Wemer, J.; Wilffert, B.; De Vroedt, J.W.P.; Jonkman, J.H.G.

    1999-01-01

    In the next decade, centres for research on the safety, tolerability or bioequivalence of new molecular entities will be confronted with numerous compounds, a narrowing time frame for performing Phase I research activities, and a growing demand for healthy volunteers for participation in non-therape

  10. Healthy Homes Tools

    Science.gov (United States)

    Peek, Gina; Lyon, Melinda; Russ, Randall

    2012-01-01

    Extension is focusing on healthy homes programming. Extension educators are not qualified to diagnose consumers' medical problems as they relate to housing. We cannot give medical advice. Instead, we can help educate consumers about home conditions that may affect their well-being. Extension educators need appropriate healthy homes tools to…

  11. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  12. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  13. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  14. Active and Healthy Schools

    Science.gov (United States)

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  15. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of hu

  16. Tolerance and recognition

    Directory of Open Access Journals (Sweden)

    Hans Marius Hansteen

    2014-12-01

    Full Text Available Even though “toleration” and “recognition” designate opposing attitudes (to tolerate something, implies a negative stance towards it, whereas recognition seems to imply a positive one, the concepts do not constitute mutually exclusive alternatives. However, “toleration” is often associated with liberal universalism, focusing on individual rights, whereas “recognition” often connotes communitarian perspectives, focusing on relations and identity. This paper argues that toleration may be founded on recognition, and that recognition may imply toleration. In outlining a differentiated understanding of the relationship between toleration and recognition, it seems apt to avoid an all-to-general dichotomy between universalism and particularism or, in other words, to reach beyond the debate between liberalism and communitarianism in political philosophy.The paper takes as its starting point the view that the discussion on toleration and diversity in intercultural communication is one of the contexts where it seems important to get beyond the liberal/communitarian dichotomy. Some basic features of Rainer Forst’s theory of toleration and Axel Honneth’s theory of the struggle for recognition are presented, in order to develop a more substantial understanding of the relationship between the concepts of toleration and recognition. One lesson from Forst is that toleration is a normatively dependent concept, i.e., that it is impossible to deduce principles for toleration and its limits from a theory of toleration as such. A central lesson from Honneth is that recognition – understood as a basic human need – is always conflictual and therefore dynamic.Accordingly, a main point in the paper is that the theory of struggles for and about recognition (where struggles for designates struggles within an established order of recognition, and struggles about designates struggles that challenge established orders of recognition may clarify what

  17. Den liberale tolerance

    DEFF Research Database (Denmark)

    Mchangama, Jacob; Andersen, Rasmus Fonnesbæk

    2012-01-01

    Tolerance er en kerneværdi i den liberal-demokratiske samfundsordenen, men i vor tid er det liberale tolerancebegreb om ikke at gribe ind i det, man ikke synes om, kommet under angreb fra flere sider, især som følge af problemer med indvandring og integration. Tolerance opfattes i stigende grad som...... begrænset tolerancebegreb igen bør træde i stedet for den multikulturalistisk inspirerede forståelse af tolerance, som er fremtrædende i dag, og som faktisk begrunder en institutionaliseret intolerance i form af en række begrænsninger på særligt ytringsfriheden....

  18. Measurement of ambiguity tolerance.

    Science.gov (United States)

    Norton, R W

    1975-12-01

    Presented definitions for the construct of ambiguity tolerance. The measure of ambiguity tolerance (MAT-50) had high internal reliability (r = .88) and high test-retest reliability (r = .86) over a 10-to-12 week period. A content analysis of the measure and a subjective analysis by 20 graduate students indicated adequate content validity. A multivariate comparison with two other ambiguity measures, two rigidity measures, and a short dogmatism measure provided strong evidence for criteria-related validity. Finally, four independent empirical studies showed good construct validity.

  19. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  20. Fault tolerant linear actuator

    Science.gov (United States)

    Tesar, Delbert

    2004-09-14

    In varying embodiments, the fault tolerant linear actuator of the present invention is a new and improved linear actuator with fault tolerance and positional control that may incorporate velocity summing, force summing, or a combination of the two. In one embodiment, the invention offers a velocity summing arrangement with a differential gear between two prime movers driving a cage, which then drives a linear spindle screw transmission. Other embodiments feature two prime movers driving separate linear spindle screw transmissions, one internal and one external, in a totally concentric and compact integrated module.

  1. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2013-01-01

    Under conditions of pluralism different cultures, interests or values can come into conflict, which raises the problem of how to secure peaceful co-existence. The idea of toleration historically emerged as an answer to this problem. Recently Rainer Forst has argued that toleration should not just...... prescription, which Forst presents as a requirement of justice. At both levels, it is argued that Forst’s respect conception is problematic since it presupposes that answers to very substantial normative questions, which are precisely what people tend to disagree on under conditions of pluralism, are already...

  2. A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Morris Peter E

    2012-02-01

    Full Text Available Abstract Background The tissue factor (TF-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS. Methods This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO2/FiO2 ≤ 300 mm. Eighteen patients (6 per cohort were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters. Results Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population. Conclusions Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS. Trial registration ClinicalTrials.gov: NCT01438853

  3. Growth hormone ameliorates adipose dysfunction during oxidative stress and inflammation and improves glucose tolerance in obese mice.

    Science.gov (United States)

    Fukushima, M; Okamoto, Y; Katsumata, H; Ishikawa, M; Ishii, S; Okamoto, M; Minami, S

    2014-08-01

    Patients with adult growth hormone deficiency exhibit visceral fat accumulation, which gives rise to a cluster of metabolic disorders such as impaired glucose tolerance and dyslipidemia. Plasma growth hormone levels are lower in obese patients with metabolic syndrome than in healthy subjects. Here we examined the hypothesis that exogenous growth hormone administration regulates function of adipose tissue to improve glucose tolerance in diet-induced obese mice. Twelve-week-old obese male C57BL/6 J mice received bovine growth hormone daily for 6 weeks. In epididymal fat, growth hormone treatment antagonized diet-induced changes in the gene expression of adiponectin, leptin, and monocyte chemoattractant protein-1, and significantly increased the gene expression of interleukin-10 and CD206. Growth hormone also suppressed the accumulation of oxidative stress marker, thiobarbituric acid-reactive substances, in the epididymal fat and enhanced the gene expression of anti-oxidant enzymes. Moreover, growth hormone significantly restored glucose tolerance in obese mice. In cultured 3T3-L1 adipocytes, growth hormone prevented the decline in adiponectin gene expression in the presence of hydrogen peroxide. These results suggest that growth hormone administration ameliorates glucose intolerance in obese mice presumably by decreasing adipose mass, oxidative stress, and chronic inflammation in the visceral fat.

  4. Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients.

    Science.gov (United States)

    Cutler, N R

    2001-01-01

    In clinical trials of dopamine-blocking antipsychotics, significant adverse events may occur in healthy volunteers at dose levels that are well tolerated by schizophrenic patients. Because of these differences in tolerability, bioequivalence and pharmacokinetic studies of antipsychotics should be performed in schizophrenic patients rather than in healthy volunteers. When clozapine is the drug being investigated, pharmacokinetic and bioequivalence studies should be carried out in real-life dosage conditions because the half-life of clozapine increases with multiple doses. Under real-life conditions, the evaluation of multiple doses of clozapine in a population of schizophrenic patients can provide direct therapeutic relevance to bioavailability findings. This article discusses patient recruitment and informed consent in pharmacokinetic trials of schizophrenia, issues in studying antipsychotic agents in healthy volunteers versus schizophrenic patients, and a bioequivalency study of Clozaril (Novartis Pharmaceuticals) and generic clozapine (Creighton [Sandoz]) in schizophrenic patients.

  5. A little toleration, please

    Science.gov (United States)

    McKnight, C.

    2000-01-01

    Value pluralism does not imply relativism or subjectivism about values. What it does is allow respect for an at least limited toleration of values with which one may profoundly disagree. Thus a doctor can respect the autonomy of a patient whose values he does not share. Key Words: Pluralism • multiculturalism • relativism • subjectivism • patient autonomy PMID:11129842

  6. Adaptive Fault Tolerance

    Science.gov (United States)

    1994-05-01

    center ( MOCl ) and one workstation processor (WS1) in the Adaptive Fault Tolerance 22 command center (CCE). The remaining data processing routines (GDI...78243-7063 NRAIR232 ATTN: DANIEL W. ATKINSON 9800 SAVAGE RD FT MEADE MD 20755-6000 TRUSTED INFORMATION SYSTEMS, INC. ATTN: WILLIAM C. BARKER 3060

  7. Tolerance through Exposure.

    Science.gov (United States)

    Russo, Carolyn

    In this project, eighth grade students are exposed to black history, literature, music, and art to enhance the understanding of diversity and to establish an atmosphere of tolerance for diversity. Students are asked to choose a personality or significant historical event to research and present to the class. They focus on issues such as prejudice,…

  8. 3HP tolerance

    DEFF Research Database (Denmark)

    2014-01-01

    Cells and cell cultures are provided that have improved tolerance to 3-hydroxypropionic acid (3HP). Genetic modifications to provide a mutated or overexpressed SFA1 gene or other enhancement of 3HP detoxification via a glutathione- dependent dehydrogenase reaction, including medium supplementation...

  9. Toleration and its enemies

    DEFF Research Database (Denmark)

    Jarvad, Ib Martin

    2010-01-01

    After a presentation of the development of freedom of expression in Danish constitutional law, to freedom of the press in European human rights law - the Jersild case- to a right to mock and ridicule other faiths in recent Danish practice, the essay of Locke on toleration is examined, its...

  10. Fault Tolerant Control Systems

    DEFF Research Database (Denmark)

    Bøgh, S. A.

    was to avoid a total close-down in case of the most likely faults. The second was a fault tolerant attitude control system for a micro satellite where the operation of the system is mission critical. The purpose was to avoid hazardous effects from faults and maintain operation if possible. A method...

  11. Tissue tests

    NARCIS (Netherlands)

    Sonneveld, C.; Voogt, W.

    2009-01-01

    Tissue tests are widely used in horticulture practice and have in comparison with soil or substrate testing advantages as well disadvantages in comparison with soil testing. One of the main advantages of tissue tests is the certainty that analysed nutrients in plant tissues are really present in the

  12. Tissue tests

    NARCIS (Netherlands)

    Sonneveld, C.; Voogt, W.

    2009-01-01

    Tissue tests are widely used in horticulture practice and have in comparison with soil or substrate testing advantages as well disadvantages in comparison with soil testing. One of the main advantages of tissue tests is the certainty that analysed nutrients in plant tissues are really present in the

  13. Ethanol tolerance in yeasts.

    Science.gov (United States)

    Casey, G P; Ingledew, W M

    1986-01-01

    It is now certain that the inherent ethanol tolerance of the Saccharomyces strain used is not the prime factor regulating the level of ethanol that can be produced in a high sugar brewing, wine, sake, or distillery fermentation. In fact, in terms of the maximum concentration that these yeasts can produce under batch (16 to 17% [v/v]) or fed-batch conditions, there is clearly no difference in ethanol tolerance. This is not to say, however, that under defined conditions there is no difference in ethanol tolerance among different Saccharomyces yeasts. This property, although a genetic determinant, is clearly influenced by many factors (carbohydrate level, wort nutrition, temperature, osmotic pressure/water activity, and substrate concentration), and each yeast strain reacts to each factor differently. This will indeed lead to differences in measured tolerance. Thus, it is extremely important that each of these be taken into consideration when determining "tolerance" for a particular set of fermentation conditions. The manner in which each alcohol-related industry has evolved is now known to have played a major role in determining traditional thinking on ethanol tolerance in Saccharomyces yeasts. It is interesting to speculate on how different our thinking on ethanol tolerance would be today if sake fermentations had not evolved with successive mashing and simultaneous saccharification and fermentation of rice carbohydrate, if distillers' worts were clarified prior to fermentation but brewers' wort were not, and if grape skins with their associated unsaturated lipids had not been an integral part of red wine musts. The time is now ripe for ethanol-related industries to take advantage of these findings to improve the economies of production. In the authors' opinion, breweries could produce higher alcohol beers if oxygenation (leading to unsaturated lipids) and "usable" nitrogen source levels were increased in high gravity worts. White wine fermentations could also, if

  14. Deconstructing tolerance with clobazam

    Science.gov (United States)

    Wechsler, Robert T.; Sankar, Raman; Montouris, Georgia D.; White, H. Steve; Cloyd, James C.; Kane, Mary Clare; Peng, Guangbin; Tworek, David M.; Shen, Vivienne; Isojarvi, Jouko

    2016-01-01

    Objective: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Methods: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg−1·d−1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg−1·d−1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Results: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Conclusions: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. ClinicalTrials.gov identifier: NCT00518713 and NCT01160770. Classification of evidence: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. PMID:27683846

  15. Persimmon leaf flavonoid promotes brain ischemic tolerance**

    Institute of Scientific and Technical Information of China (English)

    Mingsan Miao; Xuexia Zhang; Ming Bai; Linan Wang

    2013-01-01

    Persimmon leaf flavonoid has been shown to enhance brain ischemic tolerance in mice, but its mechanism of action remains unclear. The bilateral common carotid arteries were occluded using a micro clip to block blood flow for 10 minutes. After 10 minutes of ischemic preconditioning, 200, 100, and 50 mg/kg persimmon leaf flavonoid or 20 mg/kg ginaton was intragastrical y administered per day for 5 days. At 1 hour after the final administration, ischemia/reperfusion models were estab-lished by blocking the middle cerebral artery for 2 hours. At 24 hours after model establishment, compared with cerebral ischemic rats without ischemic preconditioning or drug intervention, plasma endothelin, thrombomodulin and von Wil ebrand factor levels significantly decreased and intercel-lular adhesion molecule-1 expression markedly reduced in brain tissue from rats with ischemic pre-conditioning. Simultaneously, brain tissue injury reduced. Ischemic preconditioning combined with drug exposure noticeably improved the effects of the above-mentioned indices, and the effects of 200 mg/kg persimmon leaf flavonoid were similar to 20 mg/kg ginaton treatment. These results indicate that ischemic preconditioning produces tolerance to recurrent severe cerebral ischemia. However, persimmon leaf flavonoid can elevate ischemic tolerance by reducing inflammatory reactions and vascular endothelial injury. High-dose persimmon leaf flavonoid showed an identical effect to ginaton.

  16. Computerized cuff pressure algometry: A new method to assess deep-tissue hypersensitivity in fibromyalgia.

    Science.gov (United States)

    Jespersen, Anders; Dreyer, Lene; Kendall, Sally; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars; Bliddal, Henning; Danneskiold-Samsoe, Bente

    2007-09-01

    The aim of this study was to evaluate the use of computerized cuff pressure algometry (CPA) in fibromyalgia (FM) and to correlate deep-tissue sensitivity assessed by CPA with other disease markers of FM. Forty-eight women with FM and 16 healthy age-matched women were included. A computer-controlled, pneumatic tourniquet cuff was placed over the gastrocnemius muscle. The cuff was inflated, and the subject rated the pain intensity continuously on an electronic Visual Analogue Scale (VAS). The subject stopped the inflation at the pressure-pain tolerance and the corresponding VAS-score was determined (pressure-pain limit). The pressure at which VAS firstly exceeded 0 was defined as the pressure-pain threshold. Other disease markers (FM only): Isokinetic knee muscle strength, tenderpoint-count, myalgic score, Beck Depression Inventory, and Fibromyalgia Impact Questionnaire. Student's T-test was used to compare pressure-pain threshold and pressure-pain tolerance and the Mann-Whitney test to compare pressure-pain limit. Pearson's correlation was used to detect linear relationships. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in FM compared to healthy controls. There was no difference in pressure-pain limit. CPA-parameters were significantly correlated to isokinetic muscle strength where more hypersensitivity resulted in lower strength. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in patients with FM indicating muscle hyperalgesia. CPA was associated with knee muscle strength but not with measures thought to be influenced by psychological distress and mood.

  17. Tissue engineering the kidney.

    Science.gov (United States)

    Hammerman, Marc R

    2003-04-01

    The means by which kidney function can be replaced in humans include dialysis and renal allotransplantation. Dialytic therapies are lifesaving, but often poorly tolerated. Transplantation of human kidneys is limited by the availability of donor organs. During the past decades, a number of different approaches have been applied toward tissue engineering the kidney as a means to replace renal function. The goals of one or another of them included the recapitulation of renal filtration, reabsorptive and secretory functions, and replacement of endocrine/metabolic activities. This review will delineate the progress to date recorded for five approaches: (1) integration of new nephrons into the kidney; (2) growing new kidneys in situ; (3) use of stem cells; (4) generation of histocompatible tissues using nuclear transplantation; and (5) bioengineering of an artificial kidney. All five approaches utilize cellular therapy. The first four employ transplantation as well, and the fifth uses dialysis.

  18. Heart-Healthy Exercise

    Science.gov (United States)

    ... American Heart Association Cardiology Patient Page Heart-Healthy Exercise Lauren Healey Mellett , Gisele Bousquet Download PDF https:// ... if you already have heart disease. How Can Exercise Help? There are many modifiable risk factors for ...

  19. Getting Healthy Scientifically

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Recently,Zhao Zhixin,a Beijing-based instructor on scientific bodybuilding and public sport,was interviewed by China Youth Daily,sharing his views on how to get healthy scientifically.Edited excerpts follow:

  20. Healthy Living after Stroke

    Science.gov (United States)

    ... Stories Stroke Heroes Among Us Healthy Living After Stroke Nutrition Good nutrition is one way to reduce ... look to maintain health and wellness. Subscribe to Stroke Connection Get quarterly digital issues plus our monthly ...

  1. Healthy Joints Matter

    Science.gov (United States)

    ... my joints more healthy? Definitions What can go wrong? Although you might think arthritis affects only older ... Discovery Into Health ® Home | Health Information | Research | Funding | News & Events | About Us | Portal en español | Asian-Language ...

  2. Healthy Eating and Pregnancy

    Science.gov (United States)

    ... Situations Pets and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight Loss and Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics Sports Safety Injury Rehabilitation Emotional Well- ...

  3. Healthy Watersheds Protection

    Science.gov (United States)

    Jump to main content US EPA United States Environmental Protection Agency Search Search Healthy Watersheds Protection (HWP) Share ... live in a watershed — thus watershed condition is important to everyone. Watersheds exist at different geographic scales, ...

  4. Healthy Ride Trip Data

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A dataset that shows trips taken using the Healthy Ride system by quarter. The dataset includes bike number, membership type, trip start and end timestamp, and...

  5. Healthy Conflict Management

    OpenAIRE

    Brower, Naomi

    2012-01-01

    Without healthy conflict management skills, conflict can often escalate or intensify over time. This fact sheet gives tips on utilizing key negotiation skills to help individuals effectively address and cope with conflict and potentially build stronger relationships with others.

  6. Planning For a Healthy School Year: Healthy Eating

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Planning For A Healthy School Year Healthy Eating Past ... are one of the first items. Read More "Planning For A Healthy School Year" Articles Back to ...

  7. Healthy Lean Through HRD

    DEFF Research Database (Denmark)

    Jørgensen, Frances

    2008-01-01

    The paper reports on findings from the initial, exploratory phase of a longitudinal research study aimed at developing a framework for implementing lean while ensuring employee well-being. Data from observations and in-depth dialogues with persons involved in lean implementation, along...... with relevant theory, are used to construct a tentative framework for implementing "healthy lean". The role of HRD in facilitating implementation of healthy lean is central to the framework, which is presented and discussed....

  8. Review of Tolerance of Ambiguity

    Institute of Scientific and Technical Information of China (English)

    王爽爽

    2015-01-01

    In this paper, definitions of tolerance of ambiguity both at home and abroad are reviewed first. Then studies of tolerance of ambiguity and foreign language teaching both home and abroad are introduced. At last, the paper proposed that it is of great sig⁃nificance and practicality for us to make further studies on tolerance of ambiguity.

  9. Impaired glucose tolerance in sleep disorders.

    Directory of Open Access Journals (Sweden)

    Marietta Keckeis

    Full Text Available BACKGROUND: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders. METHODOLOGY/PRINCIPAL FINDINGS: We performed oral glucose tolerance tests (OGTT and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25, restless legs syndrome (RLS, N = 18 or primary insomnia (N = 21, and in healthy controls (N = 33. Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9 and RLS (OR: 4.7 patients, but not in primary insomnia patients (OR: 1.6. In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05 and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05, respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases.

  10. Smart Substitutions for Healthy Cooking

    Science.gov (United States)

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Smart Substitutions Updated:Dec 16,2016 Healthy eating doesn’ ... mean giving up all the foods you love! Smart substitutions can help you maintain an overall healthy ...

  11. National Center for Healthy Housing

    Science.gov (United States)

    ... Resources Search NCHH Resources Ask NCHH Blog Building Materials and Products Consumer Survey Healthcare Financing How Can We Help You? Additional Resources Healthy Housing Clearinghouse Healthy Housing Links Healthy Housing Videos Lead ...

  12. Healthy habits for weight loss

    Science.gov (United States)

    ... gov/ency/patientinstructions/000733.htm Healthy habits for weight loss To use the sharing features on this page, ... to think about it. People who succeed at weight loss, turn healthy eating into a habit. These healthy ...

  13. Abuse Tolerance Improvements

    Energy Technology Data Exchange (ETDEWEB)

    Orendorff, Christopher J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Nagasubramanian, Ganesan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Fenton, Kyle R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Allcorn, Eric [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-10-01

    As lithium-ion battery technologies mature, the size and energy of these systems continues to increase (> 50 kWh for EVs); making safety and reliability of these high energy systems increasingly important. While most material advances for lithium-ion chemistries are directed toward improving cell performance (capacity, energy, cycle life, etc.), there are a variety of materials advancements that can be made to improve lithium-ion battery safety. Issues including energetic thermal runaway, electrolyte decomposition and flammability, anode SEI stability, and cell-level abuse tolerance continue to be critical safety concerns. This report highlights work with our collaborators to develop advanced materials to improve lithium-ion battery safety and abuse tolerance and to perform cell-level characterization of new materials.

  14. Damage Tolerance Assessment Branch

    Science.gov (United States)

    Walker, James L.

    2013-01-01

    The Damage Tolerance Assessment Branch evaluates the ability of a structure to perform reliably throughout its service life in the presence of a defect, crack, or other form of damage. Such assessment is fundamental to the use of structural materials and requires an integral blend of materials engineering, fracture testing and analysis, and nondestructive evaluation. The vision of the Branch is to increase the safety of manned space flight by improving the fracture control and the associated nondestructive evaluation processes through development and application of standards, guidelines, advanced test and analytical methods. The Branch also strives to assist and solve non-aerospace related NDE and damage tolerance problems, providing consultation, prototyping and inspection services.

  15. Socially-Tolerable Discrimination

    OpenAIRE

    J. Atsu Amegashie

    2008-01-01

    History is replete with overt discrimination of various forms. However, these forms of discrimination are not equally tolerable. For example, discrimination based on immutable or prohibitively unalterable characteristics such as race or gender is much less acceptable. Why? I develop a simple model of conflict which is driven by either racial (gender) discrimination or generational discrimination (i.e., young versus old). I show that there exist parameters of the model where racial (gender) di...

  16. Drought Tolerance in Wheat

    Directory of Open Access Journals (Sweden)

    Arash Nezhadahmadi

    2013-01-01

    Full Text Available Drought is one of the most important phenomena which limit crops’ production and yield. Crops demonstrate various morphological, physiological, biochemical, and molecular responses to tackle drought stress. Plants’ vegetative and reproductive stages are intensively influenced by drought stress. Drought tolerance is a complicated trait which is controlled by polygenes and their expressions are influenced by various environmental elements. This means that breeding for this trait is so difficult and new molecular methods such as molecular markers, quantitative trait loci (QTL mapping strategies, and expression patterns of genes should be applied to produce drought tolerant genotypes. In wheat, there are several genes which are responsible for drought stress tolerance and produce different types of enzymes and proteins for instance, late embryogenesis abundant (lea, responsive to abscisic acid (Rab, rubisco, helicase, proline, glutathione-S-transferase (GST, and carbohydrates during drought stress. This review paper has concentrated on the study of water limitation and its effects on morphological, physiological, biochemical, and molecular responses of wheat with the possible losses caused by drought stress.

  17. Chitinase Activity in Healthy and Sclerotium rolfsii Infected Peanut

    Directory of Open Access Journals (Sweden)

    ENDANG PUDJIHARTATI

    2006-06-01

    Full Text Available The objectives of this experiment were to analyze the endo- or exo-chitinase activities of healthy and Sclerotium rolfsii infected peanuts. The experiment analyzed 24 different peanut genotypes. Results of the experiment showed chromogenic dimer was the most suitable substrate for analysing chitinase activities. Both endo- and exo-chitinases activities were detected in leaf, stem, and crown tissues. Increased in chitinase activities were detected in S. rolfsii infected peanut tissues than in healthy plant. Regression analysis showed negative slope between disease intensity and chitinase activity in S. rolfsii infected peanut tissue (R2= 0.45.

  18. Colonization, safety, and tolerability study of the Streptococcus salivarius 24SMBc nasal spray for its application in upper respiratory tract infections.

    Science.gov (United States)

    Santagati, M; Scillato, M; Muscaridola, N; Metoldo, V; La Mantia, I; Stefani, S

    2015-10-01

    Streptococcus salivarius, a non-pathogenic species and the predominant colonizer of the oral microbiota, finds a wide application in the prevention of upper respiratory tract infections, also reducing the frequency of their main pathogens. In this pilot study, the primary objective was to evaluate the safety and tolerability of a nasal spray, S. salivarius 24SMBc, as a medical device in a clinical study involving 20 healthy adult subjects. The secondary aim was to determine the ability of colonization assessed by molecular fingerprinting. Twenty healthy adult subjects, aged between 30 and 54 years, without a medical history of recurrent otitis media, were enrolled. All patient characteristics fulfilled the inclusion criteria. All subjects were treated daily for 3 days with the nasal spray containing S. salivarius 24SMBc at a concentration of 5 × 10(9) colony-forming units (CFU)/ml. The persistence of S. salivarius in the nasopharynx was investigated by the antagonism test and random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). The tolerability and safety were clinically assessed by clinical examinations during treatment. Our results demonstrate the capability of S. salivarius 24SMBc to colonize the rhinopharynx tissues in 95% of subjects and persist in 55% of them after 6 days from the last dose of the formulation, maintaining a concentration of 10(5) CFU/ml. The treatment was well tolerated by all healthy patients and no adverse effects were found. The topical application of streptococcal probiotics is a relatively undeveloped field but is becoming an attractive approach for both prevention and therapy, especially for pediatric age patients. S. salivarius 24SMBc possess characteristics making this strain suitable for use in bacteriotherapy.

  19. Tissue types (image)

    Science.gov (United States)

    There are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue ... and binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of ...

  20. A Healthy Person

    Science.gov (United States)

    Høye, Sevald; Kvigne, Kari; Aiyub, Ilyas; Gillund, Margrethe V.; Hermansyah, Hasan; Nordström, Gun; Rystedt, Ingrid; Suwarni, Abubakar; Trollvik, Anne; Wilde-Larsson, Bodil; Hov, Reidun

    2016-01-01

    The purpose of this exploratory study was to investigate how nursing students in Indonesia and Scandinavia characterize a healthy person. Two hundred thirty-two nursing students from Indonesia, 50 students from Sweden, and 119 students from Norway participated by answering an open-ended question. Qualitative content analysis was used to identify patterns of health in a cultural and national context. The characteristics of a healthy person were summarized in the theme “external and inner balance,” which are intertwined because of the wholeness of self-image and appearance. The subcategories were having a strong and positive body image, feeling well and having inner harmony, following the rules of life, coping with challenges, and acting in unison with the environment. There were more similarities than differences between the Indonesian and Scandinavian nursing students’ understanding of being a healthy person. The difference is that the Scandinavian students mentioned individuality, whereas the Indonesian students referred to collective values. PMID:28462342

  1. Sex differences and plasticity in dehydration tolerance: insight from a tropical liverwort

    OpenAIRE

    Marks, Rose A.; Burton, James F.; McLetchie, D. Nicholas

    2016-01-01

    Background and Aims Adaptations allowing plants to cope with drying are particularly relevant in the light of predicted climate change. Dehydration tolerance (DhT, also dehydration-tolerant) is one such adaptation enabling tissue to survive substantial drying. A great deal of work has been conducted on highly DhT species. However, bryophytes showing less intense and variable DhT are understudied, despite the potential for these species to provide an informative link between highly tolerant an...

  2. Preclinical investigation of tolerance and antitumour activity of new fluorodeoxyglucose-coupled chlorambucil alkylating agents.

    Science.gov (United States)

    Miot-Noirault, Elisabeth; Reux, Bastien; Debiton, Eric; Madelmont, Jean-Claude; Chezal, Jean-Michel; Coudert, Pascal; Weber, Valérie

    2011-06-01

    Our strategy is to increase drug accumulation in target tumour cells using specific "vectors" tailored to neoplastic tissue characteristics, which ideally are not found in healthy tissues. The aim of this work was to use 2-fluoro-2-deoxyglucose (FDG) as a drug carrier, in view of its well-known accumulation by most primary and disseminated human tumours. We had previously selected two FDG-cytotoxic conjugates of chlorambucil (CLB), i.e. compounds 21a and 40a, on the basis of their in vitro profiles. Here we investigated the antitumour profile and tolerance of these compounds in vitro and in vivo in two murine cell lines of solid tumours. In vitro, we found that micromolar concentrations of compounds 21a and 40a inhibited proliferation of B16F0 and CT-26 cell lines. Interestingly, compounds 21a and 40a were found to act at different levels in the cell cycle: S and subG1 accumulation for 21a and G2 accumulation for 40a. In vivo, a single-dose-finding study to select the Maximum Tolerated Dose (MTD) by the intraperitoneal route (IP) showed that the two peracetylated glucoconjugates of CLB were less toxic than CLB itself. When given to tumour-bearing mice (melanoma and colon carcinoma models), according to a "q4d × 3" schedule (i.e., three doses at 4-day intervals) both compounds demonstrated a promising antitumour activity, with Log Cell Kill (LCK) values higher than 1.3 in both B16F0 and CT-26 models. Hence compounds 21a and 40a are good candidates for further works to develop new highly active antineoplastic compounds.

  3. Quality assurances and tolerances

    Energy Technology Data Exchange (ETDEWEB)

    Kirschling, G.

    1991-12-31

    This book presents a comprehensive statistical solution to tolerance problems to be used as an alternative to the conventional arithmetic approach that is used for tolerancing. The book is a translation from an original text in German. The classificatio nof the book would be as a reference text for engineers who are working in the production and quality control fields, particularly in process control. Academics who are teaching such subjects as statistical process control of geometric dimensioning and tolerancing will also find the book useful.

  4. Fault Tolerant Computer Architecture

    CERN Document Server

    Sorin, Daniel

    2009-01-01

    For many years, most computer architects have pursued one primary goal: performance. Architects have translated the ever-increasing abundance of ever-faster transistors provided by Moore's law into remarkable increases in performance. Recently, however, the bounty provided by Moore's law has been accompanied by several challenges that have arisen as devices have become smaller, including a decrease in dependability due to physical faults. In this book, we focus on the dependability challenge and the fault tolerance solutions that architects are developing to overcome it. The two main purposes

  5. Desiccation tolerance of prokaryotes.

    Science.gov (United States)

    Potts, M

    1994-12-01

    The removal of cell-bound water through air drying and the addition of water to air-dried cells are forces that have played a pivotal role in the evolution of the prokaryotes. In bacterial cells that have been subjected to air drying, the evaporation of free cytoplasmic water (Vf) can be instantaneous, and an equilibrium between cell-bound water (Vb) and the environmental water (vapor) potential (psi wv) may be achieved rapidly. In the air-dried state some bacteria survive only for seconds whereas others can tolerate desiccation for thousands, perhaps millions, of years. The desiccated (anhydrobiotic) cell is characterized by its singular lack of water--with contents as low as 0.02 g of H2O g (dry weight)-1. At these levels the monolayer coverage by water of macromolecules, including DNA and proteins, is disturbed. As a consequence the mechanisms that confer desiccation tolerance upon air-dried bacteria are markedly different from those, such as the mechanism of preferential exclusion of compatible solutes, that preserve the integrity of salt-, osmotically, and freeze-thaw-stressed cells. Desiccation tolerance reflects a complex array of interactions at the structural, physiological, and molecular levels. Many of the mechanisms remain cryptic, but it is clear that they involve interactions, such as those between proteins and co-solvents, that derive from the unique properties of the water molecule. A water replacement hypothesis accounts for how the nonreducing disaccharides trehalose and sucrose preserve the integrity of membranes and proteins. Nevertheless, we have virtually no insight into the state of the cytoplasm of an air-dried cell. There is no evidence for any obvious adaptations of proteins that can counter the effects of air drying or for the occurrence of any proteins that provide a direct and a tangible contribution to cell stability. Among the prokaryotes that can exist as anhydrobiotic cells, the cyanobacteria have a marked capacity to do so. One

  6. Healthy Drinks for Kids

    Science.gov (United States)

    ... For Kids For Parents MORE ON THIS TOPIC Caffeine Calcium Sports and Energy Drinks: Should Your Child Drink Them? What Should Preschoolers ... Why Drinking Water Is the Way to Go Caffeine Confusion What's a Healthy Alternative to Water? Energy Drinks and Food Bars: Power or Hype? A Guide ...

  7. Getting Healthy Scientifically

    Institute of Scientific and Technical Information of China (English)

    Zhao Zhixin

    2010-01-01

    @@ Recently, Zhao Zhixin, a Beijing-based instructor on scientific bodybuiiding and public sport,was interviewed by China Youth Daily, sharing his views on how to get healthy scientifically.Edited excerpts follow: China Youth Daily: What do you think about food therapy as a regimen?

  8. Tips for Healthy Voices

    Science.gov (United States)

    ... social interaction as well as for most people’s occupation. Proper care and use of your voice will give you the best chance for having a healthy voice for your entire lifetime. Hoarseness or roughness in your voice is often ...

  9. Some like it healthy

    DEFF Research Database (Denmark)

    Contini, Caterina; Casini, Leonardo; Stancu, Violeta

    2015-01-01

    Authorising new health claims in Europe will favour the diffusion on the market of a greater number of foods with health claims. This scenario presents new opportunities to promote healthy food choices and launches new challenges to define strategies aimed at promoting products on the market. The...

  10. The Healthy Eating Pyramid

    Institute of Scientific and Technical Information of China (English)

    Jimmy; Lin

    2007-01-01

    Experts from the Harvard School of Public Health created the Healthy Eating Pyramid.The pyramid is about the links between diet and health and offers useable information to help people make better choices about what to eat. Remember:its base is daily exercise and weight control.

  11. Making Healthy Sexual Decisions

    Science.gov (United States)

    ... including your partner) ? Is your decision to have sex based on the right reasons? (It shouldn’t be based on peer ... re ready! Tags: birth control , condoms , contraception , healthy sex , peer ... Contraception (EC) Sexual Orientation and Gender Identity: General Information How do I ...

  12. Alternative Promoter Usage in Healthy and Inflamed Tissue

    DEFF Research Database (Denmark)

    Lilje, Berit

    With the introduction of high throughput sequencing, it became possible to simultaneously study all transcribed genes in an unbiased manner. Sequence-based gene expression methods works by extracting and sequencing all transcripts present in a cell population. One such method is Cap Analysis of G...

  13. The pharmacokinetics of intravenous fenoldopam in healthy, awake cats.

    Science.gov (United States)

    O'Neill, K E; Labato, M A; Court, M H

    2016-04-01

    Fenoldopam is a selective dopamine-1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well-tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of fenoldopam. Six healthy, awake, client-owned cats aged 2-6 years old received a 120-min constant rate infusion of fenoldopam at 0.8 μg/kg/min followed by a 20-min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half-life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 μg/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of fenoldopam in cats with kidney disease is recommended. © 2016 John Wiley & Sons Ltd.

  14. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

  15. Ethnopoly promotes tolerance

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    On Friday 23 April, 225 primary school children from the eight schools in Meyrin-Cointrin and their accompanying adults took part in a big game of Ethnopoly. Private individuals, associations, administrations, shopkeepers and CERN all opened their doors to them to talk about their countries, their customs and what they are doing to promote tolerance and integration.   The CERN stand set up at ForumMeyrin for the Ethnopoly game. Scurrying from one place to another, the 10 and 11 year olds were made aware of the rich cultural diversity of their commune, which is home to 130 different nationalities. Physicists and engineers from CERN took up residence in the Forum Meyrin for the day in order to talk to the children about the advantages of international collaboration, a subject dear to the Organization's heart. They welcomed around fifty children in the course of the day, conveying to them a message of tolerance: despite their differences, the 10,000 scientists and other members of the CERN...

  16. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    徐峰; 文婷; 卢天健; Seffen; Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great...

  17. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    Xu Feng; Wen Ting; Lu Tianjian; Seffen Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great problem for burn patients. Thus, it is of great importance to quantify the thermal damage in skin tissue. In this paper, the available models and experimental methods for quantification of thermal damage in skin tissue are discussed.

  18. Selfies, Healthies, Usies, Felfies

    DEFF Research Database (Denmark)

    Fausing, Bent

    2014-01-01

    Spejlet hører til en af de skelsættende nyopfindelser, der udbredes i renæssancen og sætter selvet og subjektet i centrum. Det samme gør den såkaldte selfie, der siden den for alvor blev populær i løbet af sidste halvdel af 2013 har udmøntet sig i adskillige underkategorier: Healthies, Usies...

  19. Many Healthy Returns

    Centers for Disease Control (CDC) Podcasts

    2010-02-08

    International travel is usually very safe but there are things you should do to stay safe and healthy. Experts show you how to avoid problems when visiting developing nations. This includes being cautious about the food you eat and the water you drink, and to be aware of vehicles and road conditions to prevent problems.  Created: 2/8/2010 by National Center for Emerging and Zoonotic Infectious Disease (NCEZID).   Date Released: 2/8/2010.

  20. Selfies, Healthies, Usies, Felfies

    DEFF Research Database (Denmark)

    Fausing, Bent

    2014-01-01

    Spejlet hører til en af de skelsættende nyopfindelser, der udbredes i renæssancen og sætter selvet og subjektet i centrum. Det samme gør den såkaldte selfie, der siden den for alvor blev populær i løbet af sidste halvdel af 2013 har udmøntet sig i adskillige underkategorier: Healthies, Usies...

  1. Healthy Maternal Ambivalence

    OpenAIRE

    Raphael-Leff, Joan

    2010-01-01

    This paper critically reviews the psychoanalytic omission in theorizing maternal subjectivity and the subsequent idealisation of the early mother-baby bond that excludes negative maternal feelings. It suggests that painful maternal experiences of resentment, persecution and hatred remain under-explored. Perhaps, even more alarming, this exclusion compels mothers to hide conflictual and shameful feelings from professionals – and from themselves. The paper suggests that healthy maternal ambival...

  2. Stem Xylem Characterization for Vitis Drought Tolerance.

    Science.gov (United States)

    Rustioni, Laura; Ciacciulli, Angelo; Grossi, Daniele; Brancadoro, Lucio; Failla, Osvaldo

    2016-07-06

    Together with stomatal conductance and root conductivity, the stem water reserve and transport systems could be regulatory mechanisms able to participate in the regulation of the plant water status. Lianas, such as Vitis spp., minimize the trunk support role, and stems have evolved to improve their ability in water transport. In this work, stems of 10 different Vitis species were studied in relation to their expected drought tolerance using reflectance spectroscopy. Spectra were measured before (T0) and after coloration with Sudan IV dye. The T0 spectral signature showed characteristic species features. The partial least squares (PLS) regression and the self-organizing map (SOM) neural network analysis were able to predict the expected drought tolerance score; thus, reflectance spectroscopy was demonstrated to be a useful technique for drought tolerance phenotyping. These methods could be applied for the preliminary selection of new rootstocks/cultivars. Wood composition variation appeared to be correlated with the water stress susceptibility. To clarify this relationship, the attention was focused on the wood hydrophobicity. Sudan IV is a microscopy dye traditionally used to underline suberin, waxes, and, in general, hydrophobic substances. Differences between rough and colored spectra evidenced the absorption band of Sudan IV with a maximum at 539 nm. The coloration intensity was used to develop a hydrophobicity index. The obtained values were correlated with the expected drought tolerance score. Therefore, hydrophobic compounds seem to play an important role in water use efficiency, and an hydrophobic barrier in the xylem tissue appears to be a protective mechanism against water stress.

  3. Healthy Aging in China.

    Science.gov (United States)

    Smith, James P; Strauss, John; Zhao, Yaohui

    2014-12-01

    China has aged rapidly and the rate is accelerating in decades to come. We review positive and negative forces for healthy aging in China now and in the future. The most positive force is the spectacular growth in education over time especially for Chinese women, which should improve all dimensions of cognitive and physical health and eliminate vast gender disparities in healthy aging that currently exist. Other positive forces include increasing detection and treatment of disease and the availability of health insurance and health services so that diseases like hypertension and diabetes do not remain silent killers in China. Transparency is eased on the research level by publicly available data such as CHARLS, a sharp departure from prior scientific norm in China. Negative forces center on disturbing trends in personal health behaviors such as growing rates of smoking (among men) and obesity (for both genders), and pollution-,especially in urban centers. Public health campaigns and incentives are needed on all these fronts so that predictable long-term consequences of these behaviors on older age disease are not realized. There will not be a simple demographic fix to healthy aging in China as fertility rates are unlikely to rise much, while migration will likely continue to rise leaving growing numbers of elderly parents geographically separated from their adult children. Government policy will have to allow migration of elderly parents to live with their adult children while reducing the rigid connection of policy (health insurance and health services) with place of residence.

  4. A Healthy Person

    Directory of Open Access Journals (Sweden)

    Sevald Høye

    2016-05-01

    Full Text Available The purpose of this exploratory study was to investigate how nursing students in Indonesia and Scandinavia characterize a healthy person. Two hundred thirty-two nursing students from Indonesia, 50 students from Sweden, and 119 students from Norway participated by answering an open-ended question. Qualitative content analysis was used to identify patterns of health in a cultural and national context. The characteristics of a healthy person were summarized in the theme “external and inner balance,” which are intertwined because of the wholeness of self-image and appearance. The subcategories were having a strong and positive body image, feeling well and having inner harmony, following the rules of life, coping with challenges, and acting in unison with the environment. There were more similarities than differences between the Indonesian and Scandinavian nursing students’ understanding of being a healthy person. The difference is that the Scandinavian students mentioned individuality, whereas the Indonesian students referred to collective values.

  5. A Healthy Person

    Directory of Open Access Journals (Sweden)

    Sevald Høye

    2016-05-01

    Full Text Available The purpose of this exploratory study was to investigate how nursing students in Indonesia and Scandinavia characterize a healthy person. Two hundred thirty-two nursing students from Indonesia, 50 students from Sweden, and 119 students from Norway participated by answering an open-ended question. Qualitative content analysis was used to identify patterns of health in a cultural and national context. The characteristics of a healthy person were summarized in the theme “external and inner balance,” which are intertwined because of the wholeness of self-image and appearance. The subcategories were having a strong and positive body image, feeling well and having inner harmony, following the rules of life, coping with challenges, and acting in unison with the environment. There were more similarities than differences between the Indonesian and Scandinavian nursing students’ understanding of being a healthy person. The difference is that the Scandinavian students mentioned individuality, whereas the Indonesian students referred to collective values.

  6. Heat tolerance in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari

    among cultivars due to heat stress as the GD of most of them remained similar in control and stress. The second study investigated if it was possible to use detached leaves to screen for heat tolerance instead of intact plants. The previously selected 41 cultivars, known to differ in v/Fm, were used....... The main difference between the detached leaves and intact plant was the vast difference in time scale of reaction and the severity of heat stress. All the chlorophyll fluorescence parameters remained almost unaffected in control, indicating that the detachment itself did not cause the difference....... The correlation of the cultivar response in intact plant versus detached leaf was low. Overall, the result suggests that selection of cultivars by detached leaves may operate for different genetic factors than in intact plants. In the third study, the previously selected high and low groups of cultivars (from...

  7. Salt Tolerance in Soybean

    Institute of Scientific and Technical Information of China (English)

    Tsui-Hung Phang; Guihua Shao; Hon-Ming Lam

    2008-01-01

    Soybean is an Important cash crop and its productivity is significantly hampered by salt stress. High salt Imposes negative impacts on growth, nodulation, agronomy traits, seed quality and quantity, and thus reduces the yield of soybean. To cope with salt stress, soybean has developed several tolerance mechanisms, including: (I) maintenance of ion homeostasis; (ii) adjustment in response to osmotic stress; (iii) restoration of osmotic balance; and (iv) other metabolic and structural adaptations. The regulatory network for abiotic stress responses in higher plants has been studied extensively in model plants such as Arabidopsis thaliana. Some homologous components involved in salt stress responses have been identified in soybean. In this review, we tried to integrate the relevant works on soybean and proposes a working model to descdbe Its salt stress responses at the molecular level.

  8. Delay tolerant networks

    CERN Document Server

    Gao, Longxiang; Luan, Tom H

    2015-01-01

    This brief presents emerging and promising communication methods for network reliability via delay tolerant networks (DTNs). Different from traditional networks, DTNs possess unique features, such as long latency and unstable network topology. As a result, DTNs can be widely applied to critical applications, such as space communications, disaster rescue, and battlefield communications. The brief provides a complete investigation of DTNs and their current applications, from an overview to the latest development in the area. The core issue of data forward in DTNs is tackled, including the importance of social characteristics, which is an essential feature if the mobile devices are used for human communication. Security and privacy issues in DTNs are discussed, and future work is also discussed.

  9. Toleration, Synthesis or Replacement?

    DEFF Research Database (Denmark)

    Holtermann, Jakob v. H.; Madsen, Mikael Rask

    2016-01-01

    to have considerable problems keeping a clear focus on the key question: What are the implications of this empirical turn in terms of philosophy of legal science, of the social understanding of IL, and, not least, of the place of doctrinal scholarship after the alleged Wende? What is needed, we argue......, in order to answer is not yet another partisan suggestion, but rather an attempt at making intelligible both the oppositions and the possibilities of synthesis between normative and empirical approaches to law. Based on our assessment and rational reconstruction of current arguments and positions, we...... therefore outline a taxonomy consisting of the following three basic, ideal-types in terms of the epistemological understanding of the interface of law and empirical studies: toleration, synthesis and replacement. This tripartite model proves useful with a view to teasing out and better articulating...

  10. Empowering a healthy practice environment.

    Science.gov (United States)

    Kushner, Jodi; Ruffin, Tasha

    2015-03-01

    This article provides frontline nurses a tool kit so they can advocate a healthy practice environment. The healthy nurse, healthy work hours, job satisfaction, adequate sleep, power naps at work, and balancing family/work are discussed. The overweight nurse, nurse fatigue, compassion fatigue, shift work sleep disorder, and role strain are discussed as barriers to a healthy practice environment. Case reports with analysis and recommendations are discussed to overcome these barriers. Resources are presented for frontline nurses to develop a tool kit for transforming their environment to a healthy practice environment and to empower them to become healthy nurses.

  11. Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

    Science.gov (United States)

    Suárez-Zamorano, Nicolas; Fabbiano, Salvatore; Chevalier, Claire; Stojanović, Ozren; Colin, Didier J; Stevanović, Ana; Veyrat-Durebex, Christelle; Tarallo, Valentina; Rigo, Dorothée; Germain, Stéphane; Ilievska, Miroslava; Montet, Xavier; Seimbille, Yann; Hapfelmeier, Siegfried; Trajkovski, Mirko

    2015-12-01

    Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

  12. Genetics of healthy aging and longevity.

    Science.gov (United States)

    Brooks-Wilson, Angela R

    2013-12-01

    Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and

  13. Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects.

    Science.gov (United States)

    Forbes, Josephine M; Sourris, Karly C; de Courten, Maximilian P J; Dougherty, Sonia L; Chand, Vibhasha; Lyons, Jasmine G; Bertovic, David; Coughlan, Melinda T; Schlaich, Markus P; Soldatos, Georgia; Cooper, Mark E; Straznicky, Nora E; Kingwell, Bronwyn A; de Courten, Barbora

    2014-02-01

    It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

  14. Potential roles for microbial endophytes in herbicide tolerance in plants.

    Science.gov (United States)

    Tétard-Jones, Catherine; Edwards, Robert

    2016-02-01

    Herbicide tolerance in crops and weeds is considered to be monotrophic, i.e. determined by the relative susceptibility of the physiological process targeted and the plant's ability to metabolise and detoxify the agrochemical. A growing body of evidence now suggests that endophytes, microbes that inhabit plant tissues and provide a range of growth, health and defence enhancements, can contribute to other types of abiotic and biotic stress tolerance. The current evidence for herbicide tolerance being bitrophic, with both free-living and plant-associated endophytes contributing to tolerance in the host plant, has been reviewed. We propose that endophytes can directly contribute to herbicide detoxification through their ability to metabolise xenobiotics. In addition, we explore the paradigm that microbes can 'prime' resistance mechanisms in plants such that they enhance herbicide tolerance by inducing the host's stress responses to withstand the downstream toxicity caused by herbicides. This latter mechanism has the potential to contribute to the growth of non-target-site-based herbicide resistance in weeds. Microbial endophytes already contribute to herbicide detoxification in planta, and there is now significant scope to extend these interactions using synthetic biology approaches to engineer new chemical tolerance traits into crops via microbial engineering.

  15. A Multirelational Account of Toleration

    DEFF Research Database (Denmark)

    Ferretti, Maria Paola; Lægaard, Sune

    2013-01-01

    as wholes, rather than as sets of isolated relations. We explain this by showing how certain cases of toleration are multi-dimensional and how the descriptive concept of toleration might be understood intersectionally. We exemplify this by drawing on case studies of mosque controversies in Germany...

  16. Legal Quality, Inequality, and Tolerance

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    Previous findings suggest that income inequality leads to lower legal quality. This paper argues that voters' tolerance of inequality exerts an additional influence. Empirical findings suggest that inequality leads to lower legal quality due to its effect on trust while the tolerance of inequalit......, proxied by the political ideology of the median voter, exerts an independent influence....

  17. Legal Quality, Inequality, and Tolerance

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    Previous findings suggest that income inequality leads to lower legal quality. This paper argues that voters' tolerance of inequality exerts an additional influence. Empirical findings suggest that inequality leads to lower legal quality due to its effect on trust while the tolerance of inequalit......, proxied by the political ideology of the median voter, exerts an independent influence....

  18. Tissue Classification

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, David Gerald [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    The project began as a e ort to support InLight and Lumidigm. With the sale of the companies to a non-New Mexico entity, the project then focused on supporting a new company Medici Technologies. The Small Business (SB) is attempting to quantify glucose in tissue using a series of short interferometer scans of the nger. Each scan is produced from a novel presentation of the nger to the device. The intent of the project is to identify and, if possible, implement improved methods for classi cation, feature selection, and training to improve the performance of predictive algorithms used for tissue classi cation.

  19. Vitamin Supplements: Healthy or Hoax?

    Science.gov (United States)

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Vitamin Supplements: Healthy or Hoax? Updated:Jun 12,2015 Can vitamin and mineral supplements really make you healthier? Overwhelmed ...

  20. Healthy Swimming/Recreational Water

    Science.gov (United States)

    ... Now Available! Q&A with Missy Franklin: Olympic Gold Medalist and Healthy Swimming Champion New Report on ... enter your email address: Enter Email Address Submit Button What's this? Healthy Swimming Swimmers Health Benefits of ...

  1. What Makes a Healthy Pregnancy?

    Science.gov (United States)

    ... of an inherited disorder, such as sickle cell anemia, thalassemia, or Tay-Sachs disease; to screen for common genetic disorders, such as spina bifida and Down syndrome. Read More "Healthy Pregnancy" Articles What Makes a Healthy Pregnancy? / Always Meant ...

  2. Dynamics of personal development on healthy students

    Directory of Open Access Journals (Sweden)

    Kramida I.E.

    2013-04-01

    Full Text Available The aim is to study the effectiveness of different physical training for the relatively healthy students. The study involved 1004 students. The directions of development of the students' positive personal qualities. Found that the positive development of personality of students observed mostly on the first and third year than in the second. Could not find significant differences between the growth estimates of development of personality traits of students in classes in the sample program and the program specializations. Found that the rate of development of students' personality traits minor: the average growth estimates for core positive personal qualities for 3 years does not exceed 10% of the maximum possible level. Recommended in the classroom more emphasis on developing positive personality traits. It is shown that special attention should be paid to the development of emotional stability of students and their tolerance towards other people.

  3. Healthy ageing - from molecules to hormesis

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2012-01-01

    Ageing can be understood at various levels, from evolutionary and biological levels to psychological and sociological levels. At the molecular biological level ageing is characterized by the stochastic occurrence and progressive accumulation of molecular damage. Failure of homeodynamics, increased...... molecular heterogeneity, altered cellular functioning and reduced stress tolerance are the determinants of health status, probability of diseases and the duration of survival. The inefficiency and imperfection of the maintenance and repair systems underlie the biological basis of ageing. Two major issues...... life style alterations are examples of ageing interventions. A promising healthy-ageing approach is that of hormesis by strengthening the homeodynamic ability of self-maintenance through transient and repetitive mild stress-inducing hormetins. Achieving the goal of extended health-span will depend...

  4. Quantification of adipose tissue insulin sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses. Copyright © 2016 American Federation for Medical Research.

  5. Acoustic properties of healthy and reconstructed cleft lip

    Science.gov (United States)

    Thijssen, Johan M.; van Hees, Nancy J.; Weijers, Gert G.; Huyskens, Rinske W.; Nillesen, Maartje; Katsaros, Christos; de Korte, Chris L.

    2006-03-01

    The feasibility of echographic imaging of the tissues in healthy lip and in reconstructed cleft lip and estimating the dimensions and the normalized echo level of these tissues is investigated. Echographic images of the upper lip were made with commercial medical ultrasound equipment, using a linear array transducer (7-11 MHz bandwidth) and a non-contact gel coupling. Tissue dimensions were measured by means of software calipers. Echo levels were calibrated and corrected for beam characteristics, gel path and tissue attenuation by using a tissue-mimicking phantom. At central position of philtrum, mean thickness (and standard deviation) of lip loose connective tissue layer, orbicularis oris muscle and dense connective layer was 4.0 (sd 0.1) mm, 2.3 (sd 0.7) mm, 2.2 (sd 0.7) mm, respectively, in healthy lip at rest. Mean (sd) echo level of muscle and dense connective tissue layer with respect to echo level of lip loose connective tissue layer was in relaxed condition: - 19.3 (sd 0.6) dB and - 10.7 (sd 4.0) dB, respectively. Echo level of loose connective tissue layer was +25.6 (sd 4.2) dB relative to phantom echo level obtained in the focus of the transducer. Color mode echo images were calculated, after adaptive filtering of the images, which show the tissues in separate colors and highlight the details of healthy lip and reconstructed cleft lip. Quantitative assessment of thickness and echo level of various lip tissues is feasible after proper calibration of the echographic equipment. Diagnostic potentials of the developed quantitative echographic techniques for non-invasive evaluation of the outcome of cleft lip reconstruction are promising.

  6. Aluminum-Tolerant Pisolithus Ectomycorrhizas Confer Increased Growth, Mineral Nutrition, and Metal Tolerance to Eucalyptus in Acidic Mine Spoil

    Directory of Open Access Journals (Sweden)

    Louise Egerton-Warburton

    2015-01-01

    Full Text Available Ectomycorrhizal fungi (ECM may increase the tolerance of their host plants to Al toxicity by immobilizing Al in fungal tissues and/or improving plant mineral nutrition. Although these benefits have been demonstrated in in vitro (pure culture or short-term nutrient solution (hydroponic experiments, fewer studies have examined these benefits in the field. This study examined the growth, mineral nutrition, and Al levels in two Eucalyptus species inoculated with three Pisolithus ecotypes that varied in Al tolerance (in vitro and grown in mine spoil in the greenhouse and field. All three ecotypes of Pisolithus improved Eucalyptus growth and increased host plant tolerance to Al in comparison to noninoculated plants. However, large variations in plant growth and mineral nutrition were detected among the Pisolithus-inoculated plants; these differences were largely explained by the functional properties of the Pisolithus inoculum. Seedlings inoculated with the most Al-tolerant Pisolithus inoculum showed significantly higher levels of N, P, Ca, Mg, and K and lower levels of Al than seedlings inoculated with Al-sensitive ecotypes of Pisolithus. These findings indicate an agreement between the fungal tolerance to Al in vitro and performance in symbiosis, indicating that both ECM-mediated mineral nutrient acquisition and Al accumulation are important in increasing the host plant Al tolerance.

  7. [Food additives and healthiness].

    Science.gov (United States)

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  8. Healthy eating at schools

    DEFF Research Database (Denmark)

    Sabinsky, Marianne

    . The present PhD thesis is based on evaluation of the dietary effect of this project. There is room for improvement of the dietary habits of Danish children. Dietary habits are influenced by multiple factors across different contexts. The school setting is known as a suitable arena for promotion of healthy...... into account the multiple factors and environments which affect the dietary habits of children. The focus of such an intervention could be implementation of a sustainable school food programme. Another focus could be improvement of the packed lunches brought from home with the purpose to contribute...

  9. Healthy Smile for Your Baby

    Science.gov (United States)

    ... your baby’s gums or brush your baby’s teeth, give your baby healthy foods, and take your baby to the dentist by the time ... they have teeth, you should clean their gums. Give your baby a healthy start! Here are tips ... healthy. Take Care of Your Baby’s Mouth m Clean your ...

  10. From immunosuppression to tolerance.

    Science.gov (United States)

    Adams, David H; Sanchez-Fueyo, Alberto; Samuel, Didier

    2015-04-01

    The past three decades have seen liver transplantation becoming a major therapeutic approach in the management of end-stage liver diseases. This is due to the dramatic improvement in survival after liver transplantation as a consequence of the improvement of surgical and anaesthetic techniques, of post-transplant medico-surgical management and of prevention of disease recurrence and other post-transplant complications. Improved use of post-transplant immunosuppression to prevent acute and chronic rejection is a major factor in these improved results. The liver has been shown to be more tolerogenic than other organs, and matching of donor and recipients is mainly limited to ABO blood group compatibility. However, long-term immunosuppression is required to avoid severe acute and chronic rejection and graft loss. With the current immunosuppression protocols, the risk of acute rejection requiring additional therapy is 10-40% and the risk of chronic rejection is below 5%. However, the development of histological lesions in the graft in long-term survivors suggest atypical forms of graft rejection may develop as a consequence of under-immunosuppression. The backbone of immunosuppression remains calcineurin inhibitors (CNI) mostly in association with steroids in the short-term and mycophenolate mofetil or mTOR inhibitors (everolimus). The occurrence of post-transplant complications related to the immunosuppressive therapy has led to the development of new protocols aimed at protecting renal function and preventing the development of de novo cancer and of dysmetabolic syndrome. However, there is no new class of immunosuppressive drugs in the pipeline able to replace current protocols in the near future. The aim of a full immune tolerance of the graft is rarely achieved since only 20% of selected patients can be weaned successfully off immunosuppression. In the future, immunosuppression will probably be more case oriented aiming to protect the graft from rejection and at

  11. General tolerances -- Part 2: Geometrical tolerances for features without individual tolerance indications

    CERN Document Server

    International Organization for Standardization. Geneva

    1989-01-01

    This part is intended to simplify drawing indications and specifies general tolerances in three tolerance classes. It mainly applies to features which are produced by removal of material. It contains tour tables and an informative annex A with regard to concepts behind general tolerancing of dimensions, as well as an informative annex B with further information.

  12. A CAD MODEL FOR FUZZY CONCURRENT TOLERANCE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Research situation of concurrent tolerance design has been analyzed. As fuzzy factors are objective and unavoidable in concurrent tolerance design, fuzzy optimization theory is applied in the design. A new mathematical model of concurrent tolerance design is constructed.

  13. Manufacturing tolerant topology optimization

    Institute of Scientific and Technical Information of China (English)

    Ole Sigmund

    2009-01-01

    In this paper we present an extension of the topology optimization method to include uncertainties during the fabrication of macro, micro and nano structures. More specifically, we consider devices that are manufactured using processes which may result in (uniformly) too thin (eroded)or too thick (dilated) structures compared to the intended topology. Examples are MEMS devices manufactured using etching processes, nano-devices manufactured using e-beam lithography or laser micro-machining and macro structures manufactured using milling processes. In the suggested robust topology optimization approach, under- and over-etching is modelled by image processing-based "erode" and "dilate" operators and the optimization problem is formulated as a worst case design problem. Applications of the method to the design of macro structures for minimum compliance and micro compliant mechanisms show that the method provides manufacturing tolerant designs with little decrease in performance. As a positive side effect the robust design formulation also eliminates the longstanding problem of one-node connected hinges in compliant mechanism design using topology optimization.

  14. Chitin Scaffolds in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Tetsuya Furuike

    2011-03-01

    Full Text Available Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.

  15. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2011-01-01

    Use Tolerance Analysis Techniques to Avoid Design, Quality, and Manufacturing Problems Before They Happen Often overlooked and misunderstood, tolerance analysis is a critical part of improving products and their design processes. Because all manufactured products are subject to variation, it is crucial that designers predict and understand how these changes can affect form, fit, and function of parts and assemblies--and then communicate their findings effectively. Written by one of the developers of ASME Y14.5 and other geometric dimension and tolerancing (GD&T) standards, Mechanical Tolerance

  16. Tolerance to noninherited maternal antigens, reproductive microchimerism and regulatory T cell memory: 60 years after ‘Evidence for actively acquired tolerance to Rh antigens’

    Science.gov (United States)

    Kinder, Jeremy M.; Jiang, Tony T.; Ertelt, James M.; Xin, Lijun; Strong, Beverly S.; Shaaban, Aimen F.; Way, Sing Sing

    2015-01-01

    ABSTRACT Compulsory exposure to genetically foreign maternal tissue imprints in offspring sustained tolerance to noninherited maternal antigens (NIMA). Immunological tolerance to NIMA was first described by Dr. Ray D. Owen for women genetically negative for erythrocyte rhesus (Rh) antigen with reduced sensitization from developmental Rh exposure by their mothers. Extending this analysis to HLA haplotypes has uncovered the exciting potential for therapeutically exploiting NIMA-specific tolerance naturally engrained in mammalian reproduction for improved clinical outcomes after allogeneic transplantation. Herein, we summarize emerging scientific concepts stemming from tolerance to NIMA that includes postnatal maintenance of microchimeric maternal origin cells in offspring, expanded accumulation of immune suppressive regulatory T cells with NIMA-specificity, along with teleological benefits and immunological consequences of NIMA-specific tolerance conserved across mammalian species. PMID:26517600

  17. Autoimmune regulator and self-tolerance - molecular and clinical aspects.

    Science.gov (United States)

    Abramson, Jakub; Husebye, Eystein S

    2016-05-01

    The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator (AIRE), the causative gene in autoimmune polyendocrine syndrome type-1 (APS-1), is crucial for the establishment of self-tolerance in the thymus by promoting promiscuous expression of a wide array of tissue-restricted self-antigens. This step is critical for elimination of high-affinity self-reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3(+) T-regulatory (Treg ) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self-tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes.

  18. Improved adipose tissue metabolism after 5-year growth hormone replacement therapy in growth hormone deficient adults: The role of zinc-α2-glycoprotein.

    Science.gov (United States)

    Balaž, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Vlcek, Miroslav; Surova, Martina; Krumpolec, Patrik; Vanuga, Peter; Gašperíková, Daniela; Klimeš, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2015-01-01

    Growth hormone (GH) supplementation therapy to adults with GH deficiency has beneficial effects on adipose tissue lipid metabolism, improving thus adipocyte functional morphology and insulin sensitivity. However, molecular nature of these effects remains unclear. We therefore tested the hypothesis that lipid-mobilizing adipokine zinc-α2-glycoprotein is causally linked to GH effects on adipose tissue lipid metabolism. Seventeen patients with severe GH deficiency examined before and after the 5-year GH replacement therapy were compared with age-, gender- and BMI-matched healthy controls. Euglycemic hyperinsulinemic clamp was used to assess whole-body and adipose tissue-specific insulin sensitivity. Glucose tolerance was determined by oGTT, visceral and subcutaneous abdominal adiposity by MRI, adipocyte size morphometrically after collagenase digestion, lipid accumulation and release was studied in differentiated human primary adipocytes in association with GH treatment and zinc-α2-glycoprotein gene silencing. Five-year GH replacement therapy improved glucose tolerance, adipose tissue insulin sensitivity and reduced adipocyte size without affecting adiposity and whole-body insulin sensitivity. Adipose tissue zinc-α2-glycoprotein expression was positively associated with whole-body and adipose tissue insulin sensitivity and negatively with adipocyte size. GH treatment to adipocytes in vitro increased zinc-α2-glycoprotein expression (>50%) and was paralleled by enhanced lipolysis and decreased triglyceride accumulation (>35%). Moreover, GH treatment improved antilipolytic action of insulin in cultured adipocytes. Most importantly, silencing zinc-α2-glycoprotein eliminated all of the GH effects on adipocyte lipid metabolism. Effects of 5-year GH supplementation therapy on adipose tissue lipid metabolism and insulin sensitivity are associated with zinc-α2-glycoprotein. Presence of this adipokine is required for the GH action on adipocyte lipid metabolism in vitro.

  19. Breach of autoreactive B cell tolerance by post-translationally modified proteins.

    Science.gov (United States)

    Dekkers, Jacqueline S; Verheul, Marije K; Stoop, Jeroen N; Liu, Bisheng; Ioan-Facsinay, Andreea; van Veelen, Peter A; de Ru, Arnoud H; Janssen, George M C; Hegen, Martin; Rapecki, Steve; Huizinga, Tom W J; Trouw, Leendert A; Toes, René E M

    2017-08-01

    Over 50% of patients with rheumatoid arthritis (RA) harbour a variety of anti-modified protein antibodies (AMPA) against different post-translationally modified (PTM) proteins, including anti-carbamylated protein (anti-CarP) antibodies. At present, it is unknown how AMPA are generated and how autoreactive B cell responses against PTM proteins are induced. Here we studied whether PTM foreign antigens can breach B cell tolerance towards PTM self-proteins. Serum reactivity towards five carbamylated proteins was determined for 160 patients with RA and 40 healthy individuals. Antibody cross-reactivity was studied by inhibition experiments. Mass spectrometry was performed to identify carbamylated self-proteins in human rheumatic joint tissue. Mice were immunised with carbamylated or non-modified (auto)antigens and analysed for autoantibody responses. We show that anti-CarP antibodies in RA are highly cross-reactive towards multiple carbamylated proteins, including modified self-proteins and modified non-self-proteins. Studies in mice show that anti-CarP antibody responses recognising carbamylated self-proteins are induced by immunisation with carbamylated self-proteins and by immunisation with carbamylated proteins of non-self-origin. Similar to the data observed with sera from patients with RA, the murine anti-CarP antibody response was, both at the monoclonal level and the polyclonal level, highly cross-reactive towards multiple carbamylated proteins, including carbamylated self-proteins. Self-reactive AMPA responses can be induced by exposure to foreign proteins containing PTM. These data show how autoreactive B cell responses against PTM self-proteins can be induced by exposure to PTM foreign proteins and provide new insights on the breach of autoreactive B cell tolerance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Towards healthy cities.

    Science.gov (United States)

    Satterthwaite, D

    1996-01-01

    Cities contain many of the world's most unhealthy living environments. They are considered ecologically unsustainable because of high consumption and waste levels, attributed to high population density. However, well planned and managed cities can combine high living standards with remarkably low levels of energy consumption, resource use and wastes. The concentration of people and production creates many more possibilities of collecting and recycling wastes and for walking, bicycling and a high quality public transport. This potential for providing healthy, stimulating and valued places to live and work for all age groups could be achieved with good governance. In any city, this approach means encouragement and support from all levels of government for a great range of investments of capital, expertise and time by individuals, households, communities, voluntary organizations and nongovernmental organizations, as well as private enterprises. Moreover, this means managing competing claims and finding common ground between enterprises, trade unions and residents about what should be done to make the city healthier.

  1. Healthy and productive workers

    DEFF Research Database (Denmark)

    Ammendolia, Carlo; Côté, Pierre; Cancelliere, Carol

    2016-01-01

    and stakeholder experience. This was then systematically operationalized into a program using discussion groups and consensus among experts and stakeholders. RESULTS: The top health problem impacting our workplace partner was mental health. Depression and stress were the first and second highest cause...... of productivity loss respectively. A multi-pronged program with detailed action steps was developed and directed at key stakeholders and health conditions. For mental health, regular sharing focus groups, social networking, monthly personal stories from leadership using webinars and multi-media communications......, expert-led workshops, lunch and learn sessions and manager and employee training were part of a comprehensive program. Comprehensive, specific and multi-pronged strategies were developed and aimed at encouraging healthy behaviours that impact presenteeism such as regular exercise, proper nutrition...

  2. Accident tolerant fuel analysis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Curtis [Idaho National Laboratory; Chichester, Heather [Idaho National Laboratory; Johns, Jesse [Texas A& M University; Teague, Melissa [Idaho National Laboratory; Tonks, Michael Idaho National Laboratory; Youngblood, Robert [Idaho National Laboratory

    2014-09-01

    Safety is central to the design, licensing, operation, and economics of Nuclear Power Plants (NPPs). Consequently, the ability to better characterize and quantify safety margin holds the key to improved decision making about light water reactor design, operation, and plant life extension. A systematic approach to characterization of safety margins and the subsequent margins management options represents a vital input to the licensee and regulatory analysis and decision making that will be involved. The purpose of the Risk Informed Safety Margin Characterization (RISMC) Pathway research and development (R&D) is to support plant decisions for risk-informed margins management by improving economics and reliability, and sustaining safety, of current NPPs. Goals of the RISMC Pathway are twofold: (1) Develop and demonstrate a risk-assessment method coupled to safety margin quantification that can be used by NPP decision makers as part of their margin recovery strategies. (2) Create an advanced ''RISMC toolkit'' that enables more accurate representation of NPP safety margin. In order to carry out the R&D needed for the Pathway, the Idaho National Laboratory is performing a series of case studies that will explore methods- and tools-development issues, in addition to being of current interest in their own right. One such study is a comparative analysis of safety margins of plants using different fuel cladding types: specifically, a comparison between current-technology Zircaloy cladding and a notional ''accident-tolerant'' (e.g., SiC-based) cladding. The present report begins the process of applying capabilities that are still under development to the problem of assessing new fuel designs. The approach and lessons learned from this case study will be included in future Technical Basis Guides produced by the RISMC Pathway. These guides will be the mechanism for developing the specifications for RISMC tools and for defining how plant

  3. Down Syndrome in Adults: Staying Healthy

    Science.gov (United States)

    ... Shortfall Questionnaire Home Prevention and Wellness Staying Healthy Down Syndrome in Adults: Staying Healthy Down Syndrome in Adults: Staying Healthy Family HealthPrevention and WellnessStaying ...

  4. Extraintestinal heterotopic gastric tissue simulating acute appendicitis

    Institute of Scientific and Technical Information of China (English)

    Elizabeth Bender; Steven P Schmidt

    2008-01-01

    We describe the case of a 68-year-old otherwise healthy male who presented to our emergency room with signs and symptoms of acute appendicitis. Exploratory surgery revealed a normal appendix. Further examination revealed an enlarged lymph node-like mass of tissue near the appendix, in the ileocecal mesentery. This mass was removed and was found to be inflamed heterotopic gastric tissue. Although reports of heterotopic gastric tissue in the literature are common, we believe that this case represents the first report of inflamed heterotopic gastric tissue simulating appendicitis.

  5. Wheat seedlings as a model to understand desiccation tolerance and sensitivity.

    Science.gov (United States)

    Farrant, Jill M.; Bailly, Christophe; Leymarie, Juliette; Hamman, Brigitte; Côme, Daniel; Corbineau, Françoise

    2004-04-01

    The coleoptiles of wheat (Triticum aestivum L.) seedlings of cultivar Trémie are desiccation tolerant when 3 days old, although the roots are not. Cutting some of the coleoptiles open prior to dehydration rapidly increased the drying rate. This rendered the coleoptiles sensitive to desiccation, providing a useful model with which to study desiccation tolerance. Both sensitive and tolerant seedlings were dehydrated to 0.3 g H(2)O g(-1) dry mass (g.g) and thereafter rehydrated. Sensitive tissues accr- ued the lipid peroxidation products H(2)O(2)and MDA, and substantial subcellular damage was evident in dry tissues. H(2)O(2) and MDA accumulated slightly only in dry tolerant coleoptiles and no subcellular damage was evident. The activity of antioxidant enzymes glutathione reductase (EC1.6.2.4), superoxide dismutase (EC 1.14.1.1) and catalase (EC 1.11.1.6) increased on drying in both tolerant and sensitive tissues, but were sustained on rehydration in only the tolerant tissues. It is proposed that free radical damage sustained during rapid drying exceeded the ameliorating capacity of antioxidant systems, allowed accrual of lethal subcellular damage. Slow drying enabled sufficient detoxification by antioxidants to minimize damage and allow tolerance to drying. Three LEA- (p11 and Asp 52) and dehydrin- (XV8) like proteins were detected by western blots in tolerant coleoptiles dried to 3.0 g.g and below. Only one (Asp 52) was induced at low water content in rapidly dried sensitive coleoptiles. None were present in root tissues. XV8 RNA (northern analyses) was induced on drying only in tolerant coleoptiles and correlated with protein expression. These stress-putative protein protectants (and XV8 transcripts) appear to be down-regulated during germination but wheat seedlings temporarily retain the ability to reproduce them if drying is slow. Sucrose accumulation during dehydration was similar for both sensitive and tolerant tissues, suggesting that this sugar has little

  6. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  7. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  8. When Should Sects be Tolerated?

    DEFF Research Database (Denmark)

    Hvithamar, Annika

    2009-01-01

    Jehovas vidners kontroverser med majoritetssamfundet gør dem til et godt test-case for tolerance. I artiklen bruges udviklingen af bevægelsens syn på blodstransfusioner til at diskutere, hvordan institutionaliseringen af en minoritetsbevægelse får kontroversernes styrke til at mindskes, men også...... hvordan udviklingen af tolerance er en gensidig proces, hvor minoritetsreligionen og majoritetssamfundet påvirker hinanden....

  9. Women’s G Tolerance

    Science.gov (United States)

    1986-08-01

    for the groups matched by age (70 pairs), weight sickness, uncomfortable feelings of distension in arms (26 pairs), and act~vity status (84 pairs...mass-spring-damper) s ,stem Straining G tolerance, being dpendent on skeletal having a resonant frequency above about I Hz. As muscular strength and...of the women’s G tolerance stud\\ scclic variations in muscular strength and endurance. was below 0.1 Hz (11), the production of any significant

  10. Fault-tolerant rotary actuator

    Science.gov (United States)

    Tesar, Delbert

    2006-10-17

    A fault-tolerant actuator module, in a single containment shell, containing two actuator subsystems that are either asymmetrically or symmetrically laid out is provided. Fault tolerance in the actuators of the present invention is achieved by the employment of dual sets of equal resources. Dual resources are integrated into single modules, with each having the external appearance and functionality of a single set of resources.

  11. Repair of lower extremity soft tissue defect with free musculo-cutaneous flaps bridging with healthy contralateral posterior tibial vessel%游离肌皮瓣桥接胫后血管修复对侧下肢软组织缺损

    Institute of Scientific and Technical Information of China (English)

    夏成德; 狄海萍; 薛继东; 赵耀华; 李晓亮; 李强; 牛希华; 李永林; 连鸿凯

    2015-01-01

    Objective To observe the clinical effects of free musculo-cutaneous flap bridging with contralateral posterior tibial vessel on repair of lower extremity soft tissue defect.Methods From February 2006 to June 2013,10 patients with soft tissue defect on lower shank and foot were included.The posterior tibial vessel on healthy lower extremity was chosen as recipient vessel and anastomosed with free latissimus dorsi musculo-cutaneous flap,or free latissimus dorsi musculo-cutaneous flap combined with thoracic-umbilical skin flap or anterolateral femoral musculo-cutaneous flap.The retrograde bridged flap was transposed to repair defect on contralateral lower shank and foot.The wound area ranged from 40 cm × 21 cm to 22 cm×15 cm,with flap size from 48 cm×26 cm to 25 cm×18 cm.Meanwhile the defects on donor sites were covered with skin graft and both lower extremities were fixed with kirschner wires at middle tibia and calcaneus.The kirschner wires were removed at 4 weeks and pedicles were cut off 5 ~ 8 weeks postoperatively.Six patients received posterior tibial vessel reanastomosis at the same time of pedicle cutting.Results All the 10 flaps survived and 3 patients received thinning of flaps due to excessive thickness.During the follow-up period of 3 months to 2 years follow up,the ambulatory function of injured legs recovered gradually with satisfactory appearance.The reanastomosed posterior tibial vessel on the healthy side was recovered.Conclusions Appropriate bridged musculo-cutaneous flaps is suitable for extensive soft tissue defect of lower shank and foot.It is a safe and effective method for limb salvage.%目的 观察游离肌皮瓣与健肢胫后血管桥接修复对侧下肢软组织缺损的临床效果.方法 2006年2月至2013年6月,对10例小腿下段及足部软组织缺损患者,应用健肢胫后血管与游离背阔肌肌皮瓣、背阔肌肌皮瓣联合胸脐皮瓣、股前外侧肌肌皮瓣的血管吻合,形成以健肢

  12. Tolerance to the carbamate insecticide propoxur.

    Science.gov (United States)

    Costa, L G; Hand, H; Schwab, B W; Murphy, S D

    1981-01-01

    Male mice were given the carbamate insecticide propoxur (2-isopropoxy phenyl methylcarbamate; Baygon) in the drinking water at weekly increasing concentrations (from 50 to 2000 ppm), for a period of 6 weeks. At the end of the treatment the LD50 for propoxur was significantly higher in the treated animals as compared with controls. Propoxur-treated animals were also resistant to the hypothermic effect of an acute administration of the same compound. Groups of mice were challenged with the cholinergic agonist carbachol at intervals during the drinking water dosing and at its end. No differences in sensitivity to carbachol acute toxicity were found between control and treated animals. Propoxur-tolerant animals were also not resistant to the hypothermic effect of oxotremorine, another cholinergic agonist. [3H]Quinuclidinyl benzilate ([3H]QNB) binding (a measure of muscarinic receptor density and affinity) in forebrain, hindbrain and ileum never differed in control and treated mice. The possibility that repeated administrations of propoxur induced increased metabolic inactivation was tested by measuring hexobarbital sleeping time and carboxylesterase activity in treated and control mice. No changes in tissue carboxylesterase activities occurred but hexobarbital sleeping time was significantly reduced in propoxur treated animals suggesting an induction of hepatic microsomal enzymes. These results suggest that tolerance to propoxur is not mediated by a decrease of cholinergic receptors, as reported for other acetylcholinesterase inhibitors, but possibly by an enhancement of its metabolism.

  13. Enhancement of reproductive heat tolerance in plants.

    Directory of Open Access Journals (Sweden)

    John J Burke

    Full Text Available Comparison of average crop yields with reported record yields has shown that major crops exhibit annual average yields three- to seven-fold lower than record yields because of unfavorable environments. The current study investigated the enhancement of pollen heat tolerance through expressing an Arabidopsis thaliana heat shock protein 101 (AtHSP101 that is not normally expressed in pollen but reported to play a crucial role in vegetative thermotolerance. The AtHSP101 construct under the control of the constitutive ocs/mas 'superpromoter' was transformed into cotton Coker 312 and tobacco SRI lines via Agrobacterium mediated transformation. Thermotolerance of pollen was evaluated by in vitro pollen germination studies. Comparing with those of wild type and transgenic null lines, pollen from AtHSP101 transgenic tobacco and cotton lines exhibited significantly higher germination rate and much greater pollen tube elongation under elevated temperatures or after a heat exposure. In addition, significant increases in boll set and seed numbers were also observed in transgenic cotton lines exposed to elevated day and night temperatures in both greenhouse and field studies. The results of this study suggest that enhancing heat tolerance of reproductive tissues in plant holds promise in the development of crops with improved yield production and yield sustainability in unfavorable environments.

  14. Heavy metal pollutant tolerance of Azolla pinnata

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, A.; Jana, S.

    1986-01-01

    The effects of Hg, As, Pb, Cu, Cd, and Cr (1,2 and 5 mg L/sup -1/ each) on Azolla pinnata R. Br. were analyzed. The treatments (2 and 5 mg L/sup -1/) of the heavy metal pollutants decreased Hill activity, chlorophyll, protein and dry wt, and increased tissue permeability over control values. The effects were most pronounced with the treatment of 5 mg L/sup -1/. The harmful effects of the metals were, in general, found by the treatments in the order: Cd > Hg > Cu > As > Pb > Cr. There was no significant change in these parameters at 1 mg L/sup -1/ of the metals over control. Thus Azolla pinnata shows tolerance to the heavy metals tested up to 1 mg L/sup -1/ each.

  15. Molecular mechanisms of desiccation tolerance in resurrection plants.

    Science.gov (United States)

    Gechev, Tsanko S; Dinakar, Challabathula; Benina, Maria; Toneva, Valentina; Bartels, Dorothea

    2012-10-01

    Resurrection plants are a small but diverse group of land plants characterized by their tolerance to extreme drought or desiccation. They have the unique ability to survive months to years without water, lose most of the free water in their vegetative tissues, fall into anabiosis, and, upon rewatering, quickly regain normal activity. Thus, they are fundamentally different from other drought-surviving plants such as succulents or ephemerals, which cope with drought by maintaining higher steady state water potential or via a short life cycle, respectively. This review describes the unique physiological and molecular adaptations of resurrection plants enabling them to withstand long periods of desiccation. The recent transcriptome analysis of Craterostigma plantagineum and Haberlea rhodopensis under drought, desiccation, and subsequent rehydration revealed common genetic pathways with other desiccation-tolerant species as well as unique genes that might contribute to the outstanding desiccation tolerance of the two resurrection species. While some of the molecular responses appear to be common for both drought stress and desiccation, resurrection plants also possess genes that are highly induced or repressed during desiccation with no apparent sequence homologies to genes of other species. Thus, resurrection plants are potential sources for gene discovery. Further proteome and metabolome analyses of the resurrection plants contributed to a better understanding of molecular mechanisms that are involved in surviving severe water loss. Understanding the cellular mechanisms of desiccation tolerance in this unique group of plants may enable future molecular improvement of drought tolerance in crop plants.

  16. Tilt-table testing as a predictor of + GZ tolerance

    Directory of Open Access Journals (Sweden)

    Zawadzka-Bartczak E

    2005-11-01

    Full Text Available BACKGROUND: G-tolerance assessment is an essential element of both military pilot and pilot candidate evaluation. AIMS: Attempt at prediction of individual relaxed + Gz tolerance on the basis of head-up tilt (HUT testing. SETTINGS AND DESIGN: In two stages, 20 healthy men at the mean age 21.5 years took part in this study. The first stage, a 45 min, HUT test was performed using the Westminster protocol. During the second stage each underwent a centrifuge evaluation in response to gradual onset rate profiles. METHODS AND MATERIAL: In each subject, heart rate (HR and blood pressure (BP before and at 2, 15 and 45 min of the tilt-test were recorded. The gravity-load centrifuge (GOR studies were carried out [following the standard GOR programme, at 0.1 G/s rate of gravity load increase until the gravity load tolerance limit (loss of peripheral vision was reached]. STATISTICAL ANALYSIS USED: Relationships between variables were explored using Kendall′s tau-B correlation coefficient. The critical P-level was one-tailed 0.05. RESULTS: In four of 20 subjects (20%, vasovagal syncope occurred during the tilt test. G-level tolerance of this group (of +Gz accelerations lay in the range from +4 to +8.1 Gz, (+5.72 ? 0.86 Gz average and was comparable to the group without syncope. Loss of consciousness did not occur in any subjects during the centrifuge test. No statistically significant correlation was observed between HR and BP during tilt test and tolerance to +Gz accelerations. CONCLUSIONS: The result of tilt testing, carried out according to the Westminster protocol, was not useful in predicting individual tolerance to +Gz gravity loads.

  17. Studies on peripheral tolerance in Aire deficient mice

    OpenAIRE

    Lindmark, Evelina

    2013-01-01

    Autoimmune diseases such as diabetes mellitus and multiple sclerosis are increasing today, but the mechanism behind these diseases remains largely unknown. Autoimmunity arise when the immune system of an individual start to attack its own organs and tissues. Immune cells go through a selection in central and peripheral organs where they are taught to be non-reactive to self structures, a process referred to as tolerance. In this thesis we have investigated the function of ...

  18. The submergence tolerance regulator SUB1A mediates crosstalk between submergence and drought tolerance in rice.

    Science.gov (United States)

    Fukao, Takeshi; Yeung, Elaine; Bailey-Serres, Julia

    2011-01-01

    Submergence and drought are major constraints to rice (Oryza sativa) production in rain-fed farmlands, both of which can occur sequentially during a single crop cycle. SUB1A, an ERF transcription factor found in limited rice accessions, dampens ethylene production and gibberellic acid responsiveness during submergence, economizing carbohydrate reserves and significantly prolonging endurance. Here, we evaluated the functional role of SUB1A in acclimation to dehydration. Comparative analysis of genotypes with and without SUB1A revealed that SUB1A enhanced recovery from drought at the vegetative stage through reduction of leaf water loss and lipid peroxidation and increased expression of genes associated with acclimation to dehydration. Overexpression of SUB1A augmented ABA responsiveness, thereby activating stress-inducible gene expression. Paradoxically, vegetative tissue undergoes dehydration upon desubmergence even though the soil contains sufficient water, indicating that leaf desiccation occurs in the natural progression of a flooding event. Desubmergence caused the upregulation of gene transcripts associated with acclimation to dehydration, with higher induction in SUB1A genotypes. SUB1A also restrained accumulation of reactive oxygen species (ROS) in aerial tissue during drought and desubmergence. Consistently, SUB1A increased the abundance of transcripts encoding ROS scavenging enzymes, resulting in enhanced tolerance to oxidative stress. Therefore, in addition to providing robust submergence tolerance, SUB1A improves survival of rapid dehydration following desubmergence and water deficit during drought.

  19. Terahertz pulsed imaging of freshly excised human colonic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Caroline B; Gibson, Adam P [Department of Medical Physics and Bioengineering, University College London, London, WC1E 6BT (United Kingdom); Fitzgerald, Anthony; Wallace, Vincent P [School of Physics, University of Western Australia, Crawley 6009 (Australia); Reese, George; Tekkis, Paris [Division of Surgery, Chelsea and Westminster Campus, Imperial College London, London (United Kingdom); Goldin, Robert [Centre for Pathology, Imperial College London, St Mary' s Campus, London (United Kingdom); O' Kelly, P S [TeraView Ltd, Platinum Building, St John' s Innovation Park, Cowley Road, Cambridge, CB4 0WS (United Kingdom); Pickwell-MacPherson, Emma, E-mail: c.reid@medphys.ucl.ac.uk [Department of Electronic Engineering, Chinese University of Hong Kong, Shatin, NT (Hong Kong)

    2011-07-21

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  20. Proteomic study of low-temperature responses in strawberry cultivars (Fragaria x ananassa) that differ in cold tolerance.

    Science.gov (United States)

    Koehler, Gage; Wilson, Robert C; Goodpaster, John V; Sønsteby, Anita; Lai, Xianyin; Witzmann, Frank A; You, Jin-Sam; Rohloff, Jens; Randall, Stephen K; Alsheikh, Muath

    2012-08-01

    To gain insight into the molecular basis contributing to overwintering hardiness, a comprehensive proteomic analysis comparing crowns of octoploid strawberry (Fragaria × ananassa) cultivars that differ in freezing tolerance was conducted. Four cultivars were examined for freeze tolerance and the most cold-tolerant cultivar ('Jonsok') and least-tolerant cultivar ('Frida') were compared with a goal to reveal how freezing tolerance is achieved in this distinctive overwintering structure and to identify potential cold-tolerance-associated biomarkers. Supported by univariate and multivariate analysis, a total of 63 spots from two-dimensional electrophoresis analysis and 135 proteins from label-free quantitative proteomics were identified as significantly differentially expressed in crown tissue from the two strawberry cultivars exposed to 0-, 2-, and 42-d cold treatment. Proteins identified as cold-tolerance-associated included molecular chaperones, antioxidants/detoxifying enzymes, metabolic enzymes, pathogenesis-related proteins, and flavonoid pathway proteins. A number of proteins were newly identified as associated with cold tolerance. Distinctive mechanisms for cold tolerance were characterized for two cultivars. In particular, the 'Frida' cold response emphasized proteins specific to flavonoid biosynthesis, while the more freezing-tolerant 'Jonsok' had a more comprehensive suite of known stress-responsive proteins including those involved in antioxidation, detoxification, and disease resistance. The molecular basis for 'Jonsok'-enhanced cold tolerance can be explained by the constitutive level of a number of proteins that provide a physiological stress-tolerant poise.