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Sample records for twelve healthy human

  1. Enantioselective HPLC-DAD method for the determination of etodolac enantiomers in tablets, human plasma and application to comparative pharmacokinetic study of both enantiomers after a single oral dose to twelve healthy volunteers.

    Science.gov (United States)

    Hewala, Ismail I; Moneeb, Marwa S; Elmongy, Hatem A; Wahbi, Abdel-Aziz M

    2014-12-01

    An enantioselective high performance liquid chromatographic method with diode array detection (HPLC-DAD) was developed and validated for the determination of etodolac enantiomers in tablets and human plasma. Enantiomeric separation was achieved on a Kromasil Cellucoat chiral column (250 mm × 4.6mm i.d., 5 µm particle size) using a mobile phase consisting of hexane: isopropanol: triflouroacetic acid (90:10:0.1 v/v/v) at a flow rate of 1.0 mL min(-1). The chromatographic system enables the separation of the two enantiomers and the internal standard within a cycle time of 8 min. The resolution between the two enantiomers was 4.25 and the resolution between each enantiomer and the internal standard was more than 2.0. Detection was carried out at 274 nm, and the purity assessment was performed using a photodiode array detector. Solid phase extraction technique using C-18 cartridge was applied to extract the analytes from the plasma samples, and the percentage recovery was more than 95% for the lower quantification limit. The method has been validated with respect to selectivity, linearity, accuracy and precision, robustness, limit of detection and limit of quantification. The validation acceptance criteria were met in all cases. The linearity range for the determination of each enantiomer in human plasma was 0.4-30.0 µg mL(-1) and the limits of quantification of R-etodolac and S-etodolac were 0.20 and 0.19 µg mL(-1), respectively. The validated method was successfully applied to the determination of etodolac enantiomers in tablets and to a comparative pharmacokinetic study of the two enantiomers after the administration of 300 mg single oral dose etodolac racemate tablets to twelve healthy volunteers.

  2. Human Evolution in Science Textbooks from Twelve Different Countries

    Science.gov (United States)

    Quessada, Marie-Pierre; Clement, Pierre; Oerke, Britta; Valente, Adriana

    2008-01-01

    What kinds of images of human beings illustrate human evolution in school textbooks? A comparison between the textbooks of eighteen different countries (twelve European countries and six non-European countries) was attempted. In six countries (Algeria, Malta, Morocco, Mozambique, Portugal, and Tunisia), we did not find any chapter on the topic of…

  3. "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…

  4. "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…

  5. 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

  6. 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

  7. Stress and memory in humans: twelve years of progress?

    Science.gov (United States)

    Wolf, Oliver T

    2009-10-13

    Stress leads to an enhanced activity of the hypothalamus-pituitary adrenal (HPA) axis resulting in an increased release of glucocorticoids from the adrenal cortex. These hormones influence target systems in the periphery as well as in the brain. The present review paper describes the impact of the human stress hormone cortisol on episodic long-term memory. Starting out with our early observation that stress as well as cortisol treatment impaired declarative memory, experiments by the author are described, which result in an enhanced understanding of how cortisol influences memory. The main conclusions are that stress or cortisol treatment temporarily blocks memory retrieval. The effect is stronger for emotional arousing material independent of its valence. In addition cortisol only influences memory when a certain amount of testing induced arousal occurs. A functional magnetic resonance imaging (fMRI) study suggests that the neuronal correlate of the cortisol induced retrieval blockade is a reduced activity of the hippocampus. In contrast to the effects on retrieval cortisol enhances memory consolidation. Again this effect is often stronger for emotionally arousing material and sometimes occurs at the cost of memory for neutral material. A fMRI study revealed that higher cortisol levels were associated with a stronger amygdala response to emotional stimuli. Thus stimulatory effects of cortisol on this structure might underlie the cortisol induced enhancement of emotional memory consolidation. The findings presented are in line with models derived from experiments in rodents and are of relevance for our understanding of stress associated psychiatric disorders.

  8. Human attribute concepts: relative ubiquity across twelve mutually isolated languages.

    Science.gov (United States)

    Saucier, Gerard; Thalmayer, Amber Gayle; Bel-Bahar, Tarik S

    2014-07-01

    It has been unclear which human-attribute concepts are most universal across languages. To identify common-denominator concepts, we used dictionaries for 12 mutually isolated languages-Maasai, Supyire Senoufo, Khoekhoe, Afar, Mara Chin, Hmong, Wik-Mungkan, Enga, Fijian, Inuktitut, Hopi, and Kuna-representing diverse cultural characteristics and language families, from multiple continents. A composite list of every person-descriptive term in each lexicon was closely examined to determine the content (in terms of English translation) most ubiquitous across languages. Study 1 identified 28 single-word concepts used to describe persons in all 12 languages, as well as 41 additional terms found in 11 of 12. Results indicated that attribute concepts related to morality and competence appear to be as cross-culturally ubiquitous as basic-emotion concepts. Formulations of universal-attribute concepts from Osgood and Wierzbicka were well-supported. Study 2 compared lexically based personality models on the relative ubiquity of key associated terms, finding that 1- and 2-dimensional models draw on markedly more ubiquitous terms than do 5- or 6-factor models. We suggest that ubiquitous attributes reflect common cultural as well as common biological processes.

  9. Proteomic characterization of human milk whey proteins during a twelve-month lactation period.

    Science.gov (United States)

    Liao, Yalin; Alvarado, Rudy; Phinney, Brett; Lönnerdal, Bo

    2011-04-01

    Human milk is a rich source of bioactive proteins that support the early growth and development of the newborn. Although the major components of the protein fraction in human milk have been studied, the expression and relative abundance of minor components have received limited attention. We examined the expression of low-abundance proteins in the whey fraction of human milk and their dynamic changes over a twelve-month lactation period. The low-abundance proteins were enriched by ProteoMiner beads, and protein identification was performed by liquid chromatography tandem mass spectrometry. One hundred and fifteen proteins were identified, thirty-eight of which have not been previously reported in human colostrum or milk. We also for the first time described differences in protein patterns among the low-abundance proteins during lactation. These results enhance our knowledge about the complexity of the human milk proteome, which constitutes part of the advantages to the breast-fed infant.

  10. Twelve-Month Effects of the COPE Healthy Lifestyles TEEN Program on Overweight and Depressive Symptoms in High School Adolescents

    Science.gov (United States)

    Melnyk, Bernadette M.; Jacobson, Diana; Kelly, Stephanie A.; Belyea, Michael J.; Shaibi, Gabriel Q.; Small, Leigh; O'Haver, Judith A.; Marsiglia, Flavio F.

    2015-01-01

    Background: We evaluated the 12-month effects of the COPE (Creating Opportunities for Personal Empowerment) Healthy Lifestyles TEEN (Thinking, Emotions, Exercise, Nutrition) program versus an attention control program (Healthy Teens) on overweight/obesity and depressive symptoms in high school adolescents. Methods: A cluster randomized controlled…

  11. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans.

    Science.gov (United States)

    Steck, Susan E; Chalecki, Allison M; Miller, Paul; Conway, Jason; Austin, Gregory L; Hardin, James W; Albright, Craig D; Thuillier, Philippe

    2007-05-01

    Conjugated linoleic acid (CLA) alters body composition in animal models, but few studies have examined the effects of CLA supplementation on body composition and clinical safety measures in obese humans. In the present study, we performed a randomized, double-blind, placebo-controlled trial to examine the changes in body composition and clinical laboratory values following CLA (50:50 ratio of cis-9, trans-11 and trans-10, cis-12 isomers) supplementation for 12 wk in otherwise healthy obese humans. Forty-eight participants (13 males and 35 females) were randomized to receive placebo (8 g safflower oil/d), 3.2 g/d CLA, or 6.4 g/d CLA for 12 wk. Changes in body fat mass and lean body mass were determined by dual-energy X-ray absorptiometry. Resting energy expenditure was assessed by indirect calorimetry. Clinical laboratory values and adverse-event reporting were used to monitor safety. Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group (P < 0.05) after 12 wk of intervention. Significant decreases in serum HDL-cholesterol and sodium, hemoglobin, and hematocrit, and significant increases in serum alkaline phosphatase, C-reactive protein, and IL-6, and white blood cells occurred in the 6.4 g/d CLA group, although all values remained within normal limits. The intervention was well tolerated and no severe adverse events were reported, although mild gastrointestinal adverse events were reported in all treatment groups. In conclusion, whereas CLA may increase lean body mass in obese humans, it may also increase markers of inflammation in the short term.

  12. Buen Comienzo, Buen Futuro: El Bebe de Doce Meses (Healthy Start, Grow Smart: Your Twelve-Month-Old).

    Science.gov (United States)

    Landry, Susan H.; Ramey, Craig T.

    Distributed by the U.S. Departments of Agriculture, Education, and Health and Human Services, this Spanish-language pamphlet provides parents with information and advice about their infants in the twelfth month of life. Following a brief description of developmental characteristics at this age, the pamphlet offers advice on a variety of topics,…

  13. DNA methylation and healthy human aging.

    Science.gov (United States)

    Jones, Meaghan J; Goodman, Sarah J; Kobor, Michael S

    2015-12-01

    The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.

  14. Rimonabant effects on anxiety induced by simulated public speaking in healthy humans: a preliminary report.

    Science.gov (United States)

    Bergamaschi, Mateus M; Queiroz, Regina H C; Chagas, Marcos H N; Linares, Ila M P; Arrais, Kátia C; de Oliveira, Danielle C G; Queiroz, Maria E; Nardi, Antonio E; Huestis, Marilyn A; Hallak, Jaime E C; Zuardi, Antonio W; Moreira, Fabrício A; Crippa, José A S

    2014-01-01

    We investigated the hypothesis that rimonabant, a cannabinoid antagonist/inverse agonist, would increase anxiety in healthy subjects during a simulation of the public speaking test. Participants were randomly allocated to receive oral placebo or 90 mg rimonabant in a double-blind design. Subjective effects were measured by Visual Analogue Mood Scale. Physiological parameters, namely arterial blood pressure and heart rate, also were monitored. Twelve participants received oral placebo and 12 received 90 mg rimonabant. Rimonabant increased self-reported anxiety levels during the anticipatory speech and performance phase compared with placebo. Interestingly, rimonabant did not modulate anxiety prestress and was not associated with sedation, cognitive impairment, discomfort, or blood pressure changes. Cannabinoid-1 antagonism magnifies the responses to an anxiogenic stimulus without interfering with the prestress phase. These data suggest that the endocannabinoid system may work on-demand to counteract the consequences of anxiogenic stimuli in healthy humans. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Graff, J

    2008-01-01

    computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. Results......, on gastric volume and gastric emptying after a liquid meal in healthy humans. Material and methods. Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...

  16. Effects of the H2-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J.L.; Graff, J.

    2008-01-01

    computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. RESULTS......, on gastric volume and gastric emptying after a liquid meal in healthy humans. MATERIAL AND METHODS: Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...

  17. [Aspects of healthy humans' response to hyperthermia].

    Science.gov (United States)

    Andreeva, L I; Bannikov, A V; Goranchuk, V V

    1999-01-01

    Single-shot hyperthermia of healthy young men in climate chamber up to rectal temperature of 39.5 degrees C over 75-110 minutes revealed variable heat resistance. Individuals with prevalent sympathetic vegetative regulation were more resistant to overheating, if compared to those with prevalent parasympathetic one. Endocrine group peculiarities were observed, the examinees with prevalent parasympathetic vegetative regulation demonstrated more drastic changes of some biochemical parameters.

  18. Diversity of bacteria at healthy human conjunctiva.

    Science.gov (United States)

    Dong, Qunfeng; Brulc, Jennifer M; Iovieno, Alfonso; Bates, Brandon; Garoutte, Aaron; Miller, Darlene; Revanna, Kashi V; Gao, Xiang; Antonopoulos, Dionysios A; Slepak, Vladlen Z; Shestopalov, Valery I

    2011-07-20

    Ocular surface (OS) microbiota contributes to infectious and autoimmune diseases of the eye. Comprehensive analysis of microbial diversity at the OS has been impossible because of the limitations of conventional cultivation techniques. This pilot study aimed to explore true diversity of human OS microbiota using DNA sequencing-based detection and identification of bacteria. Composition of the bacterial community was characterized using deep sequencing of the 16S rRNA gene amplicon libraries generated from total conjunctival swab DNA. The DNA sequences were classified and the diversity parameters measured using bioinformatics software ESPRIT and MOTHUR and tools available through the Ribosomal Database Project-II (RDP-II). Deep sequencing of conjunctival rDNA from four subjects yielded a total of 115,003 quality DNA reads, corresponding to 221 species-level phylotypes per subject. The combined bacterial community classified into 5 phyla and 59 distinct genera. However, 31% of all DNA reads belonged to unclassified or novel bacteria. The intersubject variability of individual OS microbiomes was very significant. Regardless, 12 genera-Pseudomonas, Propionibacterium, Bradyrhizobium, Corynebacterium, Acinetobacter, Brevundimonas, Staphylococci, Aquabacterium, Sphingomonas, Streptococcus, Streptophyta, and Methylobacterium-were ubiquitous among the analyzed cohort and represented the putative "core" of conjunctival microbiota. The other 47 genera accounted for ocular surface pathogens. The first DNA sequencing-based survey of bacterial population at the conjunctiva have revealed an unexpectedly diverse microbial community. All analyzed samples contained ubiquitous (core) genera that included commensal, environmental, and opportunistic pathogenic bacteria.

  19. The North/South Debate: Technology, Basic Human Needs and the New International Economic Order. Working Paper Number Twelve. 1980.

    Science.gov (United States)

    Galtung, Johan

    This document contains two articles by Johan Galtung presented as papers at an international conference on the relationship of technology to the environment and human needs. The monograph is part of a series intended to stimulate research, education, dialogue, and political action toward a just world order. The first paper, "Towards a New…

  20. The North/South Debate: Technology, Basic Human Needs and the New International Economic Order. Working Paper Number Twelve. 1980.

    Science.gov (United States)

    Galtung, Johan

    This document contains two articles by Johan Galtung presented as papers at an international conference on the relationship of technology to the environment and human needs. The monograph is part of a series intended to stimulate research, education, dialogue, and political action toward a just world order. The first paper, "Towards a New…

  1. Characterizing healthy samples for studies of human cognitive aging

    OpenAIRE

    Geldmacher, David S.; Levin, Bonnie E.; Wright, Clinton B.

    2012-01-01

    Characterizing the cognitive declines associated with aging, and differentiating them from the effects of disease in older adults, are important goals for human neuroscience researchers. This is also an issue of public health urgency in countries with rapidly aging populations. Progress toward understanding cognitive aging is complicated by numerous factors. Researchers interested in cognitive changes in healthy older adults need to consider these complexities when they design and interpre...

  2. Scaling Behaviour and Memory in Heart Rate of Healthy Human

    Institute of Scientific and Technical Information of China (English)

    CAI Shi-Min; PENG Hu; YANG Hui-Jie; ZHOU Tao; ZHOU Pei-Ling; WANG Bing-Hong

    2007-01-01

    We investigate a set of complex heart rate time series from healthy human in different behaviour states with the detrended fluctuation analysis and diffusion entropy (DE) method. It is proposed that the scaling properties are influenced by behaviour states. The memory detected by DE exhibits an approximately same pattern after a detrending procedure. Both of them demonstrate the long-range strong correlations in heart rate. These findings may be helpful to understand the underlying dynamical evolution process in the heart rate control system, as well as to model the cardiac dynamic process.

  3. Albuterol Improves Alveolar-Capillary Membrane Conductance in Healthy Humans

    Science.gov (United States)

    Taylor, Natalie E.; Baker, Sarah E.; Olson, Thomas P.; Lalande, Sophie; Johnson, Bruce D.; Snyder, Eric M.

    2016-01-01

    BACKGROUND Beta-2 adrenergic receptors (β2ARs) are located throughout the body including airway and alveolar cells. The β2ARs regulate lung fluid clearance through a variety of mechanisms including ion transport on alveolar cells and relaxation of the pulmonary lymphatics. We examined the effect of an inhaled β2-agonist (albuterol) on alveolar-capillary membrane conductance (DM) and pulmonary capillary blood volume (VC) in healthy humans. METHODS We assessed the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) at baseline, 30 minutes, and 60 minutes following nebulized albuterol (2.5 mg, diluted in 3 mL normal saline) in 45 healthy subjects. Seventeen subjects repeated these measures following nebulized normal saline (age = 27 ± 9 years, height = 165 ± 21 cm, weight = 68 ± 12 kg, BMI = 26 ± 9 kg/m2). Cardiac output (Q), heart rate, systemic vascular resistance (SVR), blood pressure, oxygen saturation, forced expiratory volume at one-second (FEV1), and forced expiratory flow at 50% of forced vital capacity (FEF50) were assessed at baseline, 30 minutes, and 60 minutes following the administration of albuterol or saline. RESULTS Albuterol resulted in a decrease in SVR, and an increase in Q, FEV1, and FEF50 compared to saline controls. Albuterol also resulted in a decrease in VC at 60 minutes post albuterol. Both albuterol and normal saline resulted in no change in DLCO or DM when assessed alone, but a significant increase was observed in DM when accounting for changes in VC. CONCLUSION These data suggest that nebulized albuterol improves pulmonary function in healthy humans, while nebulization of both albuterol and saline results in an increase in DM/VC. PMID:27773996

  4. Gastroprotection induced by capsaicin in healthy human subjects

    Institute of Scientific and Technical Information of China (English)

    Gyula Mózsik; János Szolcsányi; István Rácz

    2005-01-01

    AIM: To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin (IND)-induced gastric mucosal damage in healthy human subjects.METHODS: The effects of small doses (1-8 μg/mL,100 mL) of capsaicin on the gastric acid secretion basal acid output (BAO) and its electrolyte concentration,gastric transmucosal potential difference (GTPD),ethanol- (5 mL 300 mL/L i.g.) and IND- (3x25 mg/d)induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment.RESULTS: Intragastric application of capsaicin decreased the BAO and enhanced "non-parietal" component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application,which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin,but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3x400 μg i.g.CONCLUSION: Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.

  5. Modest Visceral Fat Gain Causes Endothelial Dysfunction In Healthy Humans

    Science.gov (United States)

    Romero-Corral, Abel; Sert-Kuniyoshi, Fatima H.; Sierra-Johnson, Justo; Orban, Marek; Gami, Apoor; Davison, Diane; Singh, Prachi; Pusalavidyasagar, Snigdha; Huyber, Christine; Votruba, Susanne; Lopez-Jimenez, Francisco; Jensen, Michael D.; Somers, Virend K.

    2014-01-01

    Objective This study sought to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. Background Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. Methods A randomized controlled study to assess the effects of fat gain on endothelial function. We recruited 43 normal weight healthy volunteers (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n=35) or to maintain weight (n=8). Endothelial function (brachial artery flow mediated dilation -FMD) was measured at baseline, after fat gain (8 weeks) and after weight loss (16 weeks) for fat-gainers and at baseline and follow-up (8 weeks) for weight-maintainers. Body composition was measured by DXA and abdominal CT scans. Results After an average weight gain of 4.1 kg, fat-gainers significantly increased their total, visceral and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight-maintainers. FMD decreased in fat-gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p =0.003), but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = −0.42, p=0.004), but not with subcutaneous fat gain (rho = −0.22, p=0.15). Conclusions In normal weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. PMID:20705223

  6. A review of the volatiles from the healthy human body.

    Science.gov (United States)

    de Lacy Costello, B; Amann, A; Al-Kateb, H; Flynn, C; Filipiak, W; Khalid, T; Osborne, D; Ratcliffe, N M

    2014-03-01

    A compendium of all the volatile organic compounds (VOCs) emanating from the human body (the volatolome) is for the first time reported. 1840 VOCs have been assigned from breath (872), saliva (359), blood (154), milk (256), skin secretions (532) urine (279), and faeces (381) in apparently healthy individuals. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been grouped into tables according to their chemical class or functionality to permit easy comparison. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces. Careful use of the database is needed. The numbers may not be a true reflection of the actual VOCs present from each bodily excretion. The lack of a compound could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from blood compared to a large number on VOCs in breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. collecting excretions on glass beads and then heating to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors' intention that this database will not only be a useful database of VOCs listed in the literature, but will stimulate further study of VOCs from healthy individuals. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.

  7. Chromosomal abnormalities in human sperm: comparisons among four healthy men

    Energy Technology Data Exchange (ETDEWEB)

    Brandriff, B.; Gordon, L.; Ashworth, L.; Watchmaker, G.; Carrano, A.; Wyrobek, A.

    1984-01-01

    The human-sperm/hamster-egg system has been used to compare the frequencies of structural and numerical chromosomal aberrations in 909 sperm karyotypes from four normal healthy men. The frequency of structural aberrations was 1.3, 4.8, 9.0, and 10.4% respectively in the four donors. Certain specific breakpoints were seen twice or even three times in three of the donors. The incidence of aneuploidy was 1.3, 1.4, 1.4, and 1.9%. In three donors the frequencies of structural aberrations were significantly higher in sperm than in lymphocytes from the same man. X-to-Y ratios did not differ significantly from the expected 50:50. 37 references, 4 figures, 5 tables.

  8. Repeated assessment of exploration and novelty seeking in the human behavioral pattern monitor in bipolar disorder patients and healthy individuals.

    Directory of Open Access Journals (Sweden)

    Arpi Minassian

    Full Text Available BACKGROUND: Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM, a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD. METHODOLOGY AND PRINCIPAL FINDINGS: Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions. CONCLUSIONS/SIGNIFICANCE: Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design

  9. Intravenous Glucose Acutely Stimulates Intestinal Lipoprotein Secretion in Healthy Humans.

    Science.gov (United States)

    Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Lewis, Gary F

    2016-07-01

    Increased production of intestinal triglyceride-rich lipoproteins (TRLs) contributes to dyslipidemia and increased risk of atherosclerotic cardiovascular disease in insulin resistance and type 2 diabetes. We have previously demonstrated that enteral glucose enhances lipid-stimulated intestinal lipoprotein particle secretion. Here, we assessed whether glucose delivered systemically by intravenous infusion also enhances intestinal lipoprotein particle secretion in humans. On 2 occasions, 4 to 6 weeks apart and in random order, 10 healthy men received a constant 15-hour intravenous infusion of either 20% glucose to induce hyperglycemia or normal saline as control. Production of TRL-apolipoprotein B48 (apoB48, primary outcomes) and apoB100 (secondary outcomes) was assessed during hourly liquid-mixed macronutrient formula ingestion with stable isotope enrichment and multicompartmental modeling, under pancreatic clamp conditions to limit perturbations in pancreatic hormones (insulin and glucagon) and growth hormone. Compared with saline infusion, glucose infusion induced both hyperglycemia and hyperinsulinemia, increased plasma triglyceride levels, and increased TRL-apoB48 concentration and production rate (Plipoprotein production. Hyperglycemia may contribute to intestinal lipoprotein overproduction in type 2 diabetes. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02607839. © 2016 American Heart Association, Inc.

  10. Sympathetic nerve activity and simulated diving in healthy humans.

    Science.gov (United States)

    Shamsuzzaman, Abu; Ackerman, Michael J; Kuniyoshi, Fatima Sert; Accurso, Valentina; Davison, Diane; Amin, Raouf S; Somers, Virend K

    2014-04-01

    The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome.

  11. Effects of regional phentolamine on hypoxic vasodilatation in healthy humans.

    Science.gov (United States)

    Weisbrod, C J; Minson, C T; Joyner, M J; Halliwill, J R

    2001-12-01

    1. Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of beta-adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation approximately 85%) in eight healthy men and women (18-26 years) after selective alpha-adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined alpha- and beta-adrenergic blockade (phentolamine and propranolol) and after combined alpha- and beta-adrenergic blockade coupled with NO synthase inhibition (N(G)-monomethyl-L-arginine, L-NMMA). 3. Hypoxia increased forearm vascular conductance by 49.0 +/- 13.5% after phentolamine (compared to +16.8 +/- 7.0% in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by approximately 50%, but dilatation was still present (+24.7 +/- 7.0%, P < 0.05 vs. normoxia). When L-NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 +/- 4.0%, P < 0.05 vs. normoxia). 4. Thus, selective regional alpha-adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by beta-adrenergic receptor-mediated pathways. Finally, since considerable dilatation persists in the presence of both beta-adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.

  12. The Twelve Hotel, Barna : Video

    OpenAIRE

    Irish Food Channel

    2014-01-01

    Fergus O'Halloran, Managing Director of The Twelve Hotel in Barna in County Galway, talks about his philosophy in running this unique boutique hotel. Reproduced with kind permission from John & Sally McKenna. 3.35 mins

  13. Goal-directed fluid therapy: stroke volume optimisation and cardiac dimensions in supine healthy humans

    DEFF Research Database (Denmark)

    Jans, O.; Tollund, C.; Bundgaard-Nielsen, M.

    2008-01-01

    by thoracic electrical admittance, central venous oxygenation and pressure, and arterial plasma atrial natriuretic peptide. Also, muscle and brain oxygenation were assessed by near infrared spectroscopy (n=7). RESULTS: The HUT reduced the mentioned indices of CBV, the end-diastolic dimensions of the heart...... to head-up (HUT) and head-down tilt (HDT). METHODS: Twelve healthy volunteers underwent graded tilt from 20 degrees HDT to 30 degrees HUT. The end-diastolic dimensions of the heart were assessed by transthoracic echocardiography with independent evaluation of SV by Modelflow. The CBV was monitored...

  14. The Effects of Twelve Weeks of Tai Chi Practice on Anxiety in Stressed But Healthy People Compared to Exercise and Wait-List Groups-A Randomized Controlled Trial.

    Science.gov (United States)

    Zheng, Shuai; Kim, Christine; Lal, Sara; Meier, Peter; Sibbritt, David; Zaslawski, Chris

    2017-06-13

    This randomized controlled trial was undertaken to determine whether 12 weeks of Tai Chi (TC) practice can reduce anxiety in healthy but stressed people. Fifty participants were randomized into TC (n=17), exercise (n=17), and wait-list (WL) groups (n=16). Outcome measures used were State Trait Anxiety Inventory, Perceived Stress Scale 14 (PSS14), blood pressure and heart rate variability, visual analogue scale (VAS), and Short Form 36. Significant improvements were observed from baseline for both TC and exercise groups for both state (p stress levels in healthy individuals and provides a safer, cost effective, and less physically vigorous alternative to exercise. © 2017 Wiley Periodicals, Inc.

  15. Decreases in Human Semen Quality with Age Among Healthy Men

    Energy Technology Data Exchange (ETDEWEB)

    Eskenazi, B.; Wyrobek, A.J.; Kidd, S.A.; Moore, L.; Young, S.S.; Moore, D.

    2001-12-01

    The objective of this report is to characterize the associations between age and semen quality among healthy active men after controlling for identified covariates. Ninety-seven healthy, nonsmoking men between 22 and 80 years without known fertility problems who worked for or retired from a large research laboratory. There was a gradual decrease in all semen parameters from 22-80 years of age. After adjusting for covariates, volume decreased 0.03 ml per year (p = 0.001); sperm concentration decreased 2.5% per year (p = 0.005); total count decreased 3.6% per year of age (p < 0.001); motility decreased 0.7% per year (P < 0.001); progressive motility decreased 3.1% per year (p < 0.001); and total progressively motile sperm decreased 4.8% per year (p < 0.001). In a group of healthy active men, semen volume, sperm concentration, total sperm count, and sperm motility decrease continuously between 22-80 years of age, with no evidence of a threshold.

  16. Motor threshold predicts working memory performance in healthy humans.

    Science.gov (United States)

    Schicktanz, Nathalie; Schwegler, Kyrill; Fastenrath, Matthias; Spalek, Klara; Milnik, Annette; Papassotiropoulos, Andreas; Nyffeler, Thomas; de Quervain, Dominique J-F

    2014-01-01

    Cognitive functions, such as working memory, depend on neuronal excitability in a distributed network of cortical regions. It is not known, however, if interindividual differences in cortical excitability are related to differences in working memory performance. In the present transcranial magnetic stimulation study, which included 188 healthy young subjects, we show that participants with lower resting motor threshold, which is related to higher corticospinal excitability, had increased 2-back working memory performance. The findings may help to better understand the link between cortical excitability and cognitive functions and may also have important clinical implications with regard to conditions of altered cortical excitability.

  17. Intestinal Microbiota Distinguish Gout Patients from Healthy Humans.

    Science.gov (United States)

    Guo, Zhuang; Zhang, Jiachao; Wang, Zhanli; Ang, Kay Ying; Huang, Shi; Hou, Qiangchuan; Su, Xiaoquan; Qiao, Jianmin; Zheng, Yi; Wang, Lifeng; Koh, Eileen; Danliang, Ho; Xu, Jian; Lee, Yuan Kun; Zhang, Heping

    2016-02-08

    Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota.

  18. Mathematical Model for Hemodynamicand Hormonal Effects of Human Ghrelin in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Geetha.T

    2014-11-01

    Full Text Available Hemodynamicand hormonal effects of human ghrelin in healthy volunteers.To investigate hemodynamic and hormonaleffects of ghrelin, a novel growth hormone (GH-releasing peptide, we gave six healthy men an intravenousbolus of human ghrelin or placebo and vice versa1–2 wk apart in a randomized fashion. Ghrelin elicited amarked increase in circulating GH . The elevation ofGH lasted longer than 60 min after the bolus injection.Injection of ghrelin significantly decreased mean arterialpressure without a significant changein heart rate .In summary, human ghrelin elicited a potent, longlastingGH release and had beneficial hemodynamic effectsvia reducing cardiac afterload and increasing cardiac outputwithout an increase in heart rate. Thus, the purpose of thisstudy was to investigate hemodynamic and hormonaleffects of intravenous ghrelin in healthy volunteers. This paper discussed the constant stress level of healthy volunteers with times to damage of stress effect andrecoveries

  19. Survival function Of Realization process for Hemodynamic and hormonal effects of human GH in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Geetha.T

    2014-12-01

    Full Text Available Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin or placebo and vice versa 1–2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH. The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure without a significant change in heart rate .In summary, human ghrelin elicited a potent, long lasting GH release and had beneficial hemodynamic effects via reducing cardiac after load and increasing cardiac output without an increase in heart rate. Thus, the purpose of this study was to investigate hemodynamic and hormonal effects of intravenous ghrelin in healthy volunteers. This paper discussed the constant stress level of healthy volunteers with times to damage of stress effect and recoveries

  20. Gastroenteric hormone responses to hedonic eating in healthy humans.

    Science.gov (United States)

    Monteleone, Palmiero; Scognamiglio, Pasquale; Monteleone, Alessio Maria; Perillo, Donato; Canestrelli, Benedetta; Maj, Mario

    2013-08-01

    Hedonic eating differentiates from homeostatic eating on two main aspects: the first one is that eating occurs when there is no need for calorie ingestion and the second one is that the food is consumed exclusively for its gustatory and rewarding properties. Gastroeneteric hormones such as ghrelin, colecystokinin-33 (CCK) and peptide YY3-36 (PYY3-36) are known to play a pivotal role in the homeostatic control of food intake. To the contrary, their role in hedonic eating has been never investigated. Here we report peripheral responses of CCK, PYY3-36 and ghrelin to the consumption of food for pleasure in well-nourished satiated healthy subjects. Plasma levels of CCK, PYY3-36 and ghrelin were measured in 7 satiated healthy subjects before and after ad libitum consumption of both a highly pleasurable food (hedonic eating) and an isoenergetic non-pleasurable food (non-hedonic eating). The consumption of food for pleasure was associated to a significantly increased production of the hunger hormone ghrelin and a significantly decreased secretion of the satiety hormone CCK. No significant changes in plasma PYY3-36 levels occurred in the two eating conditions. These preliminary data demonstrate that in hedonic eating the peripheral hunger signal represented by ghrelin secretion is enhanced while the satiety signal of CCK production is decreased. This could be responsible for the persistence of peripheral cues allowing a continued eating as well as for the activation of endogenous reward mechanisms, which can drive food consumption in spite of no energy need, only for reward. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. GeXP多重PCR技术同时检测12种常见呼吸道病毒%A GeXP based Multiplex RT-PCR Assay for Simultaneous Detection of Twelve Human Respiratory Viruses

    Institute of Scientific and Technical Information of China (English)

    李瑾; 毛乃颖; 秦萌; 胡秀梅; 杨梦婕; 王淼; 张晨; 许文波; 马学军

    2011-01-01

    本研究建立了一种基于GeXP多重基因表达遗传分析系统的多重RT-PCR检测方法,该方法可以同时检测12种呼吸道病毒,包括流感病毒A型和B型、季节性H1N1、副流感病毒1~3型、人鼻病毒、人偏肺病毒、腺病毒、呼吸道合胞病毒A型和B型、人博卡病毒.针对病原体保守区序列设计12种病毒的特异性引物,分别用已验证的阳性标本为模板检验多重体系的特异性.多重检测体系在103拷贝/μL水平可同时检测到12种病毒.另检测24份临床标本,以real-time RT-PCR为参考标准,进一步验证检测体系.结果表明,这种基于GeXP系统的新方法灵敏度高、特异性强,可以快速同时检测12种常见呼吸道病毒.%A GeXP based multiplex RT-PCR assay was developed to simultaneously detect twelve different respiratory viruses types/subtypes including influenza A virus, influenza B virus, influenza A virus sHlNl, parainfluenza virus type 1, parainfluenza virus type 2, parainfluenza virus type 3 , human rhinovi-rus, human metapneumovirus, adenovirus, respiratory syncytial virus A, respiratory syncytial virus B and human bocavirus. Twelve sets of specific primers were designed based on the conserved sequences of available respiratory-virus sequence database The specificity of the multiplex system was examined by positive specimens confirmed previously. The sensitivity to detect twelve respiratory viruses simultaneously was 103 copies/μL. Twenty four clinical specimens were further detected by this novel assay and the results were compared with that of the real-time RT-PCR. These results showed that this novel assay based on GeXP is a fast, sensitive, and high throughput test for the detection of respiratory virus infections.

  2. Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity

    Science.gov (United States)

    Germain, Natacha; Viltart, Odile; Loyens, Anne; Bruchet, Céline; Nadin, Katia; Wolowczuk, Isabelle; Estour, Bruno; Galusca, Bogdan

    2016-01-01

    Introduction Interleukin-7 (IL-7) is a cytokine involved in energy homeostasis as demonstrated in rodents. Anorexia nervosa is characterized by restrained eating behavior despite adaptive orexigenic regulation profile including high ghrelin plasma levels. Constitutional thinness is a physiological condition of resistance to weight gain with physiological anorexigenic profile including high Peptide YY plasma level. Healthy obesity can be considered as a physiological state of resistance to weight loss with opposite appetite regulating profile to constitutional thinness including low Peptide YY plasma level. No studies in IL-7 are yet available in those populations. Therefore we evaluated circadian plasma levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy obese and control females. Materials and Methods 10 restrictive-type anorexia nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7 healthy obese females, and 10 normal weight women controls were enrolled in this cross-sectional study, performed in endocrinology unit and academic laboratory. Twelve-point circadian profiles of plasma IL-7 levels were measured in each subject. Results 24h mean IL-7 plasma levels (pg/ml, mean±SEM) were decreased in restrictive-type anorexia nervosa (123.4±14.4, pobese patients (51±3.2, pobesity, with low IL-7, is once again in mirror image of constitutional thinness with normal high IL-7. PMID:27611669

  3. Hemispheric asymmetry and somatotopy of afferent inhibition in healthy humans.

    Science.gov (United States)

    Helmich, R C G; Bäumer, T; Siebner, H R; Bloem, B R; Münchau, A

    2005-11-01

    A conditioning electrical stimulus to a digital nerve can inhibit the motor-evoked potentials (MEPs) in adjacent hand muscles elicited by transcranial magnetic stimulation (TMS) to the contralateral primary motor cortex (M1) when given 25-50 ms before the TMS pulse. This is referred to as short-latency afferent inhibition (SAI). We studied inter-hemispheric differences (Experiment 1) and within-limb somatotopy (Experiment 2) of SAI in healthy right-handers. In Experiment 1, conditioning electrical pulses were applied to the right or left index finger (D2) and MEPs were recorded from relaxed first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles ipsilateral to the conditioning stimulus. We found that SAI was more pronounced in right hand muscles. In Experiment 2, electrical stimulation was applied to the right D2 and MEPs were recorded from ipsilateral FDI, extensor digitorum communis (EDC) and biceps brachii (BB) muscles. The amount of SAI did not differ between FDI, EDC and BB muscles. These data demonstrate inter-hemispheric differences in the processing of cutaneous input from the hand, with stronger SAI in the dominant left hemisphere. We also found that SAI occurred not only in hand muscles adjacent to electrical digital stimulation, but also in distant hand and forearm and also proximal arm muscles. This suggests that SAI induced by electrical D2 stimulation is not focal and somatotopically specific, but a more widespread inhibitory phenomenon.

  4. Genotype and ancestry modulate brain's DAT availability in healthy humans.

    Directory of Open Access Journals (Sweden)

    Elena Shumay

    Full Text Available The dopamine transporter (DAT is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3 is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET with [¹¹C]cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms--3-UTR- and intron 8--VNTRs. The main findings are the following: 1 both polymorphisms analyzed as single genetic markers and in combination (haplotype modulate DAT density in midbrain; 2 ethnic background and age influence the strength of these associations; and 3 age-related changes in DAT availability differ in the 3-UTR and intron 8--genotype groups.

  5. Oxygen challenge magnetic resonance imaging in healthy human volunteers.

    Science.gov (United States)

    Dani, Krishna A; Moreton, Fiona C; Santosh, Celestine; Lopez, Rosario; Brennan, David; Schwarzbauer, Christian; Goutcher, Colin; O'Hare, Kevin; Macrae, I Mhairi; Muir, Keith W

    2017-01-01

    Oxygen challenge imaging involves transient hyperoxia applied during deoxyhaemoglobin sensitive (T2*-weighted) magnetic resonance imaging and has the potential to detect changes in brain oxygen extraction. In order to develop optimal practical protocols for oxygen challenge imaging, we investigated the influence of oxygen concentration, cerebral blood flow change, pattern of oxygen administration and field strength on T2*-weighted signal. Eight healthy volunteers underwent multi-parametric magnetic resonance imaging including oxygen challenge imaging and arterial spin labelling using two oxygen concentrations (target FiO2 of 100 and 60%) administered consecutively (two-stage challenge) at both 1.5T and 3T. There was a greater signal increase in grey matter compared to white matter during oxygen challenge (p challenge imaging. Reductions in cerebral blood flow did not obscure the T2*-weighted signal increases. In conclusion, the optimal protocol for further study should utilise target FiO2 = 100% during a single oxygen challenge. Imaging at both 1.5T and 3T is clinically feasible.

  6. Neural coding of movement direction in the healthy human brain.

    Directory of Open Access Journals (Sweden)

    Christopher D Cowper-Smith

    Full Text Available Neurophysiological studies in monkeys show that activity of neurons in primary cortex (M1, pre-motor cortex (PMC, and cerebellum varies systematically with the direction of reaching movements. These neurons exhibit preferred direction tuning, where the level of neural activity is highest when movements are made in the preferred direction (PD, and gets progressively lower as movements are made at increasing degrees of offset from the PD. Using a functional magnetic resonance imaging adaptation (fMRI-A paradigm, we show that PD coding does exist in regions of the human motor system that are homologous to those observed in non-human primates. Consistent with predictions of the PD model, we show adaptation (i.e., a lower level of the blood oxygen level dependent (BOLD time-course signal in M1, PMC, SMA, and cerebellum when consecutive wrist movements were made in the same direction (0° offset relative to movements offset by 90° or 180°. The BOLD signal in dorsolateral prefrontal cortex adapted equally in all movement offset conditions, mitigating against the possibility that the present results are the consequence of differential task complexity or attention to action in each movement offset condition.

  7. How healthy is the human-ocean system?

    Science.gov (United States)

    Rickels, Wilfried; Quaas, Martin F.; Visbeck, Martin

    2014-04-01

    Halpern et al (2012 An index to assess the health and benefits of the global ocean Nature 488 11397) propose a detailed measure of the state of the human-ocean system against ten societal goals. They devote less attention to the normative foundation of the index, which is crucial for assessing the overall health of the human-ocean system, notably when it comes to aggregation of potentially conflicting goals. Social choice theory provides several possible functional forms for assessing the compound change in various goals. The one chosen by Halpern et al, the arithmetical mean, is not only a specific but also an extreme case. It implicitly allows for unlimited substitution. A one-unit reduction in one goal can be fully offset by a one-unit increase in another with the same weighting factor. For that reason, the current index satisfies an extremely weak sustainability concept. We show that the results in Halpern et al are not robust when one adopts a strong sustainability concept. The overall health score of the ocean decreases, the ranking of the various coastal states changes substantially, and the assessment of sustainable development needs to be partially reversed.

  8. Quantification of MRI measured myocardial perfusion reserve in healthy humans: a comparison with positron emission tomography

    DEFF Research Database (Denmark)

    Fritz-Hansen, Thomas; Hove, Jens D; Kofoed, Klaus F

    2008-01-01

    PURPOSE: To validate a noninvasive quantitative MRI technique, the K(i) perfusion method, for myocardial perfusion in humans using (13)N-ammonia PET as a reference method. MATERIALS AND METHODS: Ten healthy males (64 +/- 8 years) were examined with combined PET and MRI perfusion imaging at rest...... and during stress induced by dipyridamole in order to determine the myocardial perfusion reserve. Myocardial and blood time concentration curves obtained by Gd-DTPA-enhanced MRI and (13)N-ammonia PET were fitted by a two-compartment perfusion model. RESULTS: Mean perfusion values (+/-SD) derived from the MRI...... as a quantitative marker for myocardial perfusion in healthy humans....

  9. Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects.

    Science.gov (United States)

    Shores, M M; Pascualy, M; Lewis, N L; Flatness, D; Veith, R C

    2001-05-01

    Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 microg/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions.

  10. The effects of eating marine- or vegetable-fed farmed trout on the human plasma proteome profiles of healthy men.

    Science.gov (United States)

    Rentsch, Maria L; Lametsch, René; Bügel, Susanne; Jessen, Flemming; Lauritzen, Lotte

    2015-02-28

    Most human intervention studies have examined the effects on a subset of risk factors, some of which may require long-term exposure. The plasma proteome may reflect the underlying changes in protein expression and activation, and this could be used to identify early risk markers. The aim of the present study was to evaluate the impact of regular fish intake on the plasma proteome. We recruited thirty healthy men aged 40 to 70 years, who were randomly allocated to a daily meal of chicken or trout raised on vegetable or marine feeds. Blood samples were collected before and after 8 weeks of intervention, and after the removal of the twelve most abundant proteins, plasma proteins were separated by two-dimensional gel electrophoresis. Protein spots 4·3 visualised by silver staining were matched by two-dimensional imaging software. Within-subject changes in spots were compared between the treatment groups. Differentially affected spots were identified by matrix-assisted laser desorption ionisation-time of flight/time of flight MS and the human Swiss-Prot database. We found 23/681 abundant plasma protein spots, which were up- or down-regulated by the dietary treatment (P spots differed from those in subjects given the chicken meal, but only three of these were common, and only one spot differed between the two trout groups. In both groups, the affected plasma proteins were involved in biological processes such as regulation of vitamin A and haem transport, blood fibrinolysis and oxidative defence. Thus, regular fish intake affects the plasma proteome, and the changes may indicate novel mechanisms of effect.

  11. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.

    Directory of Open Access Journals (Sweden)

    Anthony E Civitarese

    2007-03-01

    Full Text Available Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood.The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y, overweight (body mass index, 27.8 +/- 0.7 kg/m(2 individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX, 12.5% CR + 12.5% increased energy expenditure (EE. In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008. Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05. In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005 and 21% +/- 4% in the CREX group (p < 0.004, with no change in the control group (2% +/- 2%. However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid cycle (citrate synthase, beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase, and electron transport chain (cytochrome C oxidase II was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003 and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011, but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR.The observed increase in

  12. Associations between human rights environments and healthy longevity: the case of older persons in China.

    Science.gov (United States)

    Brown, Bethany L; Qiu, Li; Gu, Danan

    2012-12-15

    Individual health can deteriorate through neglect or violation of human rights or can improve through favorable health policies and programs on human rights. Yet quantitative associations between human rights and health are insufficiently studied. Based on a nationwide dataset of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with more than 18,800 adults aged 65 and older in mainland China interviewed in 2002 and 2005 and their follow-ups three years later, we examine how an individual's longevity and health are associated with some domains of human rights. We use three individual-level variables in early life stages (whether a respondent went to bed hungry, accessed adequate medical services, and years of schooling), three individual-level variables at present (whether a respondent has adequate housing; whether a respondent has adequate economic resources to support his/her daily subsistence, and whether a respondent gets adequate medical services when in need), and one community-level variable (air quality) as proxies to measure several fundamental domains of human rights in terms of access to adequate food/nutrition, housing/shelter, education, social security, health care, and clean-air environments. An indicator of healthy survival is introduced to measure survivors at sequent follow-ups with a good health condition. Our results demonstrate that better conditions of proxy measures of human rights at different life stages, especially at present, are associated with a higher likelihood of healthy survival after taking various confounding variables into consideration, suggesting the possibility of a significant linkage between good environments in human rights and healthy longevity. These findings may have important implications for promoting better environments in human rights, especially in the context of population aging.

  13. HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging.

    Science.gov (United States)

    Jazwinski, S Michal; Kim, Sangkyu; Dai, Jianliang; Li, Li; Bi, Xiuhua; Jiang, James C; Arnold, Jonathan; Batzer, Mark A; Walker, Jerilyn A; Welsh, David A; Lefante, Christina M; Volaufova, Julia; Myers, Leann; Su, L Joseph; Hausman, Dorothy B; Miceli, Michael V; Ravussin, Eric; Poon, Leonard W; Cherry, Katie E; Welsch, Michael A

    2010-10-01

    The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.

  14. The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota.

    Science.gov (United States)

    Scanlan, Pauline D; Stensvold, Christen R; Rajilić-Stojanović, Mirjana; Heilig, Hans G H J; De Vos, Willem M; O'Toole, Paul W; Cotter, Paul D

    2014-10-01

    To date, the majority of research into the human gut microbiota has focused on the bacterial fraction of the community. Inevitably, this has resulted in a poor understanding of the diversity and functionality of other intestinal microorganisms in the human gut. One such nonbacterial member is the microbial eukaryote Blastocystis, which has been implicated in the aetiology of a range of different intestinal and extra-intestinal diseases. However, prevalence data from different studies are conflicting, and crucially, there is limited information on its incidence and diversity in healthy individuals. Here, we survey the prevalence, genetic diversity and temporal stability of Blastocystis in a group of healthy adults (n = 105) using a sensitive PCR assay. Blastocystis was present in 56% of our sample set, which is much higher than previously reported from an industrialised county (Ireland). Moreover, a diversity of different subtypes (species) were detected, and Blastocystis was present in a subset of individuals sampled over a period of time between 6 and 10 years, indicating that it is capable of long-term host colonisation. These results show that Blastocystis is a common and diverse member of the healthy gut microbiota, thereby extending our knowledge of the microbial ecology of the healthy human intestine. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  15. Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

    Science.gov (United States)

    Giannini, C.; Siliqi, D.; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

    2012-01-01

    Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections. PMID:22666538

  16. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  17. Occurrence of human pathogenic Clostridium botulinum among healthy dairy animals: an emerging public health hazard.

    Science.gov (United States)

    Abdel-Moein, Khaled A; Hamza, Dalia A

    2016-01-01

    The current study was conducted to investigate the occurrence of human pathogenic Clostridium botulinum in the feces of dairy animals. Fecal samples were collected from 203 apparently healthy dairy animals (50 cattle, 50 buffaloes, 52 sheep, 51 goats). Samples were cultured to recover C. botulinum while human pathogenic C. botulinum strains were identified after screening of all C. botulinum isolates for the presence of genes that encode toxins type A, B, E, F. The overall prevalence of C. botulinum was 18.7% whereas human pathogenic C. botulinum strains (only type A) were isolated from six animals at the rates of 2, 2, 5.8, and 2% for cattle, buffaloes, sheep, and goats, respectively. High fecal carriage rates of C. botulinum among apparently healthy dairy animals especially type A alarm both veterinary and public health communities for a potential role which may be played by dairy animals in the epidemiology of such pathogen.

  18. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  19. Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

    Science.gov (United States)

    Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

    2014-01-01

    As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

  20. Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans.

    Science.gov (United States)

    Coletta, Marina; Gates, Fred K; Marciani, Luca; Shiwani, Henna; Major, Giles; Hoad, Caroline L; Chaddock, Gemma; Gowland, Penny A; Spiller, Robin C

    2016-01-14

    Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

  1. Transanal rectopexy - twelve case studies

    Directory of Open Access Journals (Sweden)

    Rubens Henrique Oleques Fernandes

    2012-06-01

    Full Text Available OBJECTIVES: This study analyzed the results of transanal rectopexy and showed the benefits of this surgical technique. METHOD: Twelve patients were submitted to rectopexy between 1997 and 2011. The surgical technique used was transanal rectopexy, where the mesorectum was fixed to the sacrum with nonabsorbable suture. Three patients had been submitted to previous surgery, two by the Delorme technique and one by the Thiersch technique. RESULTS: Postoperative hospital stay ranged from 1 to 4 days. One patient (8.3% had intraoperative hematoma, which was treated with local compression and antibiotics. One patient (8.3% had residual mucosal prolapse, which was resected. Prolapse recurrence was seen in one case (8.3%. Improved incontinence occurred in 75% of patients and one patient reported obstructed evacuation in the first month after surgery. No death occurred. CONCLUSION: Transanal rectopexy is a simple, low cost technique, which has shown good efficacy in rectal prolapse control.OBJETIVO: O presente estudo analisou os resultados da retopexia pela via transanal e expôs os benefícios desta técnica cirúrgica. MÉTODO: Doze pacientes com prolapso foram operados no período de 1997 a 2011. A técnica cirúrgica usada foi a retopexia transanal, onde o mesorreto foi fixado ao sacro com fio inabsorvível. Três pacientes tinham cirurgia prévia, dois pela técnica de Delorme e um pela técnica de Thiersch. RESULTADOS: A permanência hospitalar pós-operatória variou de 1- 4 dias. Uma paciente (8,3% apresentou hematoma transoperatório que foi tratado com compressão local e antibioticoterapia. Um paciente apresentou prolapso mucoso residual (8,3%, que foi ressecado. Houve recidiva da procidência em um caso (8,3%. A melhora da incontinência ocorreu em 75% dos pacientes e uma paciente apresentou bloqueio evacuatório no primeiro mês após a cirurgia. Não houve mortalidade entre os pacientes operados. CONCLUSÃO: A retopexia transanal é uma t

  2. Soft substrates drive optimal differentiation of human healthy and dystrophic myotubes.

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Reghelin, Elena; Pasut, Alessandra; Cimetta, Elisa; Elvassore, Nicola

    2010-04-01

    The in vitro development of human myotubes carrying genetic diseases, such as Duchenne Muscular Dystrophy, will open new perspectives in the identification of innovative therapeutic strategies. Through the proper design of the substrate, we guided the differentiation of human healthy and dystrophic myoblasts into myotubes exhibiting marked functional differentiation and highly defined sarcomeric organization. A thin film of photo cross-linkable elastic poly-acrylamide hydrogel with physiological-like and tunable mechanical properties (elastic moduli, E: 12, 15, 18 and 21 kPa) was used as substrate. The functionalization of its surface by micro-patterning in parallel lanes (75 microm wide, 100 microm spaced) of three adhesion proteins (laminin, fibronectin and matrigel) was meant to maximize human myoblasts fusion. Myotubes formed onto the hydrogel showed a remarkable sarcomere formation, with the highest percentage (60.0% +/- 3.8) of myotubes exhibiting sarcomeric organization, of myosin heavy chain II and alpha-actinin, after 7 days of culture onto an elastic (15 kPa) hydrogel and a matrigel patterning. In addition, healthy myotubes cultured in these conditions showed a significant membrane-localized dystrophin expression. In this study, the culture substrate has been adapted to human myoblasts differentiation, through an easy and rapid methodology, and has led to the development of in vitro human functional skeletal muscle myotubes useful for clinical purposes and in vitro physiological study, where to carry out a broad range of studies on human muscle physiopathology.

  3. Maximal heart rate does not limit cardiovascular capacity in healthy humans

    DEFF Research Database (Denmark)

    Munch, G D W; Svendsen, J H; Damsgaard, R

    2014-01-01

    In humans, maximal aerobic power (VO2 max ) is associated with a plateau in cardiac output (Q), but the mechanisms regulating the interplay between maximal heart rate (HRmax) and stroke volume (SV) are unclear. To evaluate the effect of tachycardia and elevations in HRmax on cardiovascular function...... and capacity during maximal exercise in healthy humans, 12 young male cyclists performed incremental cycling and one-legged knee-extensor exercise (KEE) to exhaustion with and without right atrial pacing to increase HR. During control cycling, Q and leg blood flow increased up to 85% of maximal workload (WLmax...... and RAP (P exercise, suggesting that HRmax and myocardial work capacity do not limit VO2 max in healthy...

  4. Sleep Stage Dependence of Invariance Characteristics in Fluctuations of Healthy Human Heart Rate

    Science.gov (United States)

    Togo, Fumiharu; Kiyono, Ken; Struzik, Zbigniew R.; Yamamoto, Yoshiharu

    2005-08-01

    The outstanding feature of healthy human heart rate is the robust scale invariance in the non-Gaussian probability density function (PDF), which is preserved not only in a quiescent condition, but also in a dynamic state during waking hours [K. Kiyono et al. Phys. Rev. Lett. 93 (2004)]. Together with 1/f like scaling, this characteristic is a strong indication of far-from-equilibrium, critical-like dynamics of heart rate regulation. Our results suggest that healthy human heart rate departs from a critical state-like operation during sleeping hours, at a rate which is heterogeneous with respect to sleep stages annotated according to traditional techniques. We study specific contributions of sleep stages to the relative departure from criticality through the analysis of sleep stage dependence of the root mean square of multiscale local energy and the multiscale PDF. There is a possibility that the involvement of cortical activity may be important for a critical state-like operation.

  5. Sustainable development in terms of interpreting the human right to a healthy environment

    OpenAIRE

    2012-01-01

    In a context of fundamental human right to a healthy environment should be analyzed and other fundamental rights guaranteed by the constitution on which alone their interpretation in the context of environmental protection is in accordance with the principles of sustainable development of society. And the most important is the right to education because education can be achieved only through public awareness on environmental role in sustainable development. This study aims to explore the role...

  6. Cholinergic enhancement augments magnitude and specificity of visual perceptual learning in healthy humans

    OpenAIRE

    Rokem, Ariel; Michael A Silver

    2010-01-01

    Learning through experience underlies the ability to adapt to novel tasks and unfamiliar environments. However, learning must be regulated so that relevant aspects of the environment are selectively encoded. Acetylcholine (ACh) has been suggested to regulate learning by enhancing the responses of sensory cortical neurons to behaviorally-relevant stimuli [1]. In this study, we increased synaptic levels of ACh in the brains of healthy human subjects with the cholinesterase inhibitor donepezil (...

  7. Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

    OpenAIRE

    Giannini, C.; D. Siliqi; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

    2012-01-01

    Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon res...

  8. Plasma levels of oestriol-17 beta, oestriol and human placental lactogen during bed rest.

    Science.gov (United States)

    Chew, P C; Mok, H; Ratnam, S S

    1976-11-01

    Plasma unconjugated oestradiol-17 beta, total oestriol and human placental lactogen levels were measured in twelve healthy volunteers admitted for bed rest in the last trimester of pregnancy. No significant alteration in levels was observed.

  9. Comparison of pharmacokinetics of two fenofibrate tablet formulations in healthy human subjects.

    Science.gov (United States)

    Chachad, Siddharth S; Gole, Milind; Malhotra, Geena; Naidu, Raghu

    2014-06-01

    Fenofibrate is a serum lipid-lowering agent used as an adjunct to diet in patients with hypercholesterolemia and hypertriglyceridemia. The new fenofibrate tablet formulation was developed as a pharmaceutical equivalent to the marketed tablet formulation containing 145 mg. The objective of this study was to compare the pharmacokinetics and safety of 2 tablet formulations containing 145 mg of fenofibrate (CAS number 49562-28-9) in healthy human subjects. The study was a randomized, 2-treatment, 3-period, 3-sequence, single-dose, 3-way crossover, partial replicate bioequivalence study in healthy human subjects under fasting conditions. Eligible subjects received each treatment in a crossover manner according to the randomization schedule. Replicate dosing was conducted for the reference formulation to determine its intrasubject variability. The predose blood sample was taken within 1 hour before dosing, and serial blood sampling was performed up to 72.0 hours' postdose. The analysis of plasma samples for concentrations of fenofibric acid, the active metabolite of fenofibrate, was conducted by using a validated LC-MS/MS method. Bioequivalence was to be concluded if the 90% CIs as constructed were within the range of 80% to 125% for Cmax, AUC0-t, and AUC0-∞ for fenofibric acid. Subjects were monitored for safety and tolerability throughout the study. 15 healthy human subjects between 18 and 45 years of age and having body mass index between 18.5 and 30 kg/m(2) were recruited into the study. The 90% CIs for the test/reference mean ratios of the ln-transformed pharmacokinetic variables Cmax, AUC0-t, and AUC0-∞ were within the conventional bioequivalence range of 80% to 125%. Both formulations were well tolerated after a single oral dose in these healthy male subjects. Both fenofibrate tablet formulations demonstrated equivalent rates and extent of systemic absorption, and hence were considered bioequivalent. Copyright © 2014 Elsevier HS Journals, Inc. All rights

  10. HIP2: An online database of human plasma proteins from healthy individuals

    Directory of Open Access Journals (Sweden)

    Shen Changyu

    2008-04-01

    Full Text Available Abstract Background With the introduction of increasingly powerful mass spectrometry (MS techniques for clinical research, several recent large-scale MS proteomics studies have sought to characterize the entire human plasma proteome with a general objective for identifying thousands of proteins leaked from tissues in the circulating blood. Understanding the basic constituents, diversity, and variability of the human plasma proteome is essential to the development of sensitive molecular diagnosis and treatment monitoring solutions for future biomedical applications. Biomedical researchers today, however, do not have an integrated online resource in which they can search for plasma proteins collected from different mass spectrometry platforms, experimental protocols, and search software for healthy individuals. The lack of such a resource for comparisons has made it difficult to interpret proteomics profile changes in patients' plasma and to design protein biomarker discovery experiments. Description To aid future protein biomarker studies of disease and health from human plasma, we developed an online database, HIP2 (Healthy Human Individual's Integrated Plasma Proteome. The current version contains 12,787 protein entries linked to 86,831 peptide entries identified using different MS platforms. Conclusion This web-based database will be useful to biomedical researchers involved in biomarker discovery research. This database has been developed to be the comprehensive collection of healthy human plasma proteins, and has protein data captured in a relational database schema built to contain mappings of supporting peptide evidence from several high-quality and high-throughput mass-spectrometry (MS experimental data sets. Users can search for plasma protein/peptide annotations, peptide/protein alignments, and experimental/sample conditions with options for filter-based retrieval to achieve greater analytical power for discovery and validation.

  11. Beyond Sensation Seeking: A Conceptual Framework for Individual Differences in Psychostimulant Drug Effects in Healthy Humans.

    Science.gov (United States)

    White, Tara L

    2017-02-01

    Psychostimulant addiction is an important, relapsing condition for which there is no effective pharmacological treatment. Countering this problem requires an understanding of the specific risk factors that predispose individuals to initial misuse of these drugs. Healthy individuals display marked individual differences in emotional, behavioral and brain responses to low and moderate doses of stimulant drugs. These between-person differences have been most often studied using personality measures of sensation seeking. However, a growing body of work in healthy adults indicates potentially unique sources of variance in these responses that are related to four dissociable personality domains: extraversion, fearlessness, impulsivity and absorption. These four domains are empirically dissociable and can serve as endophenotypic markers of dopamine, norepinephrine and serotonin function in healthy individuals. The relationship between normal variation in these traits and the pharmacological effects of these drugs is here proposed as a framework for better understanding the specific sources of between-person variation in stimulant drug effects on mood, behavior and brain responses in healthy humans.

  12. The feed-back regulation of erythropoietin production in healthy humans

    Energy Technology Data Exchange (ETDEWEB)

    Klausen, T

    1998-10-01

    The proposed oxygen-dependent feed-back loop regulation of EPO (erythropoietin) production is mainly supported by data from studies in animals and cell cultures. The feed-back loop and its dependence on oxygen was therefore challenged by studies in healthy humans: Exposure of humans to different levels of acute and continued altitude hypobaria provided evidence for an oxygen dependence of the EPO response. This response is consistent with the proposed feed-back loop regulation of EPO production; Exposure to continued altitude hypobaria demonstrated that the decline in human EPO production is initiated before an EPO-induced erythopoiesis is detectable, and that this decline is related to a concomitant decrease in the haemoglobin-oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that the feed-back regulation of EPO production during continued hypobaric hypoxia is exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather than by the effects of an EPO-stimulated erythropoiesis; Increased circulating levels of the proinflammatory cytokine IL-6 was found in healthy humans during four days of altitude exposure as compared with sea level. The other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and the increased serum IL-6 did not induce production of c-reactive protein; Comparable circadian variations in human EPO production were shown in sedentary subjects, athletes, and healthy but hypoxaemic subjects. Human EPO production could not be triggered by one hour of high-intensity exercise, whereas longitudinal changes in exercise showed a trend of relation between human EPO production, serum concentration of free testosterone, and indices of body composition. These results have demonstrated and endogenous, probably hormonal, and oxygen-independent regulation of human EPO production, which is at variance with the oxygen dependent feed-back loop regulation of EPO production. Conclusively, the present

  13. A comparison of healthy human and swine articular cartilage dynamic indentation mechanics.

    Science.gov (United States)

    Ronken, S; Arnold, M P; Ardura García, H; Jeger, A; Daniels, A U; Wirz, D

    2012-05-01

    Articular cartilage is a multicomponent, poroviscoelastic tissue with nonlinear mechanical properties vital to its function. A consequent goal of repair or replacement of injured cartilage is to achieve mechanical properties in the repair tissue similar to healthy native cartilage. Since fresh healthy human articular cartilage (HC) is not readily available, we tested whether swine cartilage (SC) could serve as a suitable substitute for mechanical comparisons. To a first approximation, cartilage tissue and surgical substitutes can be evaluated mechanically as viscoelastic materials. Stiffness measurements (dynamic modulus, loss angle) are vital to function and are also a non-destructive means of evaluation. Since viscoelastic material stiffness is strongly strain rate dependent, stiffness was tested under different loading conditions related to function. Stiffness of healthy HC and SC specimens was determined and compared using two non-destructive, mm-scale indentation test modes: fast impact and slow sinusoidal deformation. Deformation resistance (dynamic modulus) and energy handling (loss angle) were determined. For equivalent anatomic locations, there was no difference in dynamic modulus. However, the HC loss angle was ~35% lower in fast impact and ~12% higher in slow sinusoidal mode. Differences seem attributable to age (young SC, older HC) but also to species anatomy and biology. Test mode-related differences in human-swine loss angle support use of multiple function-related test modes. Keeping loss angle differences in mind, swine specimens could serve as a standard of comparison for mechanical evaluation of e.g. engineered cartilage or synthetic repair materials.

  14. 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.

  15. Faecal carriage of Pseudomonas aeruginosa in healthy humans: antimicrobial susceptibility and global genetic lineages.

    Science.gov (United States)

    Estepa, Vanesa; Rojo-Bezares, Beatriz; Torres, Carmen; Sáenz, Yolanda

    2014-07-01

    The aim of this study was to analyse the Pseudomonas aeruginosa faecal carriage rate in 98 healthy humans and to perform the phenotypic and genotypic characterization of recovered isolates. The genetic relatedness among the isolates was analysed by pulsed-field gel electrophoresis and multilocus sequence typing that was compared with worldwide epidemic clones. Pseudomonas aeruginosa was isolated from eight healthy individuals (8.2%), and two of them remained colonized after 5 months (in one case by the same clone). All 10 isolates (one/sample) were susceptible to 14 tested antipseudomonal agents and lacked integron structures. Six pulsed-field gel electrophoresis patterns and six sequence types (ST245, ST253, ST254, ST274, ST663 and the new one, ST1059) were identified among them. Four groups of OprD alterations were detected based on mutations and deletions related to PAO1 reference strain in our carbapenem-susceptible strains. This is the first study focused on P. aeruginosa from faecal samples of healthy humans that provides additional insights into the antimicrobial resistance and genetic diversity of P. aeruginosa. Although the isolates were antimicrobial susceptible, most of the sequence types detected were genetically related to Spanish epidemic clones or globally spread sequence types, such as ST274 and ST253.

  16. Prolonged (9 h) poikilocapnic hypoxia (12% O2) augments cutaneous thermal hyperaemia in healthy humans.

    Science.gov (United States)

    Lawley, Justin S; Oliver, Samuel J; Mullins, Paul G; Macdonald, Jamie H; Moore, Jonathan P

    2014-06-01

    The primary aim of this study was to investigate the effect of systemic poikilocapnic hypoxia on forearm cutaneous thermal hyperaemia. A secondary aim was to examine the relationship between the individual susceptibility to oxygen desaturation and cutaneous vasodilator capacity. Twelve healthy participants (seven male) were exposed to 9 h of normoxia and 12% poikilocapnic hypoxia in a temperature- and humidity-controlled environmental chamber. Skin blood flow was assessed at the ventral forearm using laser Doppler flowmetry combined with rapid local heating. After 6 min at baseline (skin temperature clamped at 33°C), local skin temperature was elevated at a rate of 0.5°C every 5 s up to 42°C to elicit a sensory axon response and then held constant for 30 min to cause a plateau. Skin blood flow was calculated as cutaneous vascular conductance [CVC; in perfusion units/mean arterial blood pressure (APU mmHg(-1))] and expressed in raw format and relative to heating at 44°C in normoxia (%CVC44). During hypoxaemia, vasodilatation was greater during the initial peak (raw, Δ0.35 APU mmHg(-1), P = 0.09; %CVC44, Δ18%, P = 0.05) and the plateau phase (raw, Δ0.55 APU mmHg(-1), P = 0.03; %CVC44, Δ26%, P = 0.02). The rate of rise in cutaneous blood flow during the initial peak was significantly greater during poikilocapnic hypoxia (P < 0.01). We observed a negative relationship between oxygen saturation in poikilocapnic hypoxia and the change in baseline (P = 0.06), initial peak (P = 0.01) and plateau phase of thermal hyperaemia (P = 0.01). Prolonged poikilocapnic hypoxia causes robust increases in CVC during both phases of thermal hyperaemia that are dependent on the oxygen saturation of the individual.

  17. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri;

    2012-01-01

    Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...... the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density...

  18. 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.

  19. Integrated Safety Assessment of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers.

    Science.gov (United States)

    Crooke, Stanley T; Baker, Brenda F; Kwoh, T Jesse; Cheng, Wei; Schulz, Dan J; Xia, Shuting; Salgado, Nelson; Bui, Huynh-Hoa; Hart, Christopher E; Burel, Sebastien A; Younis, Husam S; Geary, Richard S; Henry, Scott P; Bhanot, Sanjay

    2016-10-01

    The common chemical and biological properties of antisense oligonucleotides provide the opportunity to identify and characterize chemical class effects across species. The chemical class that has proven to be the most versatile and best characterized is the 2'-O-methoxyethyl chimeric antisense oligonucleotides. In this report we present an integrated safety assessment of data obtained from controlled dose-ranging studies in nonhuman primates (macaques) and healthy human volunteers for 12 unique 2'-O-methoxyethyl chimeric antisense oligonucleotides. Safety was assessed by the incidence of safety signals in standardized laboratory tests for kidney and liver function, hematology, and complement activation; as well as by the mean test results as a function of dose level over time. At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis. Effects on complement in nonhuman primates were not observed in humans. Nonhuman primates predicted safe doses in humans, but over predicted risk of complement activation and effects on platelets. Although limited to a single chemical class, comparisons from this analysis are considered valid and accurate based on the carefully controlled setting for the specified study populations and within the total exposures studied.

  20. Circulating N-terminal brain natriuretic peptide and cardiac function in response to acute systemic hypoxia in healthy humans

    NARCIS (Netherlands)

    I. Heinonen (Ilkka); M. Luotolahti (Matti); O. Vuolteenaho (Olli); M. Nikinmaa (Mikko); A. Saraste (Antti); J. Hartiala (Jaakko); J. Koskenvuo (Juha); J. Knuuti (Juhani); O. Arjamaa (Olli)

    2014-01-01

    textabstractBackground: As it remains unclear whether hypoxia of cardiomyocytes could trigger the release of brain natriuretic peptide (BNP) in humans, we investigated whether breathing normobaric hypoxic gas mixture increases the circulating NT-proBNP in healthy male subjects.Methods: Ten healthy y

  1. 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.

  2. Deliberate Microbial Infection Research Reveals Limitations to Current Safety Protections of Healthy Human Subjects.

    Science.gov (United States)

    Evers, David L; Fowler, Carol B; Mason, Jeffrey T; Mimnall, Rebecca K

    2015-08-01

    Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician-investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation.

  3. Antibiotic susceptibility profile of bacilli isolated from the skin of healthy humans.

    Science.gov (United States)

    Tarale, Prashant; Gawande, Sonali; Jambhulkar, Vinay

    2015-01-01

    In the present work, twelve bacilli were isolated from four different regions of human skin from Bela population of Nagpur district, India. The isolated bacilli were identified by their morphological, cultural and biochemical characteristics. Seven isolates were Gram negative rods, out of which five were belong to genus Pseudomonas. Three among the five Gram positive isolates were identified as Dermabactor and the remaining two Bacillus. Their antimicrobial susceptibility profile was determined by Kirby-Bauer disc diffusion method. The isolates showed resistance to several currently used broad-spectrum antibiotics. The Dermabactor genus was resistant to vancomycin, although it was earlier reported to be susceptible. Imipenem was found to be the most effective antibiotic for Pseudomonas while nalidixic acid, ampicillin and tetracycline were ineffective. Isolates of Bacillus displayed resistance to the extended spectrum antibiotics cephalosporin and ceftazidime. Imipenem, carbenicillin and ticarcillin were found to be the most effective antibiotics as all the investigated isolates were susceptible to them. Antibiotic resistance may be due to the overuse or misuse of antibiotics during the treatment, or following constant exposure to antibiotic-containing cosmetic formulations.

  4. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    DEFF Research Database (Denmark)

    Huang, T; Larsen, K T; Ried-Larsen, M

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational...

  5. Non extensive Statistic of Tsallis in the heartbeat of healthy humans

    CERN Document Server

    Ritto, P A

    2007-01-01

    It is studied the MIT-BIH Normal Sinus Rhythm Database using a statistical technique of analysis based on the Wavelet and Hilbert Transforms. With that technique, it was previously found, that there is a collective and intrinsic dynamical behavior up to a scale of 64 heartbeats. Now it is shown, that using the Biorthogonal wavelet bior3.1 such a behavior reaches the scale 1024. That result confirms, that the circulatory system is out of equilibrium and that the healthy human being is characterized by a non extensive parameter q=1.7 in the Statistics of Tsallis.

  6. Effects of frontal transcranial direct current stimulation on emotional processing and mood in healthy humans

    Directory of Open Access Journals (Sweden)

    Michael A. Nitsche

    2012-06-01

    Full Text Available The prefrontal cortex is involved in mood and emotional processing. In patients suffering from depression, the left dorsolateral prefrontal cortex is hypoactive, while activity of the right dorsolateral prefrontal cortex is enhanced. Counterbalancing these pathological excitability alterations by repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS improves mood in these patients. In healthy subjects, however, rTMS of the same areas has no major effect, and the effects of tDCS are mixed. We aimed to evaluate the effects of prefrontal tDCS on mood and mood-related cognitive processing in healthy humans. In a first study, we administered excitability-enhancing anodal, excitability-diminishing cathodal and placebo tDCS to the left dorsolateral prefrontal cortex, combined with antagonistic stimulation of the right frontopolar cortex, and tested acute mood changes by an adjective checklist. Subjective mood was not influenced by tDCS. Emotional face identification, however, which was explored in a second experiment, was subtly improved by a tDCS-driven excitability modulation of the prefrontal cortex, markedly by anodal tDCS of the left dorsolateral prefrontal cortex for positive emotional content. We conclude that tDCS of the prefrontal cortex improves mood processing in healthy subjects, but does not influence subjective mood state.

  7. Identification of a novel picornavirus in healthy piglets and seroepidemiological evidence of its presence in humans.

    Directory of Open Access Journals (Sweden)

    Jie-mei Yu

    Full Text Available In this study, we describe a novel porcine parechovirus-like virus (tentatively named PLV-CHN from healthy piglets in China using 454 high-throughput sequencing. The complete genome of the virus comprises 6832 bp, encoding a predicted polyprotein of 2132 amino acids that is most similar to Ljungan virus (32% identity. A similar virus that belongs to a novel Picornaviridae genus, named swine pasivirus 1 (SPaV-1, was reported during the preparation of this paper. Sequence analysis revealed that PLV-CHN and SPaV1 shared 82% nucleotide identity and 89% amino acid identity. Further genomic and phylogenetic analyses suggested that both SPaV1 and PLV-CHN shared similar genomic characteristics and belong to the same novel Picornaviridae genus. A total of 36 (20.0% fecal samples from 180 healthy piglets were positive for PLV-CHN by RT-PCR, while no fecal samples from 100 healthy children and 100 children with diarrhea, and no cerebrospinal fluid samples from 196 children with suspected viral encephalitis, was positive for the virus. However, Western blot and enzyme-linked immunosorbent assays using recombinant PLV-CHN VP1 polypeptide as an antigen showed a high seroprevalence of 63.5% in the healthy population. When grouped by age, the antibody-positivity rates showed that the majority of children under 12 years of age have been infected by the virus. It was suggested that PLV-CHN, SPaV1, or an as-yet-uncharacterized virus can infect humans early in life. Thus, investigation of the role of this novel virus is vital.

  8. Fourier series analysis of the electrophysiological pattern of fatigue in healthy human beings, after curare administration.

    Science.gov (United States)

    Vatine, J J; Shochina, M; Mahler, Y; Gonen, B; Magora, A

    1991-08-01

    Real time computer analysis of the electrophysiological development of muscular fatigue after small doses of d-tubocurarine (TC), has been examined in anesthetized human beings. As compared to a decrease of frequency in the control measurements, previous studies have shown an increase of the frequency of spikes after TC administration. The present experiments were carried out on the biceps brachii of 8 healthy human volunteers maintained in isometric contraction against a constant counter load until complete fatigue occurred. The Fourier spectrum analysis showed a statistically significant shift to lower frequencies before, and a milder statistically non significant shift after TC. These results may indicate that under mild curarization the early phase of muscular contraction requires a higher number of large motor units and thus, at a later stage of the contraction the pool of available large motor units becomes smaller. This conclusion supports the hypothesis that mild curarization causes a state of initial muscular fatigue.

  9. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects

    DEFF Research Database (Denmark)

    Larsen, Steen; Nielsen, Joachim; Neigaard Nielsen, Christina

    2012-01-01

    closely associated these commonly used biochemical measures are to muscle mitochondrial content and muscle oxidative capacity (OXPHOS).Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO(2peak)) and muscle......Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how...... to muscle oxidative capacity followed by complex II activity.We conclude that cardiolipin content, CS and complex I activity are the biomarkers that exhibit the strongest association to mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle....

  10. 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.

  11. Higher prevalence and abundance of Bdellovibrio bacteriovorus in the human gut of healthy subjects.

    Directory of Open Access Journals (Sweden)

    Valerio Iebba

    Full Text Available INTRODUCTION: Members of the human intestinal microbiota are key players in maintaining human health. Alterations in the composition of gut microbial community (dysbiosis have been linked with important human diseases. Understanding the underlying processes that control community structure, including the bacterial interactions within the microbiota itself, is essential. Bdellovibrio bacteriovorus is a gram-negative bacterium that preys other gram-negative species for survival, acting as a population-balancer. It was found in terrestrial/aquatic ecosystems, and in animal intestines, postulating its presence also in the human gut. METHODS: The present study was aimed to evaluate, by end-point PCR and qPCR, the presence of B. bacteriovorus in intestinal and faecal biopsy specimens from 92 paediatric healthy subjects and patients, suffering from Inflammatory Bowel Diseases (IBD, Celiac disease and Cystic fibrosis (CF. RESULTS: i B. bacteriovorus was present and abundant only in healthy individuals, while it was heavily reduced in patients, as in the case of IBD and Celiac, while in CF patients and relative controls we observed comparable results; ii B. bacteriovorus seemed to be mucosa-associated, because all IBD and Celiac biopsies (and related controls were treated with mucus-removing agents, leaving only the mucosa-attached microflora; iii B. bacteriovorus abundance was district-dependent, with a major preponderance in duodenum, and gradually decreasing up to rectum; iv B. bacteriovorus levels significantly dropped in disease status, in duodenum and ileum. CONCLUSIONS: Results obtained in this study could represent the first step for new therapeutic strategies aimed to restore a balance in the intestinal ecosystem, utilizing Bdellovibrio as a probiotic.

  12. Vaccination of healthy subjects and autoantibodies: from mice through dogs to humans.

    Science.gov (United States)

    Toplak, N; Avcin, T

    2009-11-01

    Vaccination against pathogenic microorganisms is one of the major achievements of modern medicine, but due to an increasing number of reports of adverse reactions the vaccination procedure has induced also considerable debate. It is well known that certain infections are involved in triggering the production of autoantibodies, which could lead to autoimmune adverse reactions in genetically predisposed subjects. Based on these findings it was assumed that vaccinations might induce similar autoimmune reactions. At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vaccination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccination-induced autoantibodies in apparently healthy subjects including studies in animals and humans.

  13. Effects of Chinese Liquors on Cardiovascular Disease Risk Factors in Healthy Young Humans

    Directory of Open Access Journals (Sweden)

    Ju-Sheng Zheng

    2012-01-01

    Full Text Available Objectives. To elucidate whether consumption of two Chinese liquors, tea-flavor liquor (TFL and traditional Chinese liquor (TCL have protective effects on cardiovascular disease (CVD risk factors in healthy human subjects. Methods. Forty-five healthy subjects (23 men, 22 women, aged 23–28, were recruited and randomized into two groups: TFL and TCL, and consumed 30 mL/day (45% (v/v alcohol of either liquor for 28 days. Results. Serum high-density lipoprotein cholesterol/low-density lipoprotein cholesterol (HDL-C/LDL-C and apolipoprotein A1 were significantly increased, and total cholesterol (TC and TC/HDL-C were significantly decreased after the intervention in both groups (P<0.05. Serum uric acid (P=0.004 for TFL, P=0.001 for TCL, glucose (P<0.001 for TFL, P<0.001 for TCL and endothelial adhesion molecules (P<0.05 were significantly decreased after the intervention. ADP-induced whole blood platelet aggregation was also significantly decreased after the intervention in both TFL and TCL groups (P<0.05. Conclusions. TFL and TCL consumption had protective effects on CVD risk factors in young humans. However, the results were valid only for 28 days, and that the possibility of adverse effect (liver, kidney of chronic alcohol consumption should be considered.

  14. Visceral response to acute retrograde gastric electrical stimulation in healthy human

    Institute of Scientific and Technical Information of China (English)

    Shu-Kun Yao; Mei-Yun Ke; Zhi-Feng Wang; Da-Bo Xu; Yan-Li Zhang

    2005-01-01

    AIM: To investigate the visceral response to acute retrograde gastric electrical stimulation (RGES) in healthy humans and to derive optimal parameters for treatment of patients with obesity.METHODS: RGES with a series of effective parameters were performed via a bipolar mucosal electrode implanted along the great curvature 5 cm above pylorus of stomach in 12 healthy human subjects. Symptoms associated with dyspepsia and other discomfort were observed and graded during RGES at different settings, including long pulse and pulse train. Gastric myoelectrical activity at baseline and during different settings of stimulation was recorded by a multi-channel electrogastrography.RESULTS: The gastric slow wave was entrained in all the subjects at the pacing parameter of 9 cpm in frequency, 500 ms in pulse width, and 5 mA in amplitude.The frequently appeared symptoms during stimulation were satiety, bloating, discomfort, pain, sting, and nausea. The total symptom score for each subject significantly increased as the amplitude or pulse width was adjusted to a higher scale in both long pulse and pulse train. There was a wide diversity of visceral responses to RGES among individuals.CONCLUSION: Acute RGES can result in a series of symptoms associated with dyspepsia, which is beneficial to the treatment of obesity. Optimal parameter should be determined according to the individual sensitivity to electrical stimulation.

  15. Study of OH● Radicals in Human Serum Blood of Healthy Individuals and Those with Pathological Schizophrenia

    Directory of Open Access Journals (Sweden)

    Wolfgang Linert

    2011-01-01

    Full Text Available The human body is constantly under attack from free radicals that occur as part of normal cell metabolism, and by exposure to environmental factors such as UV light, cigarette smoke, environmental pollutants and gamma radiation. The resulting “Reactive Oxygen Species” (ROS circulate freely in the body with access to all organs and tissues, which can have serious repercussions throughout the body. The body possesses a number of mechanisms both to control the production of ROS and to cope with free radicals in order to limit or repair damage to tissues. Overproduction of ROS or insufficient defense mechanisms leads to a dangerous disbalance in the organism. Thereby several pathomechanisms implicated in over 100 human diseases, e.g., cardiovascular disease, cancer, diabetes mellitus, physiological disease, aging, etc., can be induced. Thus, a detailed investigation on the quantity of oxygen radicals, such as hydroxyl radicals (OH● in human serum blood, and its possible correlation with antioxidant therapy effects, is highly topical. The subject of this study was the influence of schizophrenia on the amount of OH● in human serum blood. The radicals were detected by fluorimetry, using terephthalic acid as a chemical trap. For all experiments the serum blood of healthy people was used as a control group.

  16. Enhancement of Fat Oxidation by Licorice Flavonoid Oil in Healthy Humans during Light Exercise.

    Science.gov (United States)

    Mori, Noriyuki; Nakanishi, Saki; Shiomi, Seiko; Kiyokawa, Shoko; Kakimoto, Sachie; Nakagawa, Kaku; Hosoe, Kazunori; Minami, Kazuhiro; Nadamoto, Tomonori

    2015-01-01

    Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of hydrophobic licorice polyphenols in medium-chain triglycerides. Recent studies reported that LFO prevented and ameliorated diet-induced obesity via the regulation of lipid metabolism-related gene expression in the livers of mice and rats, while it reduced body weight in overweight human subjects by reducing total body fat. However, the direct effects of LFO on energy metabolism have not been studied in human subjects. Therefore, we investigated the effects of ingestion of LFO on energy metabolism, including fat oxidation, by measuring body surface temperature under resting conditions and respiratory gas analysis under exercise conditions in healthy humans. We showed that ingestion of a single 600 mg dose of LFO elevated body trunk skin temperature when measured in a slightly cooled air-conditioned room, and increased oxygen consumption and decreased the respiratory exchange ratio as measured by respiratory gas analysis during 40% Vo2max exercise with a cycle ergometer. Furthermore, repeated ingestion of 300 mg of LFO for 8 d decreased respiratory exchange during the recovery period following 40 min of 30% Vo2max exercise on a treadmill. These results suggest that LFO enhances fat oxidation in humans during light exercise.

  17. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    Science.gov (United States)

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.

  18. Prevalence of human enteroviruses among apparently healthy nursery school children in Accra.

    Science.gov (United States)

    Attoh, Juliana; Obodai, Evangeline; Adiku, Theophilus; Odoom, John Kofi

    2014-01-01

    Human enteroviruses are common in children causing asymptomatic infections ranging from mild to severe illnesses. In Ghana, information on the prevalence of non-polio enterovirus causing acute flaccid paralysis is available but data on surveillance of these viruses in school children is scanty. Here, the prevalence of human enteroviruses among apparently healthy children in selected school in Accra was studied. Stool samples from 273 apparently healthy children less than eight years of age in 9 selected nursery schools were collected between December 2010 and March 2011 and processed for human enteroviruses on L20B, RD and Hep-2 cell lines. Positive Isolates were characterized by microneutralisation assay with antisera pools from RIVM, the Netherlands according to standard methods recommended by WHO. Of the 273 samples processed, 66 (24.2%) non-polio enteroviruses were isolated. More growth was seen on Hep-2C (46%) only than RD (18%) only and on both cell lines (34%). No growth was seen on L20B even after blind passage. Excretion of non-polio enteroviruses was found in all the schools with majority in BD school. Serotyping of the isolates yielded predominantly Coxsackie B viruses followed by echoviruses 13 and 7. More than half of the isolates could not be typed by the antisera pools. The study detected 13 different serotypes of non-polio enteroviruses in circulation but no poliovirus was found. BD school was found to have the highest prevalence of NPEV. Complete identification through molecular methods is essential to establish the full range of NPEVs in circulation in these schools.

  19. Antiaging effects of the mixture of Panax ginseng and Crataegus pinnatifida in human dermal fibroblasts and healthy human skin.

    Science.gov (United States)

    Hwang, Eunson; Park, Sang-Yong; Yin, Chang Shik; Kim, Hee-Taek; Kim, Yong Min; Yi, Tae Hoo

    2017-01-01

    Human skin undergoes distinct changes throughout the aging process, based on both intrinsic and extrinsic factors. In a process called photoaging, UVB irradiation leads to upregulation of matrix metalloproteinase-1, which then causes collagen degradation and premature aging. Mixtures of medicinal plants have traditionally been used as drugs in oriental medicine. Based on the previously reported antioxidant properties of Panax ginseng Meyer and Crataegus pinnatifida, we hypothesized that the mixture of P. ginseng Meyer and C. pinnatifida (GC) would have protective effects against skin aging. Anti-aging activity was examined both in human dermal fibroblasts under UVB irradiation by using Western blot analysis and in healthy human skin by examining noninvasive measurements. In vitro studies showed that GC improved procollagen type I expression and diminished matrix metalloproteinase-1 secretion. Based on noninvasive measurements, skin roughness values, including total roughness (R1), maximum roughness (R2), smoothness depth and average roughness (R3), and global photodamage scores were improved by GC application. Moreover, GC ameliorated the high values of smoothness depth (R4), which means that GC reduced loss of skin moisture. These results suggest that GC can prevent aging by inhibiting wrinkle formation and increasing moisture in the human skin.

  20. Gene Sequence Analyses of the Healthy Oral Microbiome in Humans and Companion Animals.

    Science.gov (United States)

    Davis, Eric M

    2016-06-01

    It has long been accepted that certain oral bacterial species are responsible for the development of periodontal disease. However, the focus of microbial and immunological research is shifting from studying the organisms associated with disease to examining the indigenous microbial inhabitants that are present in health. Microbiome refers to the aggregate genetic material of all microorganisms living in, or on, a defined habitat. Recent developments in gene sequence analysis have enabled detection and identification of bacteria from polymicrobial samples, including subgingival plaque. Diversity surveys utilizing this technology have demonstrated that bacterial culture techniques have vastly underestimated the richness and diversity of microorganisms in vivo, since only certain bacteria grow in vitro. Surveys using gene sequence analysis have demonstrated that the healthy oral microbiome is composed of an unexpectedly high number of diverse species, including putative pathogens. These findings support the view that coevolution microorganisms and macroscopic hosts has occurred in which certain microorganisms have adapted to survive in the oral cavity and host immune tolerance has allowed the establishment of a symbiotic relationship in which both parties receive benefits (mutualism). This review describes gene sequence analysis as an increasingly common, culture-independent tool for detecting bacteria in vivo and describes the results of recent oral microbiome diversity surveys of clinically healthy humans, dogs, and cats. Six bacterial phyla consistently dominated the healthy oral microbiome of all 3 host species. Previous hypotheses on etiology of periodontitis are reviewed in light of new scientific findings. Finally, the consideration that clinically relevant periodontal disease occurs when immune tolerance of the symbiotic oral microbiome is altered to a proinflammatory response will be discussed.

  1. Expiratory muscle loading increases intercostal muscle blood flow during leg exercise in healthy humans

    Science.gov (United States)

    Athanasopoulos, Dimitris; Louvaris, Zafeiris; Cherouveim, Evgenia; Andrianopoulos, Vasilis; Roussos, Charis; Zakynthinos, Spyros

    2010-01-01

    We investigated whether expiratory muscle loading induced by the application of expiratory flow limitation (EFL) during exercise in healthy subjects causes a reduction in quadriceps muscle blood flow in favor of the blood flow to the intercostal muscles. We hypothesized that, during exercise with EFL quadriceps muscle blood flow would be reduced, whereas intercostal muscle blood flow would be increased compared with exercise without EFL. We initially performed an incremental exercise test on eight healthy male subjects with a Starling resistor in the expiratory line limiting expiratory flow to ∼ 1 l/s to determine peak EFL exercise workload. On a different day, two constant-load exercise trials were performed in a balanced ordering sequence, during which subjects exercised with or without EFL at peak EFL exercise workload for 6 min. Intercostal (probe over the 7th intercostal space) and vastus lateralis muscle blood flow index (BFI) was calculated by near-infrared spectroscopy using indocyanine green, whereas cardiac output (CO) was measured by an impedance cardiography technique. At exercise termination, CO and stroke volume were not significantly different during exercise, with or without EFL (CO: 16.5 vs. 15.2 l/min, stroke volume: 104 vs. 107 ml/beat). Quadriceps muscle BFI during exercise with EFL (5.4 nM/s) was significantly (P = 0.043) lower compared with exercise without EFL (7.6 nM/s), whereas intercostal muscle BFI during exercise with EFL (3.5 nM/s) was significantly (P = 0.021) greater compared with that recorded during control exercise (0.4 nM/s). In conclusion, increased respiratory muscle loading during exercise in healthy humans causes an increase in blood flow to the intercostal muscles and a concomitant decrease in quadriceps muscle blood flow. PMID:20507965

  2. Mythematics Solving the Twelve Labors of Hercules

    CERN Document Server

    Huber, Michael

    2009-01-01

    How might Hercules, the most famous of the Greek heroes, have used mathematics to complete his astonishing Twelve Labors? From conquering the Nemean Lion and cleaning out the Augean Stables, to capturing the Erymanthean Boar and entering the Underworld to defeat the three-headed dog Cerberus, Hercules and his legend are the inspiration for this book of fun and original math puzzles. While Hercules relied on superhuman strength to accomplish the Twelve Labors, Mythematics shows how math could have helped during his quest. How does Hercules defeat the Lernean Hydra and stop its heads from multip

  3. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Jersie-Christensen, Rosa R; Lyon, David

    2016-01-01

    BACKGROUND: The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients...... with periodontitis and dental caries to healthy individuals. METHODS: Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically...... spectrometer operated in data-dependent acquisition mode. RESULTS: We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system...

  4. Prebiotic effects of almonds and almond skins on intestinal microbiota in healthy adult humans.

    Science.gov (United States)

    Liu, Zhibin; Lin, Xiuchun; Huang, Guangwei; Zhang, Wen; Rao, Pingfan; Ni, Li

    2014-04-01

    Almonds and almond skins are rich in fiber and other components that have potential prebiotic properties. In this study we investigated the prebiotic effects of almond and almond skin intake in healthy humans. A total of 48 healthy adult volunteers consumed a daily dose of roasted almonds (56 g), almond skins (10 g), or commercial fructooligosaccharides (8 g) (as positive control) for 6 weeks. Fecal samples were collected at defined time points and analyzed for microbiota composition and selected indicators of microbial activity. Different strains of intestinal bacteria had varying degrees of growth sensitivity to almonds or almond skins. Significant increases in the populations of Bifidobacterium spp. and Lactobacillus spp. were observed in fecal samples as a consequence of almond or almond skin supplementation. However, the populations of Escherichia coli did not change significantly, while the growth of the pathogen Clostridum perfringens was significantly repressed. Modification of the intestinal microbiota composition induced changes in bacterial enzyme activities, specifically a significant increase in fecal β-galactosidase activity and decreases in fecal β-glucuronidase, nitroreductase and azoreductase activities. Our observations suggest that almond and almond skin ingestion may lead to an improvement in the intestinal microbiota profile and a modification of the intestinal bacterial activities, which would induce the promotion of health beneficial factors and the inhibition of harmful factors. Thus we believe that almonds and almond skins possess potential prebiotic properties.

  5. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

    Science.gov (United States)

    Lippelt, D P; van der Kint, S; van Herk, K; Naber, M

    2016-01-01

    Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

  6. TH17, TH22 and Treg cells are enriched in the healthy human cecum.

    Directory of Open Access Journals (Sweden)

    Martin J Wolff

    Full Text Available There is increasing evidence that dysregulation of CD4(+ T cell populations leads to intestinal inflammation, but the regional distribution of these populations throughout the intestinal tract in healthy individuals remains unclear. Here, we show that T(H17, T(H22 and T(Reg cells are enriched in the healthy human cecum compared to the terminal ileum and sigmoid colon, whereas T(H1 and T(H2 cells do not significantly vary by location. Transcriptional profiling analysis of paired pinch biopsies from different regions of the intestine identified significant differences in the metabolic state of the terminal ileum, cecum, and sigmoid colon. An increased proportion of T(H17 cells was positively associated with expression of resistin (RETN and negatively associated with expression of trefoil factor 1 (TFF1. These results suggest that CD4(+ T helper cells that are important in maintaining mucosal barrier function may be enriched in the cecum as a result of metabolic differences of the surrounding microenvironment.

  7. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

    Directory of Open Access Journals (Sweden)

    D P Lippelt

    Full Text Available Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

  8. Post-prandial rise of microvesicles in peripheral blood of healthy human donors.

    Science.gov (United States)

    Suštar, Vid; Bedina-Zavec, Apolonija; Stukelj, Roman; Frank, Mojca; Ogorevc, Eva; Janša, Rado; Mam, Keriya; Veranič, Peter; Kralj-Iglič, Veronika

    2011-03-21

    Microvesicles isolated from body fluids are membrane - enclosed fragments of cell interior which carry information on the status of the organism. It is yet unclear how metabolism affects the number and composition of microvesicles in isolates from the peripheral blood. To study the post - prandial effect on microvesicles in isolates from the peripheral blood of 21 healthy donors, in relation to blood cholesterol and blood glucose concentrations. The average number of microvesicles in the isolates increased 5 hours post - prandially by 52%; the increase was statistically significant (p = 0.01) with the power P = 0.68, while the average total blood cholesterol concentration, average low density lipoprotein cholesterol concentration (LDL-C) and average high density lipoprotein cholesterol concentration (HDL-C) all remained within 2% of their fasting values. We found an 11% increase in triglycerides (p = 0.12) and a 6% decrease in blood glucose (p microvesicles negatively correlated with the post - fasting total cholesterol concentration (r = - 0.46, p = 0.035) while the difference in the number of microvesicles in the isolates between post - prandial and post - fasting states negatively correlated with the respective difference in blood glucose concentration (r = - 0.39, p = 0.05). In a population of healthy human subjects the number of microvesicles in isolates from peripheral blood increased in the post - prandial state. The increase in the number of microvesicles was affected by the fasting concentration of cholesterol and correlated with the decrease in blood glucose.

  9. Heart rate variability, overnight urinary norepinephrine, and plasma cholesterol in apparently healthy human adults.

    Science.gov (United States)

    Thayer, Julian F; Fischer, Joachim E

    2013-01-20

    The aim of this study was to assess the relationship between autonomic nervous system activity as indexed by measures of heart rate variability and overnight urinary norepinephrine, and plasma cholesterol levels in a large sample of working adults. The study population comprised 611 apparently healthy employees of an airplane manufacturing plant in Southern Germany. Heart rate variability was calculated as beat-to-beat intervals over the course of one 24-hour weekday measured with an ambulatory ECG recorder. Overnight urine collection and blood samples were also obtained. We found an inverse association between indices of vagally-mediated heart rate variability and plasma levels of total cholesterol, low density lipoprotein (LDL), and the ratio of LDL to high density lipoprotein (HDL) that remained significant in multivariate models after controlling for relevant covariates including norepinephrine. Urinary norepinephrine was not significantly related to any measure of cholesterol in multivariate models. We report here for the first time, in a large sample of healthy human adults, evidence supporting the hypothesis of a clinically relevant inverse relationship between measures of plasma cholesterol and vagally-mediated heart rate variability after controlling for sympathetic nervous system activity. This suggests an important role for the vagal control of plasma cholesterol levels in cardiovascular disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction.

    Science.gov (United States)

    Bakun, M; Senatorski, G; Rubel, T; Lukasik, A; Zielenkiewicz, P; Dadlez, M; Paczek, L

    2014-02-01

    Aging is a complex physiological process that poses considerable conundrums to rapidly aging societies. For example, the risk of dying from cardiovascular diseases and/or cancer steadily declines for people after their 60s, and other causes of death predominate for seniors older than 80 years of age. Thus, physiological aging presents numerous unanswered questions, particularly with regard to changing metabolic patterns. Urine proteomics analysis is becoming a non-invasive and reproducible diagnostic method. We investigated the urine proteomes in healthy elderly people to determine which metabolic processes were weakened or strengthened in aging humans. Urine samples from 37 healthy volunteers aged 19-90 years (19 men, 18 women) were analyzed for protein expression by liquid chromatography-tandem mass spectrometry. This generated a list of 19 proteins that were differentially expressed in different age groups (young, intermediate, and old age). In particular, the oldest group showed protein changes reflective of altered extracellular matrix turnover and declining immune function, in which changes corresponded to reported changes in cardiovascular tissue remodeling and immune disorders in the elderly. Thus, urinary proteome changes in the elderly appear to reflect the physiological processes of aging and are particularly clearly represented in the circulatory and immune systems. Detailed identification of "protein trails" creates a more global picture of metabolic changes that occur in the elderly.

  11. Characterization of the fungal microbiota (mycobiome in healthy and dandruff-afflicted human scalps.

    Directory of Open Access Journals (Sweden)

    Hee Kuk Park

    Full Text Available The human scalp harbors a vast community of microbial mutualists, the composition of which is difficult to elucidate as many of the microorganisms are not culturable using current culture techniques. Dandruff, a common scalp disorder, is known as a causative factor of a mild seborrheic dermatitis as well as pityriasis versicolor, seborrheic dermatitis, and atopic dermatitis. Lipophilic yeast Malassezia is widely accepted to play a role in dandruff, but relatively few comprehensive studies have been reported. In order to investigate fungal biota and genetic resources of dandruff, we amplified the 26S rRNA gene from samples of healthy scalps and dandruff-afflicted scalps. The sequences were analyzed by a high throughput method using a GS-FLX 454 pyrosequencer. Of the 74,811 total sequence reads, Basidiomycota (Filobasidium spp. was the most common phylum associated with dandruff. In contrast, Ascomycota (Acremonium spp. was common in the healthy scalps. Our results elucidate the distribution of fungal communities associated with dandruff and provide new avenues for the potential prevention and treatment of dandruff.

  12. Synchrotron X-ray diffraction characterization of healthy and fluorotic human dental enamel

    Science.gov (United States)

    Colaço, M. V.; Barroso, R. C.; Porto, I. M.; Gerlach, R. F.; Costa, F. N.; Braz, D.; Droppa, R.; de Sousa, F. B.

    2012-10-01

    With the introduction of fluoride as the main anticaries agent used in preventive dentistry, and perhaps an increase in fluoride in our food chain, dental fluorosis has become an increasing world-wide problem. Visible signs of fluorosis begin to become obvious on the enamel surface as opacities, implying some porosity in the tissue. The mechanisms that conduct the formation of fluorotic enamel are unknown, but should involve modifications in the basic physical-chemistry reactions of demineralization and remineralisation of the enamel of the teeth, which is the same reaction of formation of the enamel's hydroxyapatite (HAp) in the maturation phase. The increase of the amount of fluoride inside of the apatite will result in gradual increase of the lattice parameters. The aim of this work is to characterize the healthy and fluorotic enamel in human tooth using Synchrotron X-ray diffraction. All the scattering profile measurements were carried out at the X-ray diffraction beamline (XRD1) at the Brazilian Synchrotron Light Laboratory—LNLS, Campinas, Brazil. X-ray diffraction experiments were performed both in powder samples and polished surfaces. The powder samples were analyzed to obtain the characterization of a typical healthy enamel pattern. The polished surfaces were analyzed in specific areas that have been identified as fluorotic ones. X-ray diffraction data were obtained for all samples and these data were compared with the control samples and also with the literature data.

  13. A Simple Predictive Method of Critical Flicker Detection for Human Healthy Precaution

    Directory of Open Access Journals (Sweden)

    Goh Zai Peng

    2015-01-01

    Full Text Available Interharmonics and flickers have an interrelationship between each other. Based on International Electrotechnical Commission (IEC flicker standard, the critical flicker frequency for a human eye is located at 8.8 Hz. Additionally, eye strains, headaches, and in the worst case seizures may happen due to the critical flicker. Therefore, this paper introduces a worthwhile research gap on the investigation of interrelationship between the amplitudes of the interharmonics and the critical flicker for 50 Hz power system. Consequently, the significant findings obtained in this paper are the amplitudes of two particular interharmonics are able to detect the critical flicker. In this paper, the aforementioned amplitudes are detected by adaptive linear neuron (ADALINE. After that, the critical flicker is detected by substituting the aforesaid amplitudes to the formulas that have been generated in this paper accordingly. Simulation and experimental works are conducted and the accuracy of the proposed algorithm which utilizes ADALINE is similar, as compared to typical Fluke power analyzer. In a nutshell, this simple predictive method for critical flicker detection has strong potential to be applied in any human crowded places (such as offices, shopping complexes, and stadiums for human healthy precaution purpose due to its simplicity.

  14. Effects of lipopolysaccharide infusion on arterial levels and transcerebral exchange kinetics of glutamate and glycine in healthy humans

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Taudorf, Sarah; Bailey, Damian M

    2012-01-01

    . Cerebral blood flow (CBF) and arterial to jugular venous concentration differences of glutamate and glycine were determined before and after a 4-h intravenous infusion of Escherichia coli lipopolysaccharide (LPS, total dose of 0.3 ng/kg) in 12 healthy volunteers. The global cerebral net exchange......, their transcerebral exchange kinetics were unaffected. Inflammation-induced alterations of the circulating levels of glutamate and glycine, do not affect the global transcerebral exchange kinetics of these amino acids in healthy humans....

  15. Effect of Tamarindus indica. L on the bioavailability of ibuprofen in healthy human volunteers.

    Science.gov (United States)

    Garba, M; Yakasai, I A; Bakare, M T; Munir, H Y

    2003-01-01

    The influence of Tamarindus indica L fruit extract incorporated in a traditional meal on the bioavailability of Ibuprofen tablets 400 mg dose when given concurrently was studied in 6 healthy human volunteers. There was a statistically significant increase in the plasma levels of Ibuprofen and its metabolites hydroxy-ibuprofen and carboxy-ibuprofen respectively, when the meal containing Tamarindus indica fruit extract was administered with the ibuprofen tablets than when taken under fasting state or with the meal without the fruit extract. The C(max), AUC(0-6 hr) and Ka for ibuprofen increased from 38 +/- 0.70 microg/ml to 42 +/- 0.98 microg/ml (p > 0.05); and 28.03 +/- 2.40 microg/ml x hr to 56.51 +/- 0.16 microg/ml x hr (p Tamarindus indica L. fruit extract significantly increased the bioavailability of Ibuprofen.

  16. Quantification of MRI measured myocardial perfusion reserve in healthy humans: A comparison with positron emission tomography

    DEFF Research Database (Denmark)

    Fritz-Hansen, T.; Hove, J.D.; Kofoed, K.F.;

    2008-01-01

    and during stress induced by dipyridamole in order to determine the myocardial perfusion reserve. Myocardial and blood time concentration curves obtained by Gd-DTPA-enhanced MRI and N-13-ammonia PET were fitted by a two-compartment perfusion model. Results: Mean perfusion values (+/- SD) derived from the MRI......Purpose: To validate a noninvasive quantitative MRI technique, the K-i perfusion method, for myocardial perfusion in humans using N-13-ammonia PET as a reference method. Materials and Methods: Ten healthy males (64 +/- 8 years) were examined with combined PET and MRI perfusion imaging at rest...... method at rest and at hyperemia were 80 +/- 20 and 183 +/- 56 mL/min/100 g, respectively. The same data for PET were 71 +/- 16 and 203 +/- 67 mL/min/100 g. A linear relationship was observed between MRI and PET-derived myocardial perfusion reserve for regional and global data. Linear regression...

  17. Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

    Science.gov (United States)

    Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

    2013-12-01

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

  18. A 3D map of the islet routes throughout the healthy human pancreas

    Science.gov (United States)

    Ionescu-Tirgoviste, Constantin; Gagniuc, Paul A.; Gubceac, Elvira; Mardare, Liliana; Popescu, Irinel; Dima, Simona; Militaru, Manuella

    2015-01-01

    Islets of Langerhans are fundamental in understanding diabetes. A healthy human pancreas from a donor has been used to asses various islet parameters and their three-dimensional distribution. Here we show that islets are spread gradually from the head up to the tail section of the pancreas in the form of contracted or dilated islet routes. We also report a particular anatomical structure, namely the cluster of islets. Our observations revealed a total of 11 islet clusters which comprise of small islets that surround large blood vessels. Additional observations in the peripancreatic adipose tissue have shown lymphoid-like nodes and blood vessels captured in a local inflammatory process. Our observations are based on regional slice maps of the pancreas, comprising of 5,423 islets. We also devised an index of sphericity which briefly indicates various islet shapes that are dominant throughout the pancreas. PMID:26417671

  19. The self-care motivation model: theory and practice in healthy human development.

    Science.gov (United States)

    Horowitz, L G

    1985-02-01

    Effective health education and behavior motivation programs are needed to promote the compliance of children and young adults with preventive health care practices. Health promotion and primary prevention programs must consider the entire individual as well as his or her environment if positive behavior changes are to be maintained. This paper introduces an innovative model for self-care motivation curriculum development. The model prescribes the use of value clarification, enhanced physical/cognitive/affective awareness, positive lifestyle choices, and self-reinforcement skills training whereby individuals learn to become self-motivated and reinforcing agents for their own primary preventive health practices. It is theorized that by developing self-care and self-regulation skills, students will achieve and maintain higher levels of wellness, thus improving the quality of their lives and ensuring healthy human development.

  20. Physical exercise habits correlate with gray matter volume of the hippocampus in healthy adult humans.

    Science.gov (United States)

    Killgore, William D S; Olson, Elizabeth A; Weber, Mareen

    2013-12-12

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

  1. Oxidatively damaged DNA and its repair after experimental exposure to wood smoke in healthy humans

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Bräuner, Elvira Vaclavik; Barregard, Lars

    2008-01-01

    Particulate matter from wood smoke may cause health effects through generation of oxidative stress with resulting damage to DNA. We investigated oxidatively damaged DNA and related repair capacity in peripheral blood mononuclear cells (PBMC) and measured the urinary excretion of repair products...... after controlled short-term exposure of human volunteers to wood smoke. Thirteen healthy adults were exposed first to clean air and then to wood smoke in a chamber during 4h sessions, 1 week apart. Blood samples were taken 3h after exposure and on the following morning, and urine was collected after...... chromatography with mass spectrometry. The morning following exposure to wood smoke the PBMC levels of SB were significantly decreased and the mRNA levels of hOGG1 significantly increased. FPG sites, hOGG1 activity, expression of hNUDT1 and hHO1, urinary excretion of 8-oxodG and 8-oxoGua did not change...

  2. 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.

  3. Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome.

    Science.gov (United States)

    Kishi, Akifumi; Struzik, Zbigniew R; Natelson, Benjamin H; Togo, Fumiharu; Yamamoto, Yoshiharu

    2008-06-01

    Physiological and/or pathological implications of the dynamics of sleep stage transitions have not, to date, been investigated. We report detailed duration and transition statistics between sleep stages in healthy subjects and in others with chronic fatigue syndrome (CFS); in addition, we also compare our data with previously published results for rats. Twenty-two healthy females and 22 female patients with CFS, characterized by complaints of unrefreshing sleep, underwent one night of polysomnographic recording. We find that duration of deep sleep (stages III and IV) follows a power-law probability distribution function; in contrast, stage II sleep durations follow a stretched exponential and stage I, and REM sleep durations follow an exponential function. These stage duration distributions show a gradually increasing departure from the exponential form with increasing depth of sleep toward a power-law type distribution for deep sleep, suggesting increasing complexity of regulation of deeper sleep stages. We also find a substantial number of REM to non-REM sleep transitions in humans, while this transition is reported to be virtually nonexistent in rats. The relative frequency of this REM to non-REM sleep transition is significantly lower in CFS patients than in controls, resulting in a significantly greater relative transition frequency of moving from both REM and stage I sleep to awake. Such an alteration in the transition pattern suggests that the normal continuation of sleep in light or REM sleep is disrupted in CFS. We conclude that dynamic transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with pathophysiological implications.

  4. Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans

    Science.gov (United States)

    Xiao, Changting; Pavlic, Mirjana; Szeto, Linda; Patterson, Bruce W.; Lewis, Gary F.

    2011-01-01

    OBJECTIVE The metabolism of hepatic- and intestinally derived lipoproteins is regulated in a complex fashion by nutrients, hormones, and neurologic and other factors. Recent studies in animal models suggest an important role for glucagon acting via the glucagon receptor in regulating hepatic triglyceride (TG) secretion. Here we examined the direct effects of glucagon on regulation of hepatic and intestinal lipoprotein metabolism in humans. RESEARCH DESIGN AND METHODS Eight healthy men underwent two studies each, in random order, 4–6 weeks apart in which de novo lipogenesis, kinetics of larger VLDL1 TG, and kinetics of VLDL1 and smaller VLDL2 apolipoprotein (apo)B100 and B48 were studied using established stable isotope enrichment methods. Subjects were studied in the constant fed state under conditions of a pancreatic clamp (with infusion of somatostatin, insulin, and growth hormone) at either basal glucagon (BG study, 64.5 ± 2.1 pg/mL) or hyperglucagonemia (high glucagon [HG] study, 183.2 ± 5.1 pg/mL). RESULTS There were no significant differences in plasma concentration of VLDL1 or VLDL2 TG, apoB100 or apoB48 between BG and HG studies. There was, however, lower (P lipoprotein metabolism. CONCLUSIONS Glucagon acutely regulates hepatic but not intestinal lipoprotein particle metabolism in humans both by decreasing hepatic lipoprotein particle production as well as by inhibiting particle clearance, with no net effect on particle concentration. PMID:20980459

  5. Increasing cognitive load attenuates right arm swing in healthy human walking

    Science.gov (United States)

    Killeen, Tim; Easthope, Christopher S.; Filli, Linard; Lőrincz, Lilla; Schrafl-Altermatt, Miriam; Brugger, Peter; Linnebank, Michael; Curt, Armin; Zörner, Björn; Bolliger, Marc

    2017-01-01

    Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

  6. Effect of generalised sympathetic activation by cold pressor test on cerebral haemodynamics in healthy humans.

    Science.gov (United States)

    Roatta, S; Micieli, G; Bosone, D; Losano, G; Bini, R; Cavallini, A; Passatore, M

    1998-07-15

    There is no general agreement regarding several aspects of the role of the sympathetic system on cerebral haemodynamics such as extent of effectiveness, operational range and site of action. This study was planned to identify the effect of a generalised sympathetic activation on the cerebral haemodynamics in healthy humans before it is masked by secondary corrections, metabolic or myogenic in nature. A total of 35 healthy volunteers aged 20-35 underwent a 5 min lasting cold pressor test (CPT) performed on their left hand. The cerebral blood flow (CBF) velocity in the middle cerebral arteries and arterial blood pressure were recorded with transcranial Doppler sonography and with a non-invasive finger-cuff method, respectively. The ratio of arterial blood pressure to mean blood velocity (ABP/Vm) and Pulsatility Index (PI) were calculated throughout each trial. CPT induced an increase in mean ABP (range 2-54 mmHg depending on the subject) and only a slight, though significant, increase in blood velocity in the middle cerebral artery (+2.4 and +4.4% on ipsi- and contralateral side, respectively). During CPT, the ratio ABP/Vm increased and PI decreased in all subjects on both sides. These changes began simultaneously with the increase in blood pressure. The increase in ABP/Vm ratio is attributed to an increase in the cerebrovascular resistance, while the concomitant reduction in PI is interpreted as due to the reduction in the compliance of the middle cerebral artery. The results suggest that generalised increases in the sympathetic discharge, causing increases in ABP, can prevent concomitant increases in CBF by acting on both small resistance and large compliant vessels. This effect is also present when a slight increase in blood pressure occurs, which suggests a moderate increase in the sympathetic discharge, i.e. when ABP remains far below the upper limit of CBF autoregulation.

  7. Effects of methamphetamine administration on information gathering during probabilistic reasoning in healthy humans.

    Directory of Open Access Journals (Sweden)

    Anna O Ermakova

    Full Text Available Jumping to conclusions (JTC during probabilistic reasoning is a cognitive bias repeatedly demonstrated in people with schizophrenia and shown to be associated with delusions. Little is known about the neurochemical basis of probabilistic reasoning. We tested the hypothesis that catecholamines influence data gathering and probabilistic reasoning by administering intravenous methamphetamine, which is known to cause synaptic release of the catecholamines noradrenaline and dopamine, to healthy humans whilst they undertook a probabilistic inference task. Our study used a randomised, double-blind, cross-over design. Seventeen healthy volunteers on three visits were administered either placebo or methamphetamine or methamphetamine preceded by amisulpride. In all three conditions participants performed the "beads" task in which participants decide how much information to gather before making a probabilistic inference, and which measures the cognitive bias towards jumping to conclusions. Psychotic symptoms triggered by methamphetamine were assessed using Comprehensive Assessment of At-Risk Mental States (CAARMS. Methamphetamine induced mild psychotic symptoms, but there was no effect of drug administration on the number of draws to decision (DTD on the beads task. DTD was a stable trait that was highly correlated within subjects across visits (intra-class correlation coefficients of 0.86 and 0.91 on two versions of the task. The less information was sampled in the placebo condition, the more psychotic-like symptoms the person had after the methamphetamine plus amisulpride condition (p = 0.028. Our results suggest that information gathering during probabilistic reasoning is a stable trait, not easily modified by dopaminergic or noradrenergic modulation.

  8. Effects of methamphetamine administration on information gathering during probabilistic reasoning in healthy humans.

    Science.gov (United States)

    Ermakova, Anna O; Ramachandra, Pranathi; Corlett, Philip R; Fletcher, Paul C; Murray, Graham K

    2014-01-01

    Jumping to conclusions (JTC) during probabilistic reasoning is a cognitive bias repeatedly demonstrated in people with schizophrenia and shown to be associated with delusions. Little is known about the neurochemical basis of probabilistic reasoning. We tested the hypothesis that catecholamines influence data gathering and probabilistic reasoning by administering intravenous methamphetamine, which is known to cause synaptic release of the catecholamines noradrenaline and dopamine, to healthy humans whilst they undertook a probabilistic inference task. Our study used a randomised, double-blind, cross-over design. Seventeen healthy volunteers on three visits were administered either placebo or methamphetamine or methamphetamine preceded by amisulpride. In all three conditions participants performed the "beads" task in which participants decide how much information to gather before making a probabilistic inference, and which measures the cognitive bias towards jumping to conclusions. Psychotic symptoms triggered by methamphetamine were assessed using Comprehensive Assessment of At-Risk Mental States (CAARMS). Methamphetamine induced mild psychotic symptoms, but there was no effect of drug administration on the number of draws to decision (DTD) on the beads task. DTD was a stable trait that was highly correlated within subjects across visits (intra-class correlation coefficients of 0.86 and 0.91 on two versions of the task). The less information was sampled in the placebo condition, the more psychotic-like symptoms the person had after the methamphetamine plus amisulpride condition (p = 0.028). Our results suggest that information gathering during probabilistic reasoning is a stable trait, not easily modified by dopaminergic or noradrenergic modulation.

  9. Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Víctor Casanova

    Full Text Available ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID. ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA-mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-α, CXCL8(IL-8, CCL3(MIP1-α, CCL4(MIP-1β and CCL5(RANTES cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.

  10. Observations on pulpal response to carbon dioxide laser drilling of dentine in healthy human third molars.

    Science.gov (United States)

    Nair, P N R; Baltensperger, M; Luder, H U; Eyrich, G K H

    2005-01-01

    Preservation of pulpal health is the primary prerequisite for successful application of laser systems in the hard tissue management of vital teeth. The purpose of this study was to investigate the short and long-term pulpal effects to cavity preparations in healthy human teeth using carbon dioxide (CO2) laser. A total of seven, healthy, third molars that were scheduled to be removed due to space problems were used. After the laser drilling, the occlusal cavities were closed temporarily, and the teeth were extracted 7 days (n=5) and 3 months (n=2) after the operation. The specimens were fixed, decalcified, subdivided and processed for light and transmission electron microscopy. Seven days postoperatively all the five teeth that had been irradiated with the CO2 laser did not reveal any pathological changes in the pulpo-dentine complex. Three months postoperatively the two teeth that were prepared with the laser showed subtle but distinct apposition of tertiary dentine that was lined with intact odontoblasts. One of the specimens at 3 months revealed the presence of a mild, but very circumscribed, pulpal infiltration of chronic inflammatory cells subjacent to the cavity preparation. The latter is unlikely to be due to a direct effect of the laser irradiation but a possible consequence of microleakage of oral antigens and/or other tissue-irritating molecules through the temporary restoration and the remaining dentine thickness (RDT). Although these preliminary histological results suggest that the CO2 laser under investigation induced only minimal response of the dentine-pulp complex when used as a hard-tissue drilling tool, with specific energy settings, pulse duration within thermal relaxation time and emitting radiations at 9.6 microm of wavelength, larger clinical trials involving various types of teeth are necessary to reach definite conclusions for large-scale clinical application of the laser device.

  11. In vivo evaluation of limonene-based transdermal therapeutic system of nicorandil in healthy human volunteers.

    Science.gov (United States)

    Krishnaiah, Y S R; Chandrasekhar, D V; Rama, B; Jayaram, B; Satyanarayana, V; Al-Saidan, S M

    2005-01-01

    Hydroxypropyl methylcellulose (HPMC) gel drug reservoir system prepared with 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene was effective in promoting the in vitro transdermal delivery of nicorandil. The objective of the present study was to fabricate and evaluate a limonene-based transdermal therapeutic system (TTS) for its ability to provide the desired steady-state plasma concentration of nicorandil in human volunteers. The in vitro permeation of nicorandil from a limonene-based HPMC gel drug reservoir was studied across excised rat skin (control), EVA2825 membrane, adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite to account for their effect on the desired flux of nicorandil. The flux of nicorandil from the limonene-based HMPC drug reservoir across EVA2825 membrane decreased to 215.8 +/- 9.7 microg/cm(2).h when compared to that obtained from control, indicating that EVA2825 was effective as a rate-controlling membrane. The further decrease in nicorandil flux across adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite showed that the adhesive coat and skin also controlled the in vitro transdermal delivery. The limonene-based drug reservoir was sandwiched between adhesive-coated EVA2825-release liner composite and a backing membrane. The resultant sandwich was heat-sealed as circle-shaped patch (20 cm(2)), trimmed and subjected to in vivo evaluation in human volunteers against immediate-release tablets of nicorandil (reference formulation). The fabricated limonene-based TTS of nicorandil provided a steady-state plasma concentration of 21.3 ng/ml up to 24 h in healthy human volunteers. It was concluded that the limonene-based TTS of nicorandil provided the desired plasma concentration of the drug for the predetermined period of time with minimal fluctuations and improved bioavailability.

  12. Analysis of the Chaotic Characteristics of Human Colonic Activities and Comparison of Healthy Participants to Costive Subjects.

    Science.gov (United States)

    Lu, Li; Yan, Guozheng; Zhao, Kai; Xu, Fei

    2016-01-01

    Constipation is a common yet distressing disease that has high rates of morbidity and impacts patients' quality of life. However, there is no perfect method to distinguish costive patients from healthy subjects. Is there chaos in human colonic activities? Are there any differences for the chaos indicators of colonic activities between healthy and costive subjects? Can these indicators distinguish patients with constipation from healthy subjects? To answer these questions, colonic pressure data from 16 healthy subjects and 48 patients with constipation were analyzed using the chaos theory. Three chaotic indicators [i.e., the largest Lyapunov exponent (LyE), correlation dimension (CorDim), and Kolmogorov entropy (KoEn)] were calculated and compared between groups with the Wilcoxon rank sum test. As a result, the LyE was greater than zero and the CorDim was fractioned, which showed that human colonic activities have clear chaotic characteristics. Statistically significant differences were observed between groups for CorDim (p chaotic indicator of CorDim was able to differentiate between patients with constipation and healthy subjects. The chaos theory provides a new method for learning the nonlinear dynamics of human gastrointestinal activities.

  13. Species distribution and physiological characterization of Acinetobacter genospecies from healthy human skin of tribal population in India

    OpenAIRE

    Yavankar S; Pardesi K; Chopade B

    2007-01-01

    Background: Various reports on distribution of Acinetobacter spp. from healthy human skin restricted to urban population. However, no such data is available from healthy human skin of tribal population not exposed to modern antibiotics during their life time. Purpose: Isolation, biotyping, distribution and physiological characterisation of Acinetobacter spp. from healthy human skin of tribal population. Methods: Tribal population of Toranmal area of Satpuda Ranges, Maharashtra, India...

  14. Comparative analysis of twelve Dothideomycete plant pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Ohm, Robin; Aerts, Andrea; Salamov, Asaf; Goodwin, Stephen B.; Grigoriev, Igor

    2011-03-11

    The Dothideomycetes are one of the largest and most diverse groups of fungi. Many are plant pathogens and pose a serious threat to agricultural crops grown for biofuel, food or feed. Most Dothideomycetes have only a single host and related Dothideomycete species can have very diverse host plants. Twelve Dothideomycete genomes have currently been sequenced by the Joint Genome Institute and other sequencing centers. They can be accessed via Mycocosm which has tools for comparative analysis

  15. Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

    Science.gov (United States)

    Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

    2017-02-01

    Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

  16. 4DCT-based assessment of regional airflow distribution in healthy human lungs during tidal breathing

    Science.gov (United States)

    Choi, Jiwoong; Jahani, Nariman; Choi, Sanghun; Hoffman, Eric; Lin, Ching-Long

    2014-11-01

    Nonlinear dynamics of regional airflow distribution in healthy human lungs are studied with four-dimensional computed tomography (4DCT) quantitative imaging of four subjects. During the scanning session, subjects continuously breathed with tidal volumes controlled by the dual piston system. For each subject, 10 instantaneous volumetric image data sets (5 inspiratory and 5 expiratory phases) were reconstructed. A mass-preserving image registration was then applied to pairs of these image data to construct a breathing lung model. Regional distributions of local flow rate fractions are computed from time-varying local air volumes. The 4DCT registration-based method provides the link between local and global air volumes of the lung, allowing derivation of time-varying regional flow rates during the tidal breathing for computational fluid dynamics analysis. The local flow rate fraction remains greater in the lower lobes than in the upper lobes, being qualitatively consistent with those derived from three static CT (3SCT) images (Yin et al. JCP 2013). However, unlike 3SCT, the 4DCT data exhibit lung hysteresis between inspiration and expiration, providing more sensitive measures of regional ventilation and lung mechanics. NIH Grants U01-HL114494, R01-HL094315 and S10-RR022421.

  17. Tactile Toe Agnosia and Percept of a "Missing Toe" in Healthy Humans.

    Science.gov (United States)

    Cicmil, Nela; Meyer, Achim P; Stein, John F

    2016-03-01

    A disturbance of body representation is central to many neurological and psychiatric conditions, but the mechanisms by which body representations are constructed by the brain are not fully understood. We demonstrate a directional disturbance in tactile identification of the toes in healthy humans. Nineteen young adult participants underwent tactile stimulation of the digits with the eyes closed and verbally reported the identity of the stimulated digit. In the majority of individuals, responses to the second and third toes were significantly biased toward the laterally neighboring digit. The directional bias was greater for the nondominant foot and was affected by the identity of the immediately preceding stimulated toe. Unexpectedly, 9/19 participants reported the subjective experience of a "missing toe" or "missing space" during the protocol. These findings challenge current models of somatosensory localization, as they cannot be explained simply by a lack of distinct representations for toes compared with fingers, or by overt toe-finger correspondences. We present a novel theory of equal spatial representations of digit width combined with a "preceding neighbor" effect to explain the observed phenomena. The diagnostic implications for neurological disorders that involve "digit agnosia" are discussed.

  18. Immune response to acetaldehyde-human serum albumin adduct among healthy subjects related to alcohol intake.

    Science.gov (United States)

    Romanazzi, Valeria; Schilirò, Tiziana; Carraro, Elisabetta; Gilli, Giorgio

    2013-09-01

    Acetaldehyde (AA) is the main metabolic product in ethanol metabolism, although it can also derive from sources of airborne pollution. As a typical aldehyde, AA is able to react with a variety of molecular targets, including DNA and protein. This property justifies the hypothesis of a immune reaction against this kind of adduct, to be studied by a seroprevalence screening approach. In this study, the correlation between drinking habits and the amount of circulating AA-human serum albumin adduct (AA-HSA) was evaluated in a group of healthy subjects, non alcohol-addicted. Daily ethanol intake (grams) was inferred for each subject using the information collected through a questionnaire, and AA-HSA antibodies (AA-HSA ab) analyses were performed using the Displacement Assay on whole blood samples. The findings showed a correlation between ethanol intake and immune response to molecular adduct. These results underscore the evaluation of AA-HSA ab amount as a suitable molecular marker for alcohol intake that can be applied in future investigations on a large scale for prevention screening.

  19. Sex differences in healthy human heart rate variability: A meta-analysis.

    Science.gov (United States)

    Koenig, Julian; Thayer, Julian F

    2016-05-01

    The present meta-analysis aimed to quantify current evidence on sex differences in the autonomic control of the heart, indexed by measures of heart rate variability (HRV) in healthy human subjects. An extensive search of the literature yielded 2020 titles and abstracts, of which 172 provided sufficient reporting of sex difference in HRV. Data from 63,612 participants (31,970 females) were available for analysis. Meta-analysis yielded a total of 1154 effect size estimates (k) across 50 different measures of HRV in a cumulated total of 296,247 participants. Females showed a significantly lower mean RR interval and standard deviation of RR intervals (SDNN). The power spectral density of HRV in females is characterized by significantly less total power that contains significantly greater high- (HF) and less low-frequency (LF) power. This is further reflected by a lower LF/HF ratio. Meta-regression revealed significant effects of age, respiration control and the length of recording available for analysis. Although women showed greater mean heart rate, they showed greater vagal activity indexed by HF power of HRV. Underlying mechanisms of these findings are discussed.

  20. No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

    Directory of Open Access Journals (Sweden)

    Aditya Mungee

    2016-11-01

    Full Text Available Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05. Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal did not influence fear memories.

  1. Cholinergic enhancement augments magnitude and specificity of visual perceptual learning in healthy humans.

    Science.gov (United States)

    Rokem, Ariel; Silver, Michael A

    2010-10-12

    Learning through experience underlies the ability to adapt to novel tasks and unfamiliar environments. However, learning must be regulated so that relevant aspects of the environment are selectively encoded. Acetylcholine (ACh) has been suggested to regulate learning by enhancing the responses of sensory cortical neurons to behaviorally relevant stimuli. In this study, we increased synaptic levels of ACh in the brains of healthy human subjects with the cholinesterase inhibitor donepezil (trade name: Aricept) and measured the effects of this cholinergic enhancement on visual perceptual learning. Each subject completed two 5 day courses of training on a motion direction discrimination task, once while ingesting 5 mg of donepezil before every training session and once while placebo was administered. We found that cholinergic enhancement augmented perceptual learning for stimuli having the same direction of motion and visual field location used during training. In addition, perceptual learning with donepezil was more selective to the trained direction of motion and visual field location. These results, combined with previous studies demonstrating an increase in neuronal selectivity following cholinergic enhancement, suggest a possible mechanism by which ACh augments neural plasticity by directing activity to populations of neurons that encode behaviorally relevant stimulus features.

  2. An association between human hippocampal volume and topographical memory in healthy young adults.

    Directory of Open Access Journals (Sweden)

    Tom eHartley

    2012-12-01

    Full Text Available The association between human hippocampal structure and topographical memory was investigated in healthy adults (N=30. Structural MR images were acquired, and voxel-based morphometry (VBM was used to estimate local gray matter volume throughout the brain. A complementary automated mesh-based segmentation approach was used to independently isolate and measure specified structures including the hippocampus. Topographical memory was assessed using a version of the Four Mountains Task, a short test designed to target hippocampal spatial function. Each item requires subjects to briefly study a landscape scene before recognizing the depicted place from a novel viewpoint and under altered non-spatial conditions when presented amongst similar alternative scenes. Positive correlations between topographical memory performance and hippocampal volume were observed in both VBM and segmentation-based analyses. Score on the topographical memory task was also correlated with the volume of some subcortical structures, extra-hippocampal gray matter and total brain volume, with the most robust and extensive covariation seen in circumscribed neocortical regions in the insula and anterior temporal lobes. Taken together with earlier findings, the results suggest that global variations in brain morphology affect the volume of the hippocampus and its specific contribution to topographical memory. We speculate that behavioral variation might arise directly through the impact of resource constraints on spatial representations in the hippocampal formation and its inputs, and perhaps indirectly through an increased reliance on non-allocentric strategies.

  3. Fluorine determination in human healthy and carious teeth using the PIGE technique

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, M.L. E-mail: luisa@alf1.cii.fc.ul.pt; Karydas, A.G.; Casaca, C.; Zarkadas, Ch.; Paradellis, Th.; Kokkoris, M.; Nsouli, B.; Cunha, A.S

    2001-09-01

    The purpose of this study is to determine and compare the fluorine concentration in human teeth from two different populations, living in the Portuguese quite isolated islands of Acores: S. Miguel and Terceira. Both populations have similar dietary habits, similar occupational activities, mostly rural, and the age of both populations is more or less the same, around 40 years. No chronic diseases were registered in any of the donors. The two groups are exposed to different levels of fluorine in drinking water. Terceira island has moderate fluorine concentration levels (1-2 {mu}g g{sup -1}) while S. Miguel island is known for the high fluorine concentration levels in its water (>3 {mu}g g{sup -1}), especially in one area known as Furnas. Thirty-three teeth, 17 healthy and 16 carious without restoration (14 incisors and canines, 7 premolars and 12 molars), were collected and analyzed for the determination of fluorine concentration in the dentine region, using the nuclear reaction {sup 19}F(p,{alpha}{gamma}){sup 16}O. The teeth were cross-sectioned along the vertical plane and polished, in order to obtain a smooth and plane surface of about 1 mm thickness. In this work an association between caries prevalence and fluorine content of drinking water is discussed and the variation of fluorine concentration among different types of teeth (canines and incisors, premolars, molars) and physical state (carious and non-carious) is examined.

  4. Effect of Grewia asiatica fruit on glycemic index and phagocytosis tested in healthy human subjects.

    Science.gov (United States)

    Mesaik, Muhammad Ahmed; Ahmed, Asif; Khalid, Ahmed Shukralla; Jan, Saleem; Siddiqui, Afaq Ahmed; Perveen, Shahida; Azim, Muhammad Kamran

    2013-01-01

    The Grewia asiatica (commonly known as Phalsa or Fasla) is a shrub or small tree found in southern Asia. It produces purple to black color fruit when ripe. In folk medicine the edible Grewia asiatica fruit is used in a number of pathological conditions. The current study described the effects of Grewia asiatica fruit on glycemic index (GI) and phagocytosis in healthy non-diabetic human subjects. The results showed that Grewia asiatica fruit has low GI value of 5.34 with modest hypoglycemic activity. Luminol-enhanced chemiluminescence assay was carried out to determine the production of reactive oxygen species (ROS) in the oxidative burst activity of whole blood. ROS production was found to be significantly affected, having the 78.3, 58.6 and 30.8% when the subjects were fed with D-glucose, mixture of D-glucose and Grewia asiatica fruit and Grewia asiatica fruit alone respectively as compared to the control. The aqueous, methanolic and butanolic extracts of Grewia asiatica fruits were found to produce a stimulatory effect on ROS production however; the chloroform, hexane and ethanol-acetate extracted exerted significant inhibitory effect. These results demonstrated that Grewia asiatica fruit has desirable effects on blood glucose metabolism manifested as low glycemic response and modulation of ROS production.

  5. Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans.

    Science.gov (United States)

    Benson, Sven; Kattoor, Joswin; Wegner, Alexander; Hammes, Florian; Reidick, Daniel; Grigoleit, Jan-Sebastian; Engler, Harald; Oberbeck, Reiner; Schedlowski, Manfred; Elsenbruch, Sigrid

    2012-04-01

    Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.6 ± 1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4 ng/kg) or saline on 2 otherwise identical study days. Blood samples were collected 15 min before and 1, 2, 3, 4, and 6h after injection to characterize changes in immune parameters including proinflammatory cytokines. Rectal sensory and pain thresholds and subjective pain ratings were assessed with barostat rectal distensions 2h after injection. LPS administration induced an acute inflammatory response indicated by transient increases in tumor necrosis factor alpha, interleukin 6, and body temperature (all Pvisceral sensory and pain thresholds (both PVisceral stimuli were rated as more unpleasant (PPain thresholds correlated with interleukin 6 at +1h (r=0.60, Pvisceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. The effects of eating marine- or vegetable-fed farmed trout on the human plasma proteome profiles of healthy men

    DEFF Research Database (Denmark)

    Rentsch, Maria Louise; Lametsch, René; Bügel, Susanne;

    2015-01-01

    of intervention, and after the removal of the twelve most abundant proteins, plasma proteins were separated by two-dimensional gel electrophoresis. Protein spots 4·3 visualised by silver staining were matched by two-dimensional imaging software. Within-subject changes in spots were compared...... between the treatment groups. Differentially affected spots were identified by matrix-assisted laser desorption ionisation-time of flight/time of flight MS and the human Swiss-Prot database. We found 23/681 abundant plasma protein spots, which were up- or down-regulated by the dietary treatment (P...spots differed from those in subjects given the chicken meal, but only three of these were common, and only one spot differed between the two trout groups. In both groups, the affected plasma proteins were involved in biological...

  7. Human milk composition differs in healthy mothers and mothers with celiac disease

    NARCIS (Netherlands)

    Olivares, M.; Albrecht, S.; Palma, de G.; Desamparados Ferrer, M.; Castillejo, G.; Schols, H.A.; Sanz, Y.

    2015-01-01

    Purpose To investigate whether breast-milk composition and microbiota differ in healthy mothers and mothers with celiac disease (CD) to ultimately contribute to identify additional factors determining CD risk. Methods Breast-milk samples from healthy mothers (n = 12) and mothers with CD (n = 12) wer

  8. Twelve tips for peer observation of teaching.

    Science.gov (United States)

    Siddiqui, Zarrin Seema; Jonas-Dwyer, Diana; Carr, Sandra E

    2007-05-01

    This paper outlines twelve tips for undertaking peer observation of teaching in medical education, using the peer review model and the experiences of the authors. An accurate understanding of teaching effectiveness is required by individuals, medical schools, and universities to evaluate the learning environment and to substantiate academic and institutional performance. Peer Observation of Teaching is one tool that provides rich, qualitative evidence for teachers, quite different from closed-ended student evaluations. When Peer Observation of Teaching is incorporated into university practice and culture, and is conducted in a mutually respectful and supportive way, it has the potential to facilitate reflective change and growth for teachers.

  9. Time-of-flight secondary ion mass spectrometry-based molecular distribution distinguishing healthy and osteoarthritic human cartilage

    CERN Document Server

    Cillero-Pastor, Berta; Kiss, Andras; Blanco, Francisco J; Heeren, Ron M A

    2013-01-01

    Osteoarthritis (OA) is a pathology that ultimately causes joint destruction. The cartilage is one of the principal affected tissues. Alterations in the lipid mediators and an imbalance in the metabolism of cells that form the cartilage (chondrocytes) have been described as contributors to the OA development. In this study, we have studied the distribution of lipids and chemical elements in healthy and OA human cartilage. Time of flight-secondary ion mass spectrometry (TOF-SIMS) allows us to study the spatial distribution of molecules at a high resolution on a tissue section. TOF-SIMS revealed a specific peak profile that distinguishes healthy from OA cartilages. The spatial distribution of cholesterol-related peaks exhibited a remarkable difference between healthy and OA cartilages. A distinctive colocalization of cholesterol and other lipids in the superficial area of the cartilage was found. A higher intensity of oleic acid and other fatty acids in the OA cartilages exhibited a similar localization. On the ...

  10. Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy.

    Science.gov (United States)

    González-Barrio, Rocío; Borges, Gina; Mullen, William; Crozier, Alan

    2010-04-14

    The fate of anthocyanins, ellagic acid, and ellagitannins was studied following the consumption of 300 g of raspberries by healthy human volunteers and subjects with an ileostomy. Postingestion plasma and urine from the former and ileal fluid and urine from the latter group were collected and analyzed by HPLC-PDA-MS(2). Plasma from the healthy volunteers did not contain detectable quantities of either the native raspberry polyphenolics or their metabolites. The three main raspberry anthocyanins were excreted in urine in both healthy and ileostomy volunteers 0-7 h after ingestion, in quantities corresponding to urolithin A-O-glucuronide, two of its isomers, and urolithin B-O-glucuronide in urine collected 7-48 h after raspberry consumption. There was marked variation in the urolithin profile of individual volunteers, indicating differences in the colonic microflora responsible for ellagitannin degradation.

  11. Effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants.

    Science.gov (United States)

    Harrison, Neil A; Cercignani, Mara; Voon, Valerie; Critchley, Hugo D

    2015-03-01

    Humans are naturally inquisitive. This tendency is adaptive, aiding identification of potentially valuable novel outcomes. The dopaminergic substantia nigra (SN) is implicated in the drive to explore novel stimuli and situations. However, infection and inflammation inhibit the motivation to seek out novelty. This likely serves to limit exposure to uncertain, potentially detrimental outcomes when metabolic resources are limited. Nevertheless, the neural mechanisms through which inflammation constrains novelty seeking are poorly understood. We therefore scanned 16 healthy participants (6 male, mean 27.2±7.3 years), using fMRI, once following experimental inflammation (intramuscular (i.m.) typhoid vaccination) and once after placebo (i.m. saline), with the aim of characterizing effects of inflammation on neural processing of novel and familiar place, and face stimuli. We specifically tested the effects of inflammation on the hypothesized roles of SN and hippocampus in novelty processing. Typhoid vaccination evoked a nearly threefold increase in circulating pro-inflammatory cytokine (interleukin-6) levels 3 h after injection, indicating induction of mild systemic inflammation. Enhanced hippocampal responses to novel (compared with familiar) stimuli were observed following both vaccine and placebo, consistent with intact central novelty detection. However, the normal bilateral reactivity of SN to stimulus novelty was significantly attenuated following inflammation. Correspondingly, inflammation also markedly impaired novelty-related functional coupling between the SN and hippocampus. These data extend previous findings of SN sensitivity to mild inflammation associated with changes in psychomotor responding, and suggest that inflammation-induced blunting of SN responses to hippocampal novelty signals may represent a plausible mechanism through which inflammation impairs motivational responses to novelty.

  12. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

    Science.gov (United States)

    Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

    2013-01-01

    Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

  13. Brain targeted transcranial administration of diazepam and shortening of sleep latency in healthy human volunteers

    Directory of Open Access Journals (Sweden)

    W Pathirana

    2011-01-01

    Full Text Available Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation

  14. Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors.

    Science.gov (United States)

    Nakamura, Ayumi; Itaki, Chieko; Saito, Ayako; Yonezawa, Toko; Aizawa, Koichi; Hirai, Ayumi; Suganuma, Hiroyuki; Miura, Tomisato; Mariya, Yasushi; Haghdoost, Siamak

    2017-05-12

    Reactive oxygen species (ROS) mediate much of the DNA damage caused by ionizing radiation. Among carotenoids, lycopene and β-carotene, present in tomato juice, are known to be strong radical scavengers. The aim of the study was to investigate the effect of tomato juice intake on the levels of DNA damage and oxidative stress in human whole blood induced by in vitro exposure to X-rays. Ten healthy adults were asked to drink 190 g of tomato juice, containing 17 mg lycopene and 0.25 mg β-carotene, per day for 3 weeks and then refrain from drinking it for 3 weeks. Peripheral whole blood samples were collected before and after the intake period of tomato juice and after the washout period. The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy. Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN) assay and the dicentrics (DIC) assay. The level of oxidative stress was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of carotenoids in plasma was measured at the three time points. The levels of 8-oxo-dG tended to decrease during the intake period and increase during the washout period. A non-significant inverse correlation was noted between the plasma concentration of lycopene plus β-carotene and the level of 8-oxo-dG (P = 0.064). The radiation-induced MN and DIC frequencies increased in a dose-dependent manner, and when compared at the same dose, the MN and DIC frequencies decreased during the intake period compared with those at baseline and then increased during the washout period. The results suggest that continuous tomato juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG and d-ROMs. For most radiation doses, continuously tomato juice intake lowered the levels of MN and DIC. Tomato juice

  15. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    Science.gov (United States)

    Damgaard, Christian; Jensen, Lars J.; Holmstrup, Palle

    2016-01-01

    Background The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. Methods Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode. Results We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. Conclusions Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity. PMID:27672500

  16. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    Directory of Open Access Journals (Sweden)

    Daniel Belstrøm

    2016-09-01

    Full Text Available Background The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. Methods Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode. Results We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. Conclusions Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity.

  17. Reactions of healthy persons and persons suffering from allergic rhinitis when exposed to office dust

    DEFF Research Database (Denmark)

    Hauschildt, Pernille; Mølhave, Lars; Kjærgaard, Søren K.

    1999-01-01

    Objectives Reactions to airborne office dust among healthy subjects and subjects suffering from allergic rhinitis were investigated. Methods Twelve healthy and 11 subjects suffering from allergic rhinitis were exposed to clean air [17 (SD 2) mg/m3] and office dust [439 (SD 68) mg/m3] for 245...... exposure, and some of the indications were in biologically unexplainable directions. No difference in the reactions to dust was observed between the healthy subjects and the subjects suffering from allergic rhinitis. Conclusion Dust does not seem to have objective or subjective effects on humans, as only...

  18. Brain SPECT imaging and whole-body biodistribution with [{sup 123}I]ADAM - a serotonin transporter radiotracer in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Lin, K.-J. [Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Liu, C.-Y. [Neuroscience Research Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Psychiatry, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Wey, S.-P. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Hsiao, I.-T. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Wu, Jay [Health Physics Divisions, Atomic Energy Council, Institute of Nuclear Energy Research, Tao-Yuan 325, Taiwan (China); Fu, Y.-K. [Atomic Energy Council, Institute of Nuclear Energy Research, Tao-Yuan 325, Taiwan (China); Yen, T.-C. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China) and Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China)]. E-mail: yen1110@adm.cgmh.org.tw

    2006-02-15

    Introduction: [{sup 123}I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([{sup 123}I]ADAM), a novel radiotracer, has promising application in the imaging of the serotonin transporter (SERT) in the human brain. In this study, the optimal scanning time for acquiring brain single photon emission computed tomography (SPECT) images was determined by performing dynamic SPECT studies at intervals from 0 to 6 h postinjection of [{sup 123}I]ADAM. Additionally, radiation-absorbed doses were determined for three healthy human subjects using attenuation-corrected images. Methods: Twelve subjects were randomized into one of three study groups as follows: whole-body distribution imaging (n=3), dynamic SPECT imaging (n=3) and brain SPECT imaging (n=6). The radiation-absorbed dose was calculated using MIRDOSE 3.0 software with attenuation-corrected data. The specific binding (SB) ratio of the brain stem was measured from dynamic SPECT images to determine the optimal scanning time. Results: Dynamic SPECT images showed that the SB of the brain stem gradually increased to a maximum 4 h postinjection. Single photon emission computed tomography images at 4 h postinjection showed a high uptake of the radiotracer (SB) in the hypothalamus (1.40{+-}0.12), brain stem (1.44{+-}0.16), pons (1.13{+-}0.14) and medial temporal lobe (0.59{+-}0.10). The mean adult male value of effective dose was 3.37x10{sup -2} mSv/MBq with a 4.8-h urine-voiding interval. Initial high uptake in SERT-rich sites was demonstrated in the lung and brain. A prominent washout of the radiotracer from the lung further increased brain radioactivity that reached a peak value of 5.03% of injected dose 40 min postinjection. Conclusions: [{sup 123}I]ADAM is a promising radiotracer for SPECT imaging of SERT in humans with acceptable dosimetry and high uptake in SERT-rich regions. Brain SPECT images taken within 4 h following injection show optimal levels of radiotracer uptake in known SERT sites. However, dynamic

  19. Combining ability of twelve maize populations

    Directory of Open Access Journals (Sweden)

    Vacaro Elton

    2002-01-01

    Full Text Available Genetic progress depends on germplasm quality and breeding methods. Twelve maize populations and their crosses were evaluated to estimate combining ability and potential to be included as source populations in breeding programs. Plant height, point of insertion of the first ear, number of ears per plant, number of grains per ear, root and stalk lodging and grain yield were studied in two locations in Brazil, during the 1997/98 season. Genotype sum of squares was divided into general (GCA and specific (SCA combining ability. Results indicated the existence of genetic divergence for all traits analyzed, where additive effects were predominant. The high heterosis levels observed, mainly in Xanxerê, suggested the environmental influence on the manifestation of this genetic phenomenon. Populations revealed potential to be used in breeding programs; however, those more intensively submitted to selection could provide larger genetic progress, showing the importance of population improvement for the increment of the heterosis in maize.

  20. Species distribution and physiological characterization of Acinetobacter genospecies from healthy human skin of tribal population in India

    Directory of Open Access Journals (Sweden)

    Yavankar S

    2007-01-01

    Full Text Available Background: Various reports on distribution of Acinetobacter spp. from healthy human skin restricted to urban population. However, no such data is available from healthy human skin of tribal population not exposed to modern antibiotics during their life time. Purpose: Isolation, biotyping, distribution and physiological characterisation of Acinetobacter spp. from healthy human skin of tribal population. Methods: Tribal population of Toranmal area of Satpuda Ranges, Maharashtra, India were sampled for ten body sites. Tentative Acinetobacter isolates were confirmed to the genus level by chromosomal DNA transformation assay and to species level using Bouvet and Grimont system. Novel physiological characteristics like pH, temperature and salt tolerance were studied. All strains were screened for production of various enzymes. Results: One hundred and eighteen strains were isolated, which belonged to nine Acinetobacter genospecies. A. haemolyticus was most abundant followed by A. calcoaceticus and A. genospecies 1-3. Higher percentage of Acinetobacter was recovered from skin of nose, Pawara tribe and female volunteers. They showed wide variation in temperature, salt and pH tolerance. Most of the strains could produce enzymes viz, lipase, esterase, urease and amylase. Conclusions: Acinetobacter spp. belonging to nine genospecies were obtained in the present study. Physiological characteristics including high salt, temperature and acidic pH tolerance were helpful to differentiate between the commensal and pathogenic species of Acinetobacter genus.

  1. Cardiac lipid levels show diurnal changes and long-term variations in healthy human subjects.

    Science.gov (United States)

    Ith, Michael; Stettler, Christoph; Xu, Jian; Boesch, Chris; Kreis, Roland

    2014-11-01

    (1) H-MRS is regularly applied to determine lipid content in ectopic tissue - mostly skeletal muscle and liver - to investigate physiological and/or pathologic conditions, e.g. insulin resistance. Technical developments also allow non-invasive in vivo assessment of cardiac lipids; however, basic data about methodological reliability (repeatability) and physiological variations are scarce. The aim of the presented work was to determine potential diurnal changes of cardiac lipid stores in humans, and to put the results in relation to methodological repeatability and normal physiological day-to-day variations. Optimized cardiac- and respiratory-gated (1) H-MRS was used for non-invasive quantification of intracardiomyocellular lipids (ICCL), creatine, trimethyl-ammonium compounds (TMA), and taurine in nine healthy young men at three time points per day on two days separated by one week. This design allowed determination of (a) diurnal changes, (b) physiological variation over one week and (c) methodological repeatability of the ICCL levels. Comparison of fasted morning to post-absorptive evening measurements revealed a significant 37 ± 19% decrease of ICCL during the day (p = 0.0001). There was a significant linear correlation between ICCL levels in the morning and their decrease during the day (p = 0.015). Methodological repeatability for the ICCL/creatine ratio was excellent, with a coefficient of variance of ~5%, whereas physiological variation was found to be considerably higher (22%) in spite of a standardized physiological preparation protocol. In contrast, TMA levels remained stable over this time period. The proposed (1) H-MRS technique provides a robust way to investigate relevant physiological changes in cardiac metabolites, in particular ICCL. The present results suggest that ICCL reveal a diurnal course, with higher levels in the morning as compared to evening. In addition, a considerable long-term variation of ICCL levels, in both the morning and evening

  2. Vitamin D Levels Are Associated with Cardiac Autonomic Activity in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Linda Ellis

    2013-06-01

    Full Text Available Vitamin D deficiency (≤50nmol/L 25-hydroxy vitamin D is a cardiovascular (CV risk factor that affects approximately one billion people worldwide, particularly those affected by chronic kidney disease (CKD. Individuals with CKD demonstrate abnormal cardiac autonomic nervous system activity, which has been linked to the significant rates of CV-related mortality in this population. Whether vitamin D deficiency has a direct association with regulation of cardiac autonomic activity has never been explored in humans. Methods: Thirty-four (34 healthy, normotensive subjects were studied and categorized based on 25-hydroxy vitamin D deficiency (deficient vs. non-deficient, n = 7 vs. 27, as well as 1,25-dihydroxy vitamin D levels (above vs. below 25th percentile, n = 8 vs. 26. Power spectral analysis of electrocardiogram recordings provided measures of cardiac autonomic activity across low frequency (LF and high frequency (HF, representative of vagal contribution bands, representative of the sympathetic and vagal limbs of the autonomic nervous system when transformed to normalized units (nu, respectively, as well as overall cardiosympathovagal balance (LF:HF during graded angiotensin II (AngII challenge (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min. Results: At baseline, significant suppression of sympathovagal balance was observed in the 25-hydroxy vitamin D-deficient participants (LF:HF, p = 0.02 vs. non-deficient, although no other differences were observed throughout AngII challenge. Participants in the lowest 1,25-dihydroxy VD quartile experienced significant withdrawal of inhibitory vagal control, as well as altered overall sympathovagal balance throughout AngII challenge (HF, mean difference = −6.98 ± 3 nu, p = 0.05; LF:HF, mean difference = 0.34 ± 0.1, p = 0.043 vs. above 25th percentile. Conclusions: Vitamin D deficiency is associated with suppression of resting cardiac autonomic activity, while low 1,25-dihydroxy vitamin D levels are

  3. Acute moderate elevation of TNF-{alpha} does not affect systemic and skeletal muscle protein turnover in healthy humans

    DEFF Research Database (Denmark)

    Petersen, Anne Marie; Plomgaard, Peter; Fischer, Christian P;

    2009-01-01

    -alpha infusion (rhTNF-alpha). We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibit synthesis. Subjects and Methods: Using a randomized controlled, crossover design post-absorptive healthy young males (n=8) were studied 2 hours under basal conditions followed by 4 hours infusion......Context: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha. Objective: In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover, via a 4 hours recombinant human TNF...... of either rhTNF-alpha (700 ng.m(-2).h(-1)) or 20% human albumin (Control) which was the vehicle of rhTNF-alpha. Systemic and skeletal muscle protein turnover were estimated by a combination of tracer dilution methodology (primed continuous infusion of L-[ring-(2)H5]phenylalanine and L-[(15)N...

  4. The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.

    Science.gov (United States)

    Trabado, Séverine; Al-Salameh, Abdallah; Croixmarie, Vincent; Masson, Perrine; Corruble, Emmanuelle; Fève, Bruno; Colle, Romain; Ripoll, Laurent; Walther, Bernard; Boursier-Neyret, Claire; Werner, Erwan; Becquemont, Laurent; Chanson, Philippe

    2017-01-01

    Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.

  5. Impact of human coronavirus infections in otherwise healthy children who attended an emergency department

    NARCIS (Netherlands)

    Esposito, Susanna; Bosis, Samantha; Niesters, Hubert G M; Tremolati, Elena; Begliatti, Enrica; Rognoni, Alessandro; Tagliabue, Claudia; Principi, Nicola; Osterhaus, Albert D M E

    2006-01-01

    This prospective clinical and virological study of 2,060 otherwise healthy children aged <15 years of age (1,112 males; mean age +/- SD, 3.46 +/- 3.30 years) who attended the Emergency Department of Milan University's Institute of Pediatrics because of an acute disease excluding trauma during the wi

  6. Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik; Thomsen, Carsten E; Høgenhaven, Hans;

    2008-01-01

    cognitive function during hypoglycaemia. METHODS: Sixteen healthy volunteers selected by either particularly high or low serum ACE activity were subjected to hypoglycaemia (plasma glucose 2.7 mmol/L). Cognitive function was assessed by choice reaction tests. RESULTS: Despite a similar hypoglycaemic stimulus...

  7. Proton and phosphorus magnetic resonance spectroscopy of the healthy human breast at 7 T

    NARCIS (Netherlands)

    van der Kemp, Wybe J M; Stehouwer, Bertine L; Boer, Vincent O; Luijten, Peter R; Klomp, DWJ; Wijnen, Jannie P

    In vivo water- and fat-suppressed (1) H magnetic resonance spectroscopy (MRS) and (31) P magnetic resonance adiabatic multi-echo spectroscopic imaging were performed at 7 T in duplicate in healthy fibroglandular breast tissue of a group of eight volunteers. The transverse relaxation times of (31) P

  8. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Søndergaard, S B; Fuglsang, Stefan;

    2004-01-01

    . METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure...

  9. Pulse-wave morphology and pulse-wave velocity in healthy human volunteers

    DEFF Research Database (Denmark)

    Frimodt-Møller, M; Nielsen, A H; Kamper, A-L

    2006-01-01

    and of the brachial and aortic PWV on the right and left side of the body were recorded in 23 healthy subjects by two trained observers. Measurements were performed in the fasting state and 3 h after a high-calorie meal, and before and 1 h after smoking a cigarette. RESULTS: Intake of a high-calorie meal as well...

  10. Discrete Scale Invariance in the Cascade Heart Rate Variability Of Healthy Humans

    CERN Document Server

    Lin, D C

    2004-01-01

    Evidence of discrete scale invariance (DSI) in daytime healthy heart rate variability (HRV) is presented based on the log-periodic power law scaling of the heart beat interval increment. Our analysis suggests multiple DSI groups and a dynamic cascading process. A cascade model is presented to simulate such a property.

  11. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    Science.gov (United States)

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

  12. Respiratory Effects of the Nociceptin/Orphanin FQ Peptide and Opioid Receptor Agonist, Cebranopadol, in Healthy Human Volunteers.

    Science.gov (United States)

    Dahan, Albert; Boom, Merel; Sarton, Elise; Hay, Justin; Groeneveld, Geert Jan; Neukirchen, Meike; Bothmer, John; Aarts, Leon; Olofsen, Erik

    2017-04-01

    Cebranopadol is a novel strong analgesic that coactivates the nociceptin/orphanin FQ receptor and classical opioid receptors. There are indications that activation of the nociceptin/orphanin FQ receptor is related to ceiling in respiratory depression. In this phase 1 clinical trial, we performed a pharmacokinetic-pharmacodynamic study to quantify cebranopadol's respiratory effects. Twelve healthy male volunteers received 600 μg oral cebranopadol as a single dose. The following main endpoints were obtained at regular time intervals for 10 to 11 h after drug intake: ventilation at an elevated clamped end-tidal pressure of carbon dioxide, pain threshold and tolerance to a transcutaneous electrical stimulus train, and plasma cebranopadol concentrations. The data were analyzed using sigmoid Emax (respiration) and power (antinociception) models. Cebranopadol displayed typical opioid-like effects including miosis, analgesia, and respiratory depression. The blood-effect-site equilibration half-life for respiratory depression and analgesia was 1.2 ± 0.4 h (median ± standard error of the estimate) and 8.1 ± 2.5 h, respectively. The effect-site concentration causing 50% respiratory depression was 62 ± 4 pg/ml; the effect-site concentration causing 25% increase in currents to obtain pain threshold and tolerance was 97 ± 29 pg/ml. The model estimate for minimum ventilation was greater than zero at 4.9 ± 0.7 l/min (95% CI, 3.5 to 6.6 l/min). At the dose tested, cebranopadol produced respiratory depression with an estimate for minimum ventilation greater than 0 l/min. This is a major advantage over full μ-opioid receptor agonists that will produce apnea at high concentrations. Further clinical studies are needed to assess whether such behavior persists at higher doses.

  13. ERIC-PCR fingerprinting-based community DNA hybridization to pinpoint genome-specific fragments as molecular markers to identify and track populations common to healthy human guts.

    Science.gov (United States)

    Wei, Guifang; Pan, Li; Du, Huimin; Chen, Junyi; Zhao, Liping

    2004-10-01

    Bacterial populations common to healthy human guts may play important roles in human health. A new strategy for discovering genomic sequences as markers for these bacteria was developed using Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR fingerprinting. Structural features within microbial communities are compared with ERIC-PCR followed by DNA hybridization to identify genomic fragments shared by samples from healthy human individuals. ERIC-PCR profiles of fecal samples from 12 diseased or healthy human and piglet subjects demonstrated stable, unique banding patterns for each individual tested. Sequence homology of DNA fragments in bands of identical size was examined between samples by hybridization under high stringency conditions with DIG-labeled ERIC-PCR products derived from the fecal sample of one healthy child. Comparative analysis of the hybridization profiles with the original agarose fingerprints identified three predominant bands as signatures for populations associated with healthy human guts with sizes of 500, 800 and 1000 bp. Clone library profiling of the three bands produced 17 genome fragments, three of which showed high similarity only with regions of the Bacteroides thetaiotaomicron genome, while the remainder were orphan sequences. Association of these sequences with healthy guts was validated by sequence-selective PCR experiments, which showed that a single fragment was present in all 32 healthy humans and 13 healthy piglets tested. Two fragments were present in the healthy human group and in 18 children with non-infectious diarrhea but not in eight children with infectious diarrhea. Genome fragments identified with this novel strategy may be used as genome-specific markers for dynamic monitoring and sequence-guided isolation of functionally important bacterial populations in complex communities such as human gut microflora.

  14. Twelve tips for getting your manuscript published.

    Science.gov (United States)

    Cook, David A

    2016-01-01

    The author shares twelve practical tips on how to navigate the process of getting a manuscript published. These tips, which apply to all fields of academic writing, advise that during the initial preparation phase authors should: (1) plan early to get it out the door; (2) address authorship and writing group expectations up front; (3) maintain control of the writing; (4) ensure complete reporting; (5) use electronic reference management software; (6) polish carefully before they submit; (7) select the right journal; and (8) follow journal instructions precisely. Rejection after the first submission is likely, and when this occurs authors should (9) get it back out the door quickly, but first (10) take seriously all reviewer and editor suggestions. Finally, when the invitation comes to revise and resubmit, authors should (11) respond carefully to every reviewer suggestion, even if they disagree, and (12) get input from others as they revise. The author also shares detailed suggestions on the creation of effective tables and figures, and on how to respond to reviewer critiques.

  15. Antifouling activity of twelve demosponges from Brazil

    Directory of Open Access Journals (Sweden)

    SM. Ribeiro

    Full Text Available Benthic marine organisms are constantly exposed to fouling, which is harmful to most host species. Thus, the production of secondary metabolites containing antifouling properties is an important ecological advantage for sessile organisms and may also provide leading compounds for the development of antifouling paints. High antifouling potential of sponges has been demonstrated in the Indian and Pacific oceans and in the Caribbean and Mediterranean seas. Brazilian sponges remain understudied concerning antifouling activities. Only two scientific articles reported this activity in sponges of Brazil. The objective of this study was to test crude extracts of twelve species of sponges from Brazil against the attachment of the mussel Perna perna through laboratorial assays, and highlight promising species for future studies. The species Petromica citrina, Amphimedon viridis, Desmapsamma anchorata, Chondrosia sp., Polymastia janeirensis, Tedania ignis, Aplysina fulva, Mycale angulosa, Hymeniacidon heliophila, Dysidea etheria, Tethya rubra, and Tethya maza were frozen and freeze-dried before extraction with acetone or dichloromethane. The crude extract of four species significantly inhibited the attachment of byssus: Tethya rubra (p = 0.0009, Tethya maza (p = 0.0039, Petromica citrina (p = 0.0277, and Hymeniacidon heliophila (p = 0.00003. These species, specially, should be the target of future studies to detail the substances involved in the ability antifouling well as to define its amplitude of action.

  16. Twelve Elastic Constants of Betula platyphylla Suk.

    Institute of Scientific and Technical Information of China (English)

    Wang Liyu; Lu Zhenyou

    2004-01-01

    Wood elastic constants are needed to describe the elastic behaviors of wood and be taken as an important design parameter for wood-based composite materials and structural materials. This paper clarified the relationships between compliance coefficients and engineering elastic constants combined with orthotropic properties of wood, and twelve elastic constants of Betula platyphylla Suk. were measured by electrical strain gauges. Spreading the adhesive quantity cannot be excessive or too little when the strain flakes were glued. If excessive, the glue layer was too thick which would influence the strain flakes' performance, and if too little, glues plastered were not firm, which could not accurately transmit the strain. Wood as an orthotropic material, its modulus of elasticity and poisson's ratios are related by two formulas:μij /Ei =μji /Ej and μij 0.95) between the reciprocal of elastic modulus MOE-1 and the square of the ratio of depth to length (h/l)2, which indicate that shear modulus values measured were reliable by three point bending experiment.

  17. Meal-induced changes in splanchnic blood flow and oxygen uptake in middle-aged healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Søndergaard, SB; Møller, Søren

    2006-01-01

    OBJECTIVE: For decades, the determination of changes in splanchnic blood flow and oxygen uptake after a meal has been used in the management of patients with suspected chronic intestinal ischaemia. However, little is known about the normal meal-induced responses. The aim of the present study...... was therefore to measure the splanchnic blood flow and oxygen uptake before and after a standardized meal in a group of middle-aged normal volunteers. MATERIAL AND METHODS: Splanchnic blood flow and oxygen uptake were determined at baseline and after a 3600-kJ mixed meal in 8 healthy women (50-70 years) and 10...... in middle-aged healthy humans. Our data may be relevant for the evaluation of corresponding data from patients with suspected chronic intestinal ischaemia....

  18. Brazilian propolis promotes immunomodulation on human cells from American Tegumentar Leishmaniasis patients and healthy donors infected with L. braziliensis.

    Science.gov (United States)

    Dos Santos Thomazelli, Ana Paula Fortes; Tomiotto-Pellissier, Fernanda; da Silva, Suelen Santos; Panis, Carolina; Orsini, Tatiane Marcusso; Cataneo, Allan Henrique Depieri; Miranda-Sapla, Milena Menegazzo; Custódio, Luiz Antonio; Tatakihara, Vera Lúcia Hideko; Bordignon, Juliano; Silveira, Guilherme Ferreira; Sforcin, José Maurício; Pavanelli, Wander Rogério; Conchon-Costa, Ivete

    2017-01-01

    American Tegumentar Leishmaniasis (ATL) is an infectious disease caused by Leishmania parasites with ineffective treatment. The properties of propolis have been studied in different experimental studies, however, few works have investigated the effects of propolis on human-derived peripheral blood mononuclear cells (PBMC) in leishmaniasis models. Thus, we investigate the immunomodulatory effects of propolis treatment on PBMC from ATL patients and on PBMC from healthy donors infected with Leishmania braziliensis. Our data demonstrate that propolis pretreatment shows immunomodulatory effects on both healthy donors and ATL patients adherent cells, increasing IL-4 and IL-17 and decreasing IL-10, in either the presence or absence of the L. braziliensis infection, demonstrating that propolis contributes with the decrease of the inflammation and could also contribute with parasite control. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effects of melatonin on prepulse inhibition, habituation and sensitization of the human startle reflex in healthy volunteers

    DEFF Research Database (Denmark)

    Lehtinen, Emilia K; Ucar, Ebru; Glenthøj, Birte Y

    2014-01-01

    Prepulse inhibition of the startle reflex (PPI) is an operational measure of sensorimotor gating, which is demonstrated to be impaired in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with blunted melatonin secretion is regularly found in patients...... with schizophrenia and it is theorized that these may contribute to their attentional deficits. The aim of this study was to assess the effects of acute melatonin on healthy human sensorimotor gating. Twenty-one healthy male volunteers were administered melatonin or placebo after which their levels of PPI were...... assessed. Melatonin significantly reduced startle magnitude and ratings of alertness, but did not influence PPI, nor sensitization and habituation. However, when taking baseline scores in consideration, melatonin significantly increased PPI in low scoring individuals while significantly decreasing...

  20. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    : To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...... of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean...... emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl...

  1. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars

    2016-01-01

    Objective: The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6) developed for controlled ovarian stimulation prior to assisted...... reproductive technologies. Methods: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed...... effects population pharmacokinetic modelling in NONMEM 7.2.0. Results: A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent...

  2. Potassium currents in human myogenic cells from healthy and congenital myotonic dystrophy foetuses.

    Science.gov (United States)

    Nurowska, Ewa; Constanti, Andrew; Dworakowska, Beata; Mouly, Vincent; Furling, Denis; Lorenzon, Paola; Pietrangelo, Tiziana; Dołowy, Krzysztof; Ruzzier, Fabio

    2009-01-01

    The whole-cell patch clamp technique was used to record potassium currents in in vitro differentiating myoblasts isolated from healthy and myotonic dystrophy type 1 (DM1) foetuses carrying 2000 CTG repeats. The fusion of the DM1 myoblasts was reduced in comparison to that of the control cells. The dystrophic muscle cells expressed less voltage-activated K(+) (delayed rectifier and non-inactivating delayed rectifier) and inward rectifier channels than the age-matched control cells. However, the resting membrane potential was not significantly different between the control and the DM1 cells. After four days in a differentiation medium, the dystrophic cells expressed the fast-inactivating transient outward K(+) channels, which were not observed in healthy cells. We suggest that the low level of potassium currents measured in differentiated DM1 cells could be related to their impaired fusion.

  3. Long-Time Autocorrelation Function of ECG Signal for Healthy versus Diseased Human Heart

    Science.gov (United States)

    Kulessa, B.; Srokowski, T.; Drozdz, S.

    2003-01-01

    Long-time ECG time series for healthy subjects and diseased patients are analysed. In the first case, the power spectrum has the 1/f shape in a broad frequency range. However, its behaviour for very low and very high frequency is different and the entire spectrum is integrable. For patients with post-ictal heart rate oscillation in partial epilepsy the 1/f noise is not present. We determine the power spectrum by evaluating the Fourier transform of the signal in both cases and calculate the signal autocorrelation function. It falls with time faster for diseased patients then for healthy people. The presented method can serve as a diagnostic tool of some heart diseases.

  4. The neurophysiology of language: Insights from non-invasive brain stimulation in the healthy human brain.

    Science.gov (United States)

    Hartwigsen, Gesa

    2015-09-01

    With the advent of non-invasive brain stimulation (NIBS), a new decade in the study of language has started. NIBS allows for testing the functional relevance of language-related brain activation and enables the researcher to investigate how neural activation changes in response to focal perturbations. This review focuses on the application of NIBS in the healthy brain. First, some basic mechanisms will be introduced and the prerequisites for carrying out NIBS studies of language are addressed. The next section outlines how NIBS can be used to characterize the contribution of the stimulated area to a task. In this context, novel approaches such as multifocal transcranial magnetic stimulation and the condition-and-perturb approach are discussed. The third part addresses the combination of NIBS and neuroimaging in the study of plasticity. These approaches are particularly suited to investigate short-term reorganization in the healthy brain and may inform models of language recovery in post-stroke aphasia.

  5. 3-D ultrastructure and collagen composition of healthy and overloaded human tendon

    DEFF Research Database (Denmark)

    Pingel, Jessica; Lu, Yinhui; Starborg, Tobias

    2014-01-01

    block face-scanning electron microscopy were made on two individuals. In the tendinopathic regions, compared with the flanking healthy tissue, we observed: (i) an increase in the ratio of collagen III : I proteins; (ii) buckling of the collagen fascicles in the ECM; (iii) buckling of tenocytes......Achilles tendinopathies display focal tissue thickening with pain and ultrasonography changes. Whilst complete rupture might be expected to induce changes in tissue organization and protein composition, little is known about the consequences of non-rupture-associated tendinopathies, especially...... with regards to changes in the content of collagen type I and III (the major collagens in tendon), and changes in tendon fibroblast (tenocyte) shape and organization of the extracellular matrix (ECM). To gain new insights, we took biopsies from the tendinopathic region and flanking healthy region of Achilles...

  6. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia

    DEFF Research Database (Denmark)

    Meier, J J; Gallwitz, B; Siepmann, N

    2003-01-01

    secretion under normoglycaemic conditions. METHODS: Ten healthy subjects (9 men, 1 woman; age 33+/-11; BMI 26.8+/-2.2 kg/m(2)) received three different doses of intravenous GIP (7, 20, and 60 pmol/kg body weight) and placebo. Venous blood samples were drawn over 30 min for glucagon and GIP concentrations...... (specific radioimmunoassays). In addition, 31 healthy subjects (16 men, 15 women; 42+/-11 years; BMI 24.4+/-2.7 kg/m(2)) were studied with 20 pmol GIP/kg. Statistics were done with RM-ANOVA and Duncan's post hoc tests. RESULTS: Gastric inhibitory polypeptide dose-dependently stimulated glucagon secretion...... ( p=0.019) with a maximal increment after 10 min. Incremental glucagon concentrations (Delta(10-0 min)) were 0.1+/-0.7, 1.4+/-0.5, 2.4+/-0.5, and 3.4+/-0.8 pmol/l (for placebo and for 7, 20, and 60 pmol GIP/kg, respectively; p=0.017). After the injection of 20 pmol GIP/kg b.w. in 31 healthy subjects...

  7. Does forward head posture affect postural control in human healthy volunteers?

    Science.gov (United States)

    Silva, Anabela G; Johnson, Mark I

    2013-06-01

    Proprioceptive afferent input from neck muscles plays an important role in postural control. Forward head posture has the potential to impair proprioceptive information from neck muscles and contribute to postural control deficits in patients with neck pain. This study investigated whether induced forward head posture affects postural control in healthy participants when compared to natural head posture. Centre of pressure sway area, distance covered and mean velocity were measured during 30s of static standing using a force platform with 25 healthy individuals (mean age ± SD = 20.76 ± 2.19 years) in 8 different conditions. Base of support, eyes open or closed and natural or forward head posture varied within these testing conditions. The majority of comparisons between natural and forward head posture were not statistically significant (p>0.05). This suggests that induced forward head posture in young healthy adults does not challenge them enough to impair postural control. Future studies should evaluate whether forward head posture affects postural control of individuals with chronic neck pain.

  8. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

    National Research Council Canada - National Science Library

    Jonge, de, E; Friederich, P.W; Vlasuk, G.P; Rote, W; Vroom, M.B; Levi, M.M; Poll, van der, T

    2003-01-01

    .... Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma...

  9. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences.

    Science.gov (United States)

    Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

    2015-03-03

    NAD is an essential metabolite that exists in NAD(+) or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD(+)/NADH redox state and modulating cellular signaling processes through the activity of the NAD(+)-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD(+) and NADH contents and the NAD(+)/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD(+), total NAD contents, and NAD(+)/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.

  10. What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

    Science.gov (United States)

    Ruiz, Lorena; Espinosa-Martos, Irene; García-Carral, Cristina; Manzano, Susana; McGuire, Michelle K.; Meehan, Courtney L.; McGuire, Mark A.; Williams, Janet E.; Foster, James; Sellen, Daniel W.; Kamau-Mbuthia, Elizabeth W.; Kamundia, Egidioh W.; Mbugua, Samwel; Moore, Sophie E.; Kvist, Linda J.; Otoo, Gloria E.; Lackey, Kimberly A.; Flores, Katherine; Pareja, Rossina G.; Bode, Lars; Rodríguez, Juan M.

    2017-01-01

    Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the “core” soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02670278. PMID:28713365

  11. Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: A TMS study

    Directory of Open Access Journals (Sweden)

    Ilić Nela V.

    2012-01-01

    Full Text Available Introduction. Administration of pharmacological agents with specific actions on neurotransmitter systems is a powerful driver of functional cortical reorganization. Plastic reorganization of the motor cortex in humans studies by the use of non-invasive stimulation protocols, which mimic the Hebbian model of associative plasticity. Objective. Aiming to explore pharmacological modulation on human motor cortex plasticity, we tested healthy subjects after each dosage of diazepam, levodopa i placebo administration, using paired associative stimulation protocol (PAS that induce fenomena similar to a long-term potentiation and depression, as defined on the synaptic level. Methods. We analyzed effects of benzodiazepines (10 mg, levodopa (200 mg and placebo on PAS protocol in 14 healthy volunteers, using a double-blind placebo-controlled study design. PAS consisted of electrical stimuli pairs at n.medianus and magnetic pulses over the scalp (transcranial magnetic stimulation in precisely defined intervals (ISI was 10 and 25 ms for a total of about 15 minutes (200 pairs. MEP amplitudes before and after (0, 10, 20 and 30 minutes later interventional protocols were compared. Results. When protocols were applied with placebo depending on ISI (10 ms - inhibitory, 25 ms - facilitatory effects, MEP amplitudes decreased or increased, while values in the postinterventional period (0, 10, 20 and 30 min were compared with initial values before the use of SAS. The use of benzodiazepines caused the occlusion of LTP-like effect, in contrast to amplification effects recorded after the administration of levodopa. With respect to the LTD-like protocol, the reverse was true (ANOVA for repeat measurements p<0.001. Conclusion. Administration of GABA-ergic agonist diazepam interferes with the induction of associative plasticity in the motor cortex of healthy individuals, as opposed to the use of levodopa, which stimulates these processes. The observed effects point at a

  12. Inducing Acute Traumatic Coagulopathy In Vitro: The Effects of Activated Protein C on Healthy Human Whole Blood.

    Directory of Open Access Journals (Sweden)

    Benjamin M Howard

    Full Text Available Acute traumatic coagulopathy has been associated with shock and tissue injury, and may be mediated via activation of the protein C pathway. Patients with acute traumatic coagulopathy have prolonged PT and PTT, and decreased activity of factors V and VIII; they are also hypocoagulable by thromboelastometry (ROTEM and other viscoelastic assays. To test the etiology of this phenomenon, we hypothesized that such coagulopathy could be induced in vitro in healthy human blood with the addition of activated protein C (aPC.Whole blood was collected from 20 healthy human subjects, and was "spiked" with increasing concentrations of purified human aPC (control, 75, 300, 2000 ng/mL. PT/PTT, factor activity assays, and ROTEM were performed on each sample. Mixed effect regression modeling was performed to assess the association of aPC concentration with PT/PTT, factor activity, and ROTEM parameters.In all subjects, increasing concentrations of aPC produced ROTEM tracings consistent with traumatic coagulopathy. ROTEM EXTEM parameters differed significantly by aPC concentration, with stepwise prolongation of clotting time (CT and clot formation time (CFT, decreased alpha angle (α, impaired early clot formation (a10 and a20, and reduced maximum clot firmness (MCF. PT and PTT were significantly prolonged at higher aPC concentrations, with corresponding significant decreases in factor V and VIII activity.A phenotype of acute traumatic coagulopathy can be induced in healthy blood by the in vitro addition of aPC alone, as evidenced by viscoelastic measures and confirmed by conventional coagulation assays and factor activity. This may lend further mechanistic insight to the etiology of coagulation abnormalities in trauma, supporting the central role of the protein C pathway. Our findings also represent a model for future investigations in the diagnosis and treatment of acute traumatic coagulopathy.

  13. What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

    Directory of Open Access Journals (Sweden)

    Lorena Ruiz

    2017-06-01

    Full Text Available Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα, acquired immunity factors (IL2, IL4, IL10, IL13, IL17, chemokines (IL8, Groα, MCP1, MIP1β, growth factors [IL5, IL7, epidermal growth factor (EGF, granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM, in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the “core” soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02670278.

  14. Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial

    OpenAIRE

    Nair, P N R; Duncan, H F; Pitt Ford, T. R.; Luder, H U

    2008-01-01

    AIM: To investigate the pulpal response to direct pulp capping in healthy human teeth with mineral trioxide aggregate (MTA) as against calcium hydroxide cement (Dycal) as control. METHODOLOGY: Twenty healthy human third molars had iatrogenic pulpotomy and direct pulp capping with MTA. Another 13 teeth were capped with Dycal as controls. The teeth were restored, with IRM, clinically reviewed and extracted after a number of pre-determined intervals (1 week, 1 month and 3 months). The specimens ...

  15. The number and distribution of blood dendritic cells in the epidermis and dermis of healthy human subjects.

    Science.gov (United States)

    Narbutt, Joanna; Lesiak, Aleksandra; Sysa-Jedrzejowska, Anna; Smolewski, Piotr; Robak, Tadeusz; Zalewska, Anna

    2006-01-01

    Human blood dendritic cells (BDC) can be divided into three subsets: plasmacytoid DC (PDC) and two myeloid subsets--MDC1 and MDC2. Several studies revealed the presence of both MDC and PDC in blood of healthy subjects, however no precise literature data exist on the number and distribution of BDC in the skin. The aim of our study was to assess the number and distribution of BDC and their subtypes in the healthy skin. The-study included 30 healthy volunteers (age 18-51). Punch biopsies were taken from the buttock skin from each subject, and immunofluorescent staining was performed using monoclonal mouse IgG1 antibodies directed against BDCA-1, BDCA-2, BDCA-3 and BDC-4. The BDC were present both in the epidermis and dermis. PDC were detected mainly in the dermis (mean 1.2 cells per field). Myeloid subtypes were observed mainly in the middle layers of the epidermis and in the upper part of the dermis (mean 1.8 cells per field). The detection of blood dendritic cells in the skin proves their role in immune cutaneous surveillance.

  16. A comparative proteomic study of human skin suction blister fluid from healthy individuals using immunodepletion and iTRAQ labeling.

    Science.gov (United States)

    Müller, André C; Breitwieser, Florian P; Fischer, Heinz; Schuster, Christopher; Brandt, Oliver; Colinge, Jacques; Superti-Furga, Giulio; Stingl, Georg; Elbe-Bürger, Adelheid; Bennett, Keiryn L

    2012-07-06

    Aberrations in skin morphology and functionality can cause acute and chronic skin-related diseases that are the focus of dermatological research. Mechanically induced skin suction blister fluid may serve as a potential, alternative human body fluid for quantitative mass spectrometry (MS)-based proteomics in order to assist in the understanding of the mechanisms and causes underlying skin-related diseases. The combination of abundant-protein removal with iTRAQ technology and multidimensional fractionation techniques improved the number of identified protein groups. A relative comparison of a cohort of 8 healthy volunteers was thus recruited in order to assess the net variability encountered in a healthy scenario. The technology enabled the identification, to date, of the highest number of reported protein groups (739) with concomitant relative quantitative data for over 90% of all proteins with high reproducibility and accuracy. The use of iTRAQ 8-plex resulted in a 66% decrease in protein identifications but, despite this, provided valuable insight into interindividual differences of the healthy control samples. The geometric mean ratio was close to 1 with 95% of all ratios ranging between 0.45 and 2.05 and a calculated mean coefficient of variation of 15.8%, indicating a lower biological variance than that reported for plasma or urine. By applying a multistep sample processing, the obtained sensitivity and accuracy of quantitative MS analysis demonstrates the prospective value of the approach in future research into skin diseases.

  17. Detection of human papillomavirus in nonmelanoma skin cancer lesions and healthy perilesional skin in kidney transplant recipients and immunocompetent patients.

    Science.gov (United States)

    Bernat-García, J; Morales Suárez-Varela, M; Vilata-Corell, J J; Marquina-Vila, A

    2014-04-01

    The influence of human papillomavirus (HPV) on the development of nonmelanoma skin cancer (NMSC) is a topic of debate. HPV types from the beta genus (HPV-β) have been most frequently associated with the development of skin cancer. To analyze the prevalence and range of HPV types in NMSC lesions and healthy perilesional skin in immunodepressed and immunocompetent patients and to evaluate the influence of various clinical factors on the prevalence of HPV in skin cancer. Nested polymerase chain reaction and sequencing were used to detect HPV in 120 NMSC samples obtained by biopsy from 30 kidney transplant recipients and 30 immunocompetent patients. In all cases, a sample was taken from the tumor site and the surrounding healthy skin. Potential confounders were assessed and the data analyzed by multivariate logistic regression. HPV DNA was detected in 44 (73.3%) of the 60 samples from immunodepressed patients and in 32 (53.3%) of the 60 samples from immunocompetent patients (adjusted odds ratio, 3.4; 95% CI, 1.2-9.6). In both groups of patients, HPV was more common in healthy perilesional skin than in lesional skin. HPV-β was the most common type isolated. We found a wide range of HPV types (mostly HPV-β) in the skin of kidney transplant recipients and immunocompetent patients with skin cancer. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

  18. 近12年中国民航人因事故与事故征候的分类研究%A Classification on Human Factor Accident/Incident of China Civil Aviation in Recent Twelve Years

    Institute of Scientific and Technical Information of China (English)

    罗晓利

    2004-01-01

    Objective To study human factor accident/incident occurred during 1990~2001 using new classification standard. Method The human factor accident/incident classification standard is developed on the basis of Reason's Model, combining with CAAC's traditional classifying method, and applied to the classified statistical analysis for 361 flying incidents and 35 flight accidents of China civil aviation, which is induced by human factors and occurred from 1990 to 2001. Result 1) the incident percentage of taxi and cruise is higher than that of takeoff, climb and descent. 2) The dominating type of flight incidents is diverging of runway, overrunning, near-miss, tail/wingtip/engine strike and ground obstacle impacting. 3) The top three accidents are out of control caused by crew, mountain collision and over runway. 4) Crew's basic operating skill is lower than what we imagined, the mostly representation is poor correcting ability when flight error happened. 5) Crew errors can be represented by incorrect control, regulation and procedure violation, disorientation and diverging percentage of correct flight level. Conclusion The poor CRM skill is the dominant factor impacting China civil aviation safety, this result has a coincidence with previous study, but there is much difference and distinct characteristic in top incident phase, the type of crew error and behavior performance compared with that of advanced countries. We should strengthen CRM training for all of pilots aiming at the Chinese pilot behavior characteristic in order to improve the safety level of China civil aviation.%目的对中国民航1990~2001年期间发生的人因事故征候和飞行事故进行分类研究.方法 运用Reason事故链模型,结合中国民航的传统分类方法,制订人因事故与事故征候分类标准,在此基础上按分类标准进行分类统计和分析.结果 1)在飞行的各个阶段中,滑行和巡航阶段小于间隔飞行的事故征候发生的百分比高于

  19. Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects

    DEFF Research Database (Denmark)

    Ottestad, Inger; Vogt, Gjermund; Retterstøl, Kjetil

    2012-01-01

    8-iso-PGF2a; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and a-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA þ DHA was observed in both fish oil groups, but no significant...... markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18–50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g...

  20. Long and Short Range Correlations in Healthy and Pathologic Human Cardiac Prosses

    Science.gov (United States)

    Bunde, Armin

    2001-03-01

    Healthy sleep consists of several stages: deep sleep, light sleep and REM sleep. In this talk, recent work on the characterization of heart-rates in the three stages by long-range correlations is presented. Only in REM sleep, long-range correlations reminiscent to the wake phase occur, and the heart-rates show multifractal behaviour. In contrast, in non-REM phases, the heart-rates are uncorrelated above the typical breathing cycle time, pointing to a random regulation of the heartbeat during non-REM sleep. In deep sleep, the heart-rates show simple multifractal behaviour.

  1. Viscoelastic properties of healthy human artery measured in saline solution by AFM based indentation technique

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, A.; Lilleodden, E.; Sickhaus, W.; Kinney, J.; Pruitt, L.; Balooch, M.

    1998-02-09

    Using an Atomic Force Microscope with an attachment for indentation, we have measured local, in vitro mechanical properties of healthy femoral artery tissue held in saline solution. The elastic modulus (34. 3 kPa) and viscoelastic response ({tau}sub{epsilon} {equals} 16.9 s and {tau}sub{sigma} {equals} 29.3 s) of the unstretched,intimal vessel wall have been determined using Sneddon theory and a three element model(standard linear solid) for viscoelastic materials. The procedures necessary to employ the indenting attachment to detect elastic moduli in the kPa range in liquid are described.

  2. The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota

    NARCIS (Netherlands)

    Scanlan, P.D.; Stensvold, C.R.; Rajilic-Stojanovic, M.; Heilig, H.G.; Vos, de W.M.; O'Toole, P.W.; Cotter, P.D.

    2014-01-01

    To date, the majority of research into the human gut microbiota has focused on the bacterial fraction of the community. Inevitably, this has resulted in a poor understanding of the diversity and functionality of other intestinal microorganisms in the human gut. One such nonbacterial member is the mi

  3. Hepatic Angiosarcoma: a Review of Twelve Cases

    Institute of Scientific and Technical Information of China (English)

    Qiang Li; Xishan Hao

    2005-01-01

    OBJECTIVE Hepatic angiosarcoma (HAS), a lethal disease, is the most common sarcoma arising in the liver. Little information about the epidemiology, etiology, diagnosis and management of HAS has been reported. Increased familiarity with this disease will facilitate correct diagnosis and help to improve management of this condition in the future.The objective of this study was to describe cases of hepatic angiosarcoma and to discuss the etiologic, diagnostic, therapeutic features and prognosis of this tumor. This report not only serves to give more evidence of the relationship between hepatic angiosarcoma and carcinogenic exposure, but also demonstrates the key points in different methods of diagnosis and the optimal treatment of hepatic angiosarcoma.METHODS Twelve cases of hepatic angiosareoma were analyzed retrospectively, representing the different character in clinical presentations and laboratory computed tomographical scans; pathological data and treatment are described. Clinical and biologic follow-up was carried out for two years after surgical treatment.RESULTS There were nine men and three women varying in ages from 57 to 71 years with an average of 64.3 years. Ten patientshad a history of exposure to vinyl chloride or thorotrast. Mild or moderate abdominal pain and bloating, abdominal mass and fever were the common clinical presentations. Tumors were visualized by ultrasonography and CT scans in all patients. Biochemical profiles yielded variable results and proved to be of little value in detection or diagnosis. Surgical resection was feasible for each patient who was treated as follows: two wedge resections, six segementectomies and four bisegmentectomies. Five patients received Neoadjuvant chemotherapy postoperatively. The survival rate of those cases was poor. The maximum survival time was fourteen months. The mean survival time for this chemotherapeutic group was 11 months. The difference between the survival time of those treated with an operation

  4. Screening of urocanic acid isomers in human basal and squamous cell carcinoma tumors compared with tumor periphery and healthy skin.

    Science.gov (United States)

    Decara, Juan Manuel; Aguilera, José; Abdala, Roberto; Sánchez, Purificación; Figueroa, Félix L; Herrera, Enrique

    2008-10-01

    Trans-urocanic acid is a major chromophore for ultraviolet (UV) radiation in human epidermis. The UV induces photoisomerization of trans-urocanic acid (tUCA) form to cis-urocanic acid (cUCA) and has been reported as an important mediator in the immunosuppression induced by UV. This immunomodulation has been recognized as an important factor related to skin cancer development. This is the first time that UCA isomers have been measured in epidermis of skin biopsies from patients with squamous cell carcinoma (SCC) and with basal cell carcinoma (BCC) and compared with the tumor periphery and biopsies of healthy photoexposed and non-photoexposed skin as controls. The UCA isomers were separated and quantified by high performance liquid chromatography. Analysis of UCA in healthy skin showed significant increase in total UCA content in non-photoexposed body sites compared with highly exposed skins. In contrast, the percentage of cUCA was higher in photoexposed body sites. Maximal levels of cUCA were found in cheek, forehead and forearm and lower levels in abdomen and thigh. No differences were found in total UCA concentration between the tumor samples and healthy photoexposed skin. However, differences were found in relation between isomers. Higher levels of cUCA were detected in SCC biopsies (44% of total UCA) compared with samples of BCC and that of healthy photoexposed skin (30%). These results suggest that the UV radiation exposure, a main factor in development of SCC can be mediated, apart from direct effect to cells (DNA damage), by immunosuppression pathways mediated by high production of cUCA.

  5. High-risk human papillomavirus (HPV screening and detection in healthy patient saliva samples: a pilot study

    Directory of Open Access Journals (Sweden)

    Wang Robert C

    2011-10-01

    Full Text Available Abstract Background The human papillomaviruses (HPV are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence. Methods Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity. Results Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (p Conclusions The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection.

  6. Two-photon autofluorescence lifetime and SHG imaging of healthy and diseased human corneas

    Science.gov (United States)

    Batista, Ana; Breunig, Hans Georg; Uchugonova, Aisada; Seitz, Berthold; Morgado, António Miguel; König, Karsten

    2015-03-01

    Corneal function can be drastically affected by several degenerations and dystrophies, leading to blindness. Early diagnosis of corneal disease is of major importance and it may be accomplished by monitoring changes of the metabolic state and structural organization, the first detectable pathological signs, by two-photon excitation autofluorescence lifetime and second-harmonic generation imaging. In this study, we propose to use these imaging techniques to differentiate between healthy and pathological corneas. Images were acquired using a laser-scanning microscope with a broadband sub-15 femtosecond near-infrared pulsed laser and a 16-channel photomultiplier tube detector for signal collection. This setup allows the simultaneous excitation of metabolic co-factors and to identify them based on their fluorescence spectra. We were able to discriminate between healthy and pathological corneas using two-photon excitation autofluorescence lifetime and second-harmonic generation imaging from corneal epithelium and stroma. Furthermore, differences between different pathologies were observed. Alterations in the metabolic state of corneal epithelial cells were observed using the autofluorescence lifetime of the metabolic co-factors. In the corneal stroma, we observed not only alterations in the collagen fibril structural organization but also alterations in the autofluorescence lifetime. Further tests are required as the number of pathological samples must be increased. In the future, we intend to establish a correlation between the metabolic and structural changes and the disease stage. This can be a step forward in achieving early diagnosis.

  7. The development of the corpus callosum in the healthy human brain.

    Science.gov (United States)

    Luders, Eileen; Thompson, Paul M; Toga, Arthur W

    2010-08-18

    The corpus callosum changes structurally throughout life, but most dramatically during childhood and adolescence. Even so, existing studies of callosal development tend to use parcellation schemes that may not capture the complex spatial profile of anatomical changes. Thus, more detailed mapping of callosal growth processes is desirable to create a normative reference. This will help to relate and interpret other structural, functional, and behavioral measurements, both from healthy subjects and pediatric patients. We applied computational surface-based mesh-modeling methods to analyze callosal morphology at extremely high spatial resolution. We mapped callosal development and explored sex differences in a large and well matched sample of healthy children and adolescents (n = 190) aged 5-18 years. Except for the rostrum in females, callosal thickness increased across the whole surface, with sex- and region-specific rates of growth, and at times shrinkage. The temporally distinct changes in callosal thickness are likely to be a consequence of varying degrees of axonal myelination, redirection, and pruning. Alternating phases of callosal growth and shrinkage may reflect a permanent adjustment and fine-tuning of fibers connecting homologous cortical areas during childhood and adolescence. Our findings emphasize the importance of taking into account sex differences in future studies, as existing developmental effects might remain disguised (or biased toward the effect of the dominant sex in unbalanced statistical designs) when pooling male and female samples.

  8. Interplay between the acute inflammatory response and heart rate variability in healthy human volunteers.

    Science.gov (United States)

    Kox, Matthijs; Ramakers, Bart P; Pompe, Jan C; van der Hoeven, Johannes G; Hoedemaekers, Cornelia W; Pickkers, Peter

    2011-08-01

    The autonomic nervous system and the inflammatory response are intimately linked. Heart rate variability (HRV) analysis is a widely used method to assess cardiac autonomic nervous system activity, and changes in HRV indices may correlate with inflammatory markers. Here, we investigated whether baseline HRV predicts the acute inflammatory response to endotoxin. Second, we investigated whether the magnitude of the inflammatory response correlated with HRV alterations. Forty healthy volunteers received a single intravenous bolus of 2 ng/kg endotoxin (LPS, derived from Escherichia coli O:113). Of these, 12 healthy volunteers were administered LPS again 2 weeks later. Heart rate variability was determined at baseline (just before LPS administration) and hourly thereafter until 8 h after LPS administration. Plasma cytokine levels were determined at various time points. Baseline HRV indices did not correlate with the magnitude of the LPS-induced inflammatory response. Despite large alterations in HRV after LPS administration, the extent of the inflammatory response did not correlate with the magnitude of HRV changes. In subjects who were administered LPS twice, inflammatory cytokines were markedly attenuated after the second LPS administration, whereas LPS-induced HRV alterations were similar. Heart rate variability indices do not predict the acute inflammatory response in a standardized model of systemic inflammation. Although the acute inflammatory response results in HRV changes, no correlations with inflammatory cytokines were observed. Therefore, the magnitude of endotoxemia-related HRV changes does not reflect the extent of the inflammatory response.

  9. spa typing and antimicrobial resistance of Staphylococcus aureus from healthy humans, pigs and dogs in Tanzania.

    Science.gov (United States)

    Katakweba, Abdul Sekemani; Muhairwa, Amandus Pachificus; Espinosa-Gongora, Carmen; Guardabassi, Luca; Mtambo, Madundo M A; Olsen, John Elmerdahl

    2016-02-28

    Staphylococcus aureus is an opportunistic pathogen causing infections in humans and animals. Here we report for the first time the prevalence of nasal carriage, spa typing and antimicrobial resistance of S. aureus in a Tanzanian livestock community. Nasal swabs were taken from 100 humans, 100 pigs and 100 dogs in Morogoro Municipal. Each swab was enriched in Mueller Hinton broth with 6.5% NaCl and subcultured on chromogenic agar for S. aureus detection. Presumptive S. aureus colonies were confirmed to the species level by nuc PCR and analysed by spa typing. Antimicrobial susceptibility patterns were determined by disc diffusion method. S. aureus was isolated from 22% of humans, 4% of pigs and 11% of dogs. A total of 21 spa types were identified: 13, 7 and 1 in human, dogs, and pigs, respectively. Three spa types (t314, t223 and t084) were shared between humans and dogs. A novel spa type (t10779) was identified in an isolate recovered from a colonized human. Antimicrobials tested revealed resistance to ampicillin in all isolates, moderate resistances to other antimicrobials with tetracycline resistance being the most frequent. S. aureus carrier frequencies in dogs and humans were within the expected range and low in pigs. The S. aureus spa types circulating in the community were generally not shared by different hosts and majority of types belonged to known clones. Besides ampicillin resistance, moderate levels of antimicrobial resistance were observed irrespective of the host species from which the strains were isolated.

  10. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans.

    Directory of Open Access Journals (Sweden)

    Margreet R Olthof

    2005-05-01

    Full Text Available BACKGROUND: Betaine (trimethylglycine lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans. METHODS AND FINDINGS: We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151, folic acid (two studies, n = 75, and phosphatidylcholine (one study, n = 26 on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25-0.46, and triacylglycerol concentrations by 0.14 mmol/l (0.04-0.23 relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14-0.32. Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06-0.21, but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d had no effect on lipid concentrations. CONCLUSIONS: Betaine supplementation increased blood LDL cholesterol and triacylglycerol

  11. Pulmonary capillary recruitment in response to hypoxia in healthy humans: a possible role for hypoxic pulmonary venoconstriction?

    DEFF Research Database (Denmark)

    Taylor, Bryan J; Kjaergaard, Jesper; Snyder, Eric M;

    2011-01-01

    capillary blood volume (Vc) were measured before and after saline infusion and hypoxic-exposure by a rebreathing method. Pulmonary artery systolic pressure (sPpa) and left ventricular (LV) diastolic function were assessed before and after hypoxic-exposure via echocardiography. Saline infusion increased Q......Ppa and LV diastolic function. In conclusion, hypoxia-induced pulmonary capillary recruitment in humans is only partly accounted for by changes in Q, sPpa and LV diastolic function. We speculate that hypoxic pulmonary venoconstriction may play a role in such recruitment.......We examined mechanisms by which hypoxia may elicit pulmonary capillary recruitment in humans. On separate occasions, twenty-five healthy adults underwent exposure to intravenous saline infusion (30 ml/kg ∼ 15 min) or 17-h normobaric hypoxia ( [FIO2 = 12.5%). Cardiac output (Q) and pulmonary...

  12. 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.

  13. Effects of dietary salt levels on monocytic cells and immune responses in healthy human subjects: a longitudinal study.

    Science.gov (United States)

    Yi, Buqing; Titze, Jens; Rykova, Marina; Feuerecker, Matthias; Vassilieva, Galina; Nichiporuk, Igor; Schelling, Gustav; Morukov, Boris; Choukèr, Alexander

    2015-07-01

    Increasing evidence indicated that excess salt consumption can impose risks on human health and a reduction in daily salt intake from the current average of approximately 12 g/d to 5-6 g/d was suggested by public health authorities. The studies on mice have revealed that sodium chloride plays a role in the modulation of the immune system and a high-salt diet can promote tissue inflammation and autoimmune disease. However, translational evidence of dietary salt on human immunity is scarce. We used an experimental approach of fixing salt intake of healthy human subjects at 12, 9, and 6 g/d for months and examined the relationship between salt-intake levels and changes in the immune system. Blood samples were taken from the end point of each salt intake period. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. We assessed immune function changes through the characterization of cytokine profiles in response to mitogen stimulation. The results showed that subjects on the high-salt diet of 12 g/d displayed a significantly higher number of immune cell monocytes compared with the same subjects on a lower-salt diet, and correlation test revealed a strong positive association between salt-intake levels and monocyte numbers. The decrease in salt intake was accompanied by reduced production of proinflammatory cytokines interleukin (IL)-6 and IL-23, along with enhanced producing ability of anti-inflammatory cytokine IL-10. These results suggest that in healthy humans high-salt diet has a potential to bring about excessive immune response, which can be damaging to immune homeostasis, and a reduction in habitual dietary salt intake may induce potentially beneficial immune alterations.

  14. Maximal heart rate does not limit cardiovascular capacity in healthy humans: insight from right atrial pacing during maximal exercise.

    Science.gov (United States)

    Munch, G D W; Svendsen, J H; Damsgaard, R; Secher, N H; González-Alonso, J; Mortensen, S P

    2014-01-15

    In humans, maximal aerobic power (VO2 max ) is associated with a plateau in cardiac output (Q), but the mechanisms regulating the interplay between maximal heart rate (HRmax) and stroke volume (SV) are unclear. To evaluate the effect of tachycardia and elevations in HRmax on cardiovascular function and capacity during maximal exercise in healthy humans, 12 young male cyclists performed incremental cycling and one-legged knee-extensor exercise (KEE) to exhaustion with and without right atrial pacing to increase HR. During control cycling, Q and leg blood flow increased up to 85% of maximal workload (WLmax) and remained unchanged until exhaustion. SV initially increased, plateaued and then decreased before exhaustion (P rate pressure product and RAP (P heart can be paced to a higher HR than observed during maximal exercise, suggesting that HRmax and myocardial work capacity do not limit VO2 max in healthy individuals. A limited left ventricular filling and possibly altered contractility reduce SV during atrial pacing, whereas a plateau in LVFP appears to restrict Q close to VO2 max .

  15. Correlation between the properties of the lipid matrix and the degrees of integrity and cohesion in healthy human Stratum corneum.

    Science.gov (United States)

    Berthaud, Fabienne; Boncheva, Mila

    2011-03-01

    The correlation between the degrees of integrity and cohesion in healthy human Stratum corneum (SC) and the properties of the SC lipid matrix could be examined non-invasively in vivo using ATR-FTIR spectroscopy and measurements of pH, conductance, and transepidermal water loss (TEWL) taken in the course of tape-stripping. The change of TEWL following the removal of a SC layer with a predefined thickness served as a measure for the SC integrity, and the amount of protein removed by predefined number of tapes - as a measure for the SC cohesion. The extent of lipids organized in orthorhombic lattices and the pH in the inner SC emerged as the main factors that determine the degree of integrity. The amounts and molecular organization of the SC lipids did not correlate with the degree of cohesion, while the pH and the hydration of SC correlated well with the degree of cohesion in the superficial but not in the inner SC layers. This study evidenced the variability of SC integrity and cohesion existing in healthy human skin, demonstrated the importance of the lipid molecular organization for the SC integrity, and illustrated the limitations in the determination the degree of corneodesmolysis in SC based only on the protein content of tape-strips.

  16. spa typing and antimicrobial resistance of Staphylococcus aureus from healthy humans, pigs and dogs in Tanzania

    DEFF Research Database (Denmark)

    Katakweba, Abdul S.; Muhairwa, Amandus P.; Espinosa-Gongora, Carmen

    2016-01-01

    Introduction: Staphylococcus aureus is an opportunistic pathogen causing infections in humans and animals. Here we report for the first time the prevalence of nasal carriage, spa typing and antimicrobial resistance of S. aureus in a Tanzanian livestock community. Methodology: Nasal swabs were taken...... from 100 humans, 100 pigs and 100 dogs in Morogoro Municipal. Each swab was enriched in Mueller Hinton broth with 6.5% NaCl and subcultured on chromogenic agar for S. aureus detection. Presumptive S. aureus colonies were confirmed to the species level by nuc PCR and analysed by spa typing....... Antimicrobial susceptibility patterns were determined by disc diffusion method. Results: S. aureus was isolated from 22 % of humans, 4 % of pigs and 11 % of dogs. A total of 21 spa types were identified: 13, 7 and 1 in human, dogs, and pigs, respectively. Three spa types (t314, t223 and t084) were shared...

  17. Effect of Tamarindus indica L. on the bioavailability of aspirin in healthy human volunteers.

    Science.gov (United States)

    Mustapha, A; Yakasai, I A; Aguye, I A

    1996-01-01

    The influence of Tamarindus indica L. fruit extract incorporated in a traditional meal on the bioavailability of aspirin tablets 600 mg dose was studied in 6 healthy volunteers. There was a statistically significant increase in the plasma levels of aspirin and salicylic acid, respectively, when the meal containing Tamarindus indica fruit extract was administered with the aspirin tablets than when taken under fasting state or with the meal without the fruit extract. The Cmax, AUC0-6h and t1/2 for aspirin increased from 10.04 +/- 0.1 mg/ml to 28.62 +/- 0.21 mg/ml (P Tamarindus indica L. fruit extract significantly increased the bioavailability of aspirin.

  18. Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers.

    Science.gov (United States)

    Simon, M; McClanahan, R H; Shah, J F; Repko, T; Modi, N B

    2005-08-01

    Pentosan polysulfate sodium (PPS) is the active ingredient in ELMIRON, a drug approved for the relief of bladder pain associated with interstitial cystitis. The study objective was to characterize the pharmacokinetic and metabolic profiles of PPS following oral dosing of [3H]PPS. As specific assays for PPS do not exist, metabolic profiling was accomplished through multiple fraction collections and radiochromatographic techniques. Two groups of eight healthy female subjects sequentially received a single oral dose of 200 microCi [3H]PPS supplemented with 300 mg unlabelled PPS or 300 microCi [3H]PPS supplemented with 450 mg unlabelled PPS. Most of the administered dose (84%) was excreted in faeces as intact PPS, and a smaller percentage (6%) was excreted in urine. In summary, orally administered PPS was very poorly absorbed, with the majority of the drug being excreted in faeces as intact PPS and in urine as low molecular weight and desulfated PPS.

  19. Leptin signaling in skeletal muscle after bed rest in healthy humans

    DEFF Research Database (Denmark)

    Guerra, Borja; Ponce-Gonzalez, Jesus Gustavo; Morales-Alamo, David

    2014-01-01

    PURPOSE: This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system. METHODS: Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m(2)) before and after 7 days of bed rest....... Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot. RESULTS: After bed rest basal insulin concentration.......4-fold after bed rest (P rest, as PTP1B in the deltoid. PTP1B was increased by 90% with bed rest in the vastus lateralis (P

  20. Unprecedented high insulin secretion in a healthy human subject after intravenous glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Knop, Filip K; Lund, Asger; Madsbad, Sten

    2014-01-01

    to as one of the most insulinotropic substances known. CASE PRESENTATION: Plasma insulin and C-peptide concentrations were measured in a healthy Caucasian male (age: 53 years; body mass index: 28.6 kg/m2; fasting plasma glucose: 5.7 mM; 2 h plasma glucose value following 75 g-oral glucose tolerance test: 3...... insulin and C-peptide responses were observed during meal test (peak concentrations: 300 and 3,278 pM) and glucagon test (peak concentrations: 250 and 2,483 pM). During the hyperglycaemic clamp with continuous intravenous infusion of GLP-1 the subject exhibited plasma insulin and C-peptide concentrations...

  1. Investigation on the load-deformation curves of a human healthy heel pad

    DEFF Research Database (Denmark)

    Fontanella, C. G.; Matteoli, Sara; Carniel, E.L.;

    2012-01-01

    . A 30 year-old European healthy female (mass=54kg, height=165cm) was enrolled in this study. Her left foot underwent both MRI and compression tests. A numerical model of the heel region was developed based on a 3D CAD solid model obtained by MR images. The calcaneal fat pad tissue was described...... with a visco-hyperelastic model, while a fiber-reinforced hyperelastic model was formulated for the skin. Numerical analyses were performed to interpret the mechanical response of heel tissues. Different loading conditions were assumed according to experimental tests. The heel tissues showed a non-linear visco...... and 0.25±0.01 at high strain rate). The validity and efficacy of the investigation performed was confirmed by the interpretation of the mechanical response of the heel tissues under different strain rates. The mean absolute percentage error between experimental data and model results was 0.39% at low...

  2. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects.

    Science.gov (United States)

    Gregory, Jesse F; Park, Youngja; Lamers, Yvonne; Bandyopadhyay, Nirmalya; Chi, Yueh-Yun; Lee, Kichen; Kim, Steven; da Silva, Vanessa; Hove, Nikolas; Ranka, Sanjay; Kahveci, Tamer; Muller, Keith E; Stevens, Robert D; Newgard, Christopher B; Stacpoole, Peter W; Jones, Dean P

    2013-01-01

    Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5'-phosphate (PLP) serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23) were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD) to 21.5±4.6 nmol/L (Pamino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.

  3. Healthy aging attenuates task-related specialization in the human medial temporal lobe

    DEFF Research Database (Denmark)

    Ramsøy, Thomas Z.; Liptrot, Matthew George; Skimminge, Arnold Jesper Møller

    2012-01-01

    hemisphere were defined as ROIs. Aging had an adverse effect on memory performance that was similar for memorizing objects or positions. In left and right MTL, relatively greater activation for object stimuli was attenuated in older individuals. Age-related attenuation in content specificity was most...... prominent in the recognition stage. During recognition, the larger response to objects gradually decreased with age in all ROIs apart from left temporopolar and entorhinal cortex. An age-related attenuation was also present during encoding, but only in right parahippocampus and amygdala. Our results suggest...... conflicting findings. Using functional magnetic resonance imaging (fMRI), we have recently shown that young healthy individuals show a stronger activation of the MTL during encoding of objects as compared with encoding of positions. Using the same encoding task, the present study addressed the question...

  4. Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage

    DEFF Research Database (Denmark)

    Heinemeier, Katja M.; Schjerling, Peter; Heinemeier, Jan

    2016-01-01

    The poor regenerative capacity of articular cartilage presents a major clinical challenge and may relate to a limited turnover of the cartilage collagen matrix. However, the collagen turnover rate during life is not clear, and it is debated whether osteoarthritis (OA) can influence it. Using...... the carbon-14 ((14)C) bomb-pulse method, life-long replacement rates of collagen were measured in tibial plateau cartilage from 23 persons born between 1935 and1997 (15 and 8 persons with OA and healthy cartilage, respectively). The (14)C levels observed in cartilage collagen showed that, virtually......, no replacement of the collagen matrix happened after skeletal maturity and that neither OA nor tissue damage, per se, influenced collagen turnover. Regional differences in (14)C content across the joint surface showed that cartilage collagen located centrally on the joint surface is formed several years earlier...

  5. Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans

    Directory of Open Access Journals (Sweden)

    Farzaneh A Sorond

    2008-04-01

    Full Text Available Farzaneh A Sorond1,2, Lewis A Lipsitz2,4, Norman K Hollenberg3,5, Naomi DL Fisher31Department of Neurology, Stroke Division; 2Institute for Aging Research, Hebrew SeniorLife, Boston, MA; 3Department of Medicine, Endocrine-Hypertension Division; 4Department of Medicine, Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, USA; 5Department of Radiology, Brigham and Women’s Hospital, Boston, MABackground and Purpose: Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC consumption on cerebral blood flow in older healthy volunteers.Methods: We used transcranial Doppler (TCD ultrasound to measure mean blood flow velocity (MFV in the middle cerebral artery (MCA in thirty-four healthy elderly volunteers (72 ± 6 years in response to the regular intake of FRC or flavanol-poor cocoa (FPC.Results: In response to two weeks of FRC intake, MFV increased by 8% ± 4% at one week (p = 0.01 and 10% ± 4% (p = 0.04 at two weeks. In response to one week of cocoa, significantly more subjects in the FRC as compared with the FPC group had an increase in their MFV (p < 0.05.Conclusions: In summary, we show that dietary intake of FRC is associated with a significant increase in cerebral blood flow velocity in the MCA as measured by TCD. Our data suggest a promising role for regular cocoa flavanol’s consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke.Keywords: cerebral blood flow, flavanol, cocoa, transcranial Doppler ultrasound

  6. Interleukin 1-beta analysis in chronically inflamed and healthy human dental pulp

    Directory of Open Access Journals (Sweden)

    Šubarić Ljiljana

    2017-01-01

    Full Text Available Background/Aim. Proinflammatory cytokines can act like endogenous pyrogen interleukin 1 (IL-1, interleukin 6 (IL-6 and tumour necrosis factor alpha (TNF α which regulate the synthesis of secondary mediators and other proinflammatory cytokines through macrophages and mesenchymal cells. They stimulate acute-phase proteins and attract inflammatory cells. The aim of this study was to determine interleukin 1-β (IL-1 β concentrations in chronically inflamed and healthy dental pulps. Methods. A total of 41 pulps (19 from patients with pulpitis chronic causa and 22 from patients with pulpatis chronic aperta, divided into two groups, were obtained from teeth with chronic pulp inflammation. The control group consisted of 12 teeth with healthy pulp. After extirpation, pulp samples were immediately placed in sterile Eppendorf tubes and frozen. After that, homogenisation was performed by a Teflon® pestle in ice-cold phosphate buffer solution at pH 7.4 whose volume was adjusted according to the weight of tissue. The supernatant was then frozen at -70°C until the performance of appropriate biochemical analyses. Cytokine IL-1 β value was determined by a commercial enzyme- linked immunosorbent assay (ELISA test. We applied the high sensitivity system technique, which may register low levels of cytokines, ranging from 0.125 to 8.0 pg/mL for IL-1 β. Results. By comparing the mean value of IL-1β, in the pulps we can see a statistically significant difference (p < 0.01 among them. The highest value of IL-1 β was in the subjects with pulpitis chronica clausa and it was 6.21 ± 2.70 pg/mL. Conclusion. Proinflammatory cytokine IL-1 β is present in detectable quantities in the pulp tissue of all vital pulps. Its highest concentrations were found in the sample group with pulpitis chronica clausa.

  7. Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects.

    Science.gov (United States)

    Al-Jenoobi, Fahad Ibrahim; Al-Thukair, Areej A; Alam, Mohd Aftab; Abbas, Fawkeya A; Al-Mohizea, Abdullah M; Alkharfy, Khalid M; Al-Suwayeh, Saleh A

    2015-03-01

    Effect of Curcuma longa rhizome powder and its ethanolic extract on CYP2D6 and CYP3A4 metabolic activity was investigated in vitro using human liver microsomes and clinically in healthy human subjects. Dextromethorphan (DEX) was used as common probe for CYP2D6 and CYP3A4 enzymes. Metabolic activity of CYP2D6 and CYP3A4 was evaluated through in vitro study; where microsomes were incubated with NADPH in presence and absence of Curcuma extract. In clinical study phase-I, six healthy human subjects received a single dose (30 mg) of DEX syrup, and in phase-II DEX syrup was administered with Curcuma powder. The enzyme CYP2D6 and CYP3A4 mediated O- and N-demethylation of dextromethorphan into dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. Curcuma extract significantly inhibited the formation of DOR and 3-MM, in a dose-dependent and linear fashion. The 100 μg/ml dose of curcuma extract produced highest inhibition, which was about 70 % for DOR and 80 % for 3-MM. Curcuma significantly increases the urine metabolic ratio of DEX/DOR but the change in DEX/3-MM ratio was statistically insignificant. Present findings suggested that curcuma significantly inhibits the activity of CYP2D6 in in vitro as well as in vivo; which indicates that curcuma has potential to interact with CYP2D6 substrates.

  8. Twelve years of Neandertal genetic discoveries

    DEFF Research Database (Denmark)

    Orlando, Ludovic Antoine Alexandre; Hänni, Catherine

    2011-01-01

    specimens have delivered authentic mitochondrial sequences. This information has helped us to better understand the evolution of the Neandertal gene pool over space and time and to address the long-standing question of possible admixture with their modern human relatives. This chapter reviews current...

  9. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders.

    Science.gov (United States)

    Ye, Zhaohui; Zhan, Huichun; Mali, Prashant; Dowey, Sarah; Williams, Donna M; Jang, Yoon-Young; Dang, Chi V; Spivak, Jerry L; Moliterno, Alison R; Cheng, Linzhao

    2009-12-24

    Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS cell lines were generated from previously frozen cord blood or adult CD34(+) cells of healthy donors, and could be redirected to hematopoietic differentiation. Multiple iPS cell lines were also generated from peripheral blood CD34(+) cells of 2 patients with myeloproliferative disorders (MPDs) who acquired the JAK2-V617F somatic mutation in their blood cells. The MPD-derived iPS cells containing the mutation appeared normal in phenotypes, karyotype, and pluripotency. After directed hematopoietic differentiation, the MPD-iPS cell-derived hematopoietic progenitor (CD34(+)CD45(+)) cells showed the increased erythropoiesis and gene expression of specific genes, recapitulating features of the primary CD34(+) cells of the corresponding patient from whom the iPS cells were derived. These iPS cells provide a renewable cell source and a prospective hematopoiesis model for investigating MPD pathogenesis.

  10. Effects of pregnancy, obesity and aging on the intensity of perceived breathlessness during exercise in healthy humans.

    Science.gov (United States)

    Jensen, Dennis; Ofir, Dror; O'Donnell, Denis E

    2009-05-30

    The healthy human respiratory system has impressive ventilatory reserve and can easily meet the demands placed upon it by strenuous exercise. Several acute physiological adaptations during exercise ensure harmonious neuromechanical coupling of the respiratory system, which allow healthy humans to reach high levels of ventilation without perceiving undue respiratory discomfort (breathlessness). However, in certain circumstances, such as pregnancy, obesity and natural aging, ventilatory reserve becomes diminished and exertional breathlessness is present. In this review, we focus on what is known about the mechanisms of increased activity-related breathlessness in these populations. Notwithstanding the obvious physiological differences between the three conditions, they share some common perceptual and ventilatory responses to exercise. Breathlessness intensity ratings (described as an increased "sense of effort") are consistently higher than normal at any given submaximal power output; and central motor drive to the respiratory muscles is consistently increased, reflecting increased ventilatory stimulation. The increased contractile respiratory muscle effort required to support the increased ventilatory requirements of exercise remains the most plausible source of increased activity-related breathlessness in pregnant, obese and elderly humans. In all three conditions, static and dynamic respiratory mechanical/muscular function is, to some extent, altered or impaired. Nevertheless, breathlessness intensity ratings are not significantly increased (compared to normal) at any given exercise ventilation in any of these three conditions. This strongly suggests that respiratory mechanical/muscular factors, per se, may be less important in the genesis of breathlessness. Moreover, in pregnancy and obesity, we present evidence that effective physiological adjustments exist to counterbalance the potentially negative sensory consequences of the altered respiratory mechanical

  11. Twelve tips on teaching and learning humanism in medical education.

    Science.gov (United States)

    Cohen, Libby Gordon; Sherif, Youmna Ashraf

    2014-08-01

    The teaching of humanistic values is recognized as an essential component of medical education and continuing professional development of physicians. The application of humanistic values in medical care can benefit medical students, clinicians and patients. This article presents 12 tips on fostering humanistic values in medical education. The authors reviewed the literature and present 12 practical tips that are relevant to contemporary practices. The tips can be used in teaching and sustaining humanistic values in medical education. Humanistic values can be incorporated in formal preclinical environments, the transition into clinical settings, medical curricula and clinical clerkships. Additionally, steps can be taken so that medical educators and institutions promote and sustain humanistic values.

  12. Serum vitamin D levels are not altered after controlled diesel exhaust exposures in healthy human subjects

    Science.gov (United States)

    Past research has suggested that exposure to urban air pollution may be associated with vitamin D deficiency in human populations. Vitamin D is widely known for its importance in bone growth/remodeling, muscle metabolism, and its ability to promote calcium absorption in the gut; ...

  13. Individual Differences in Spatial Pattern Separation Performance Associated with Healthy Aging in Humans

    Science.gov (United States)

    Stark, Shauna M.; Yassa, Michael A.; Stark, Craig E. L.

    2010-01-01

    Rodent studies have suggested that "pattern separation," the ability to distinguish among similar experiences, is diminished in a subset of aged rats. We extended these findings to the human using a task designed to assess spatial pattern separation behavior (determining at time of test whether pairs of pictures shown during the study were in the…

  14. Characterization of DTI Indices in the Cervical, Thoracic, and Lumbar Spinal Cord in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Rachael L. Bosma

    2012-01-01

    Full Text Available The aim of this study was to characterize in vivo measurements of diffusion along the length of the entire healthy spinal cord and to compare DTI indices, including fractional anisotropy (FA and mean diffusivity (MD, between cord regions. The objective is to determine whether or not there are significant differences in DTI indices along the cord that must be considered for future applications of characterizing the effects of injury or disease. A cardiac gated, single-shot EPI sequence was used to acquire diffusion-weighted images of the cervical, thoracic, and lumbar regions of the spinal cord in nine neurologically intact subjects (19 to 22 years. For each cord section, FA versus MD values were plotted, and a k-means clustering method was applied to partition the data according to tissue properties. FA and MD values from both white matter (average FA=0.69, average MD=0.93 × 10−3 mm2/s and grey matter (average FA=0.44, average MD=1.8 × 10−3 mm2/s were relatively consistent along the length of the cord.

  15. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects.

    Science.gov (United States)

    Lee, Go-Eun; Yun, Jong-Min; Yang, Seung-Bum; Kang, Yeonseok; Kang, Hyung-Won; Choi, Kwang-Ho; Kim, Junbeom; Kwon, O Sang; Park, Ji-Eun; Kim, Jae-Hyo

    2017-01-01

    The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7). The electroencephalogram (EEG) signals from nine healthy young subjects were recorded before and during acupuncture in the "closed-eye" state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2). Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6) and occipital areas (O1, O2) during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5) and other areas (frontal, parietal, and occipital). Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS).

  16. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Go-Eun Lee

    2017-01-01

    Full Text Available The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7. The electroencephalogram (EEG signals from nine healthy young subjects were recorded before and during acupuncture in the “closed-eye” state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2. Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6 and occipital areas (O1, O2 during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5 and other areas (frontal, parietal, and occipital. Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS.

  17. The microbiological signature of human cutaneous leishmaniasis lesions exhibits restricted bacterial diversity compared to healthy skin

    Science.gov (United States)

    Salgado, Vanessa R; de Queiroz, Artur TL; Sanabani, Sabri S; de Oliveira, Camila I; Carvalho, Edgar M; Costa, Jackson ML; Barral-Netto, Manoel; Barral, Aldina

    2016-01-01

    Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions. PMID:27074253

  18. Insulin, catecholamines, glucose and antioxidant enzymes in oxidative damage during different loads in healthy humans.

    Science.gov (United States)

    Koska, J; Blazícek, P; Marko, M; Grna, J D; Kvetnanský, R; Vigas, M

    2000-01-01

    Exercise, insulin-induced hypoglycemia and oral glucose loads (50 g and 100 g) were used to compare the production of malondialdehyde and the activity of antioxidant enzymes in healthy subjects. Twenty male volunteers participated in the study. Exercise consisted of three consecutive work loads on a bicycle ergometer of graded intensity (1.5, 2.0, and 2.5 W/kg, 6 min each). Hypoglycemia was induced by insulin (Actrapid MC Novo, 0.1 IU/kg, i.v.). Oral administration of 50 g and 100 g of glucose was given to elevate plasma glucose. The activity of superoxide dismutase (SOD) was determined in red blood cells, whereas glutathione peroxidase (GSH-Px) activity was measured in whole blood. The concentration of malondialdehyde (MDA) was determined by HPLC, catecholamines were assessed radioenzymatically and glucose was measured by the glucose-oxidase method. Exercise increased MDA concentrations, GSH-Px and SOD activities as well as plasma noradrenaline and adrenaline levels. Insulin hypoglycemia increased plasma adrenaline levels, but the concentrations of MDA and the activities of GSH-Px and SOD were decreased. Hyperglycemia increased plasma MDA concentrations, but the activities of GSH-Px and SOD were significantly higher after a larger dose of glucose only. Plasma catecholamines were unchanged. These results indicate that the transient increase of plasma catecholamine and insulin concentrations did not induce oxidative damage, while glucose already in the low dose was an important triggering factor for oxidative stress.

  19. Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

    Science.gov (United States)

    Newman, S; Malik, S; Hirst, R; Pitcairn, G; Heide, A; Pabst, J; Dinkelaker, A; Fleischer, W

    2002-12-01

    The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.

  20. Genotype and ancestry modulate brain's DAT availability in healthy humans

    Energy Technology Data Exchange (ETDEWEB)

    Shumay, E.; Shumay, E.; Chen, J.; Fowler, J.S.; Volkow, N.D.

    2011-08-01

    The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [{sup 11}C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: (1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; (2) ethnic background and age influence the strength of these associations; and (3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.

  1. Analysis of the association between host genetics, smoking, and sputum microbiota in healthy humans.

    Science.gov (United States)

    Lim, Mi Young; Yoon, Hyo Shin; Rho, Mina; Sung, Joohon; Song, Yun-Mi; Lee, Kayoung; Ko, GwangPyo

    2016-03-31

    Recent studies showing clear differences in the airway microbiota between healthy and diseased individuals shed light on the importance of the airway microbiota in health. Here, we report the associations of host genetics and lifestyles such as smoking, alcohol consumption, and physical activity with the composition of the sputum microbiota using 16S rRNA gene sequence data generated from 257 sputum samples of Korean twin-family cohort. By estimating the heritability of each microbial taxon, we found that several taxa, including Providencia and Bacteroides, were significantly influenced by host genetic factors. Smoking had the strongest effect on the overall microbial community structure among the tested lifestyle factors. The abundances of Veillonella and Megasphaera were higher in current-smokers, and increased with the pack-year value and the Fagerstrom Test of Nicotine Dependence (FTND) score. In contrast, Haemophilus decreased with the pack-year of smoking and the FTND score. Co-occurrence network analysis showed that the taxa were clustered according to the direction of associations with smoking, and that the taxa influenced by host genetics were found together. These results demonstrate that the relationships among sputum microbial taxa are closely associated with not only smoking but also host genetics.

  2. Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.

    Directory of Open Access Journals (Sweden)

    Sandi L Navarro

    Full Text Available Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans.We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d plus chondroitin sulfate (1200 mg/d for 28 days compared to placebo in 18 (9 men, 9 women healthy, overweight (body mass index 25.0-32.5 kg/m2 adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP, interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin.Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048. There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16, after glucosamine and chondroitin compared to placebo.Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer.ClinicalTrials.gov NCT01682694.

  3. Intergenerational Efforts to Develop a Healthy Environment for Everyone: Sustainability as a Human Rights Issue.

    Science.gov (United States)

    Kruger, Tina M; Savage, Caroline E; Newsham, Patrick

    2014-12-01

    As climate change proceeds at an unprecedented rate, concern for the natural environment has increased. The world's population aging also continues to rise at an unprecedented rate, giving greater attention to the implications of an older population. The two trends are linked through the fact that changes to the environment affect older adults, and older adults affect the environment. Sustainability is, therefore, an intergenerational phenomenon, and protecting resources today leaves a positive legacy and enhances quality of life for future generations. Older adults have much to share with younger generations about behaviors that promote sustainable living, yet few sustainability efforts are intergenerational in nature. As large numbers of people currently subsist without secure access to basic needs, ensuring equitable resource consumption for all generations is urgent and aligns with the Universal Declaration of Human Rights. Through exploring linkages between aging and sustainability, we identify intergenerational strategies to protect the environment and promote human rights and quality of life for older adults.

  4. TAILS N-terminomic and proteomic datasets of healthy human dental pulp.

    Science.gov (United States)

    Eckhard, Ulrich; Marino, Giada; Abbey, Simon R; Matthew, Ian; Overall, Christopher M

    2015-12-01

    The Data described here provide the in depth proteomic assessment of the human dental pulp proteome and N-terminome (Eckhard et al., 2015) [1]. A total of 9 human dental pulps were processed and analyzed by the positional proteomics technique TAILS (Terminal Amine Isotopic Labeling of Substrates) N-terminomics. 38 liquid chromatography tandem mass spectrometry (LC-MS/MS) datasets were collected and analyzed using four database search engines in combination with statistical downstream evaluation, to yield the by far largest proteomic and N-terminomic dataset of any dental tissue to date. The raw mass spectrometry data and the corresponding metadata have been deposited in ProteomeXchange with the PXD identifier ; Supplementary Tables described in this article are available via Mendeley Data (10.17632/555j3kk4sw.1).

  5. TAILS N-terminomic and proteomic datasets of healthy human dental pulp

    Directory of Open Access Journals (Sweden)

    Ulrich Eckhard

    2015-12-01

    Full Text Available The Data described here provide the in depth proteomic assessment of the human dental pulp proteome and N-terminome (Eckhard et al., 2015 [1]. A total of 9 human dental pulps were processed and analyzed by the positional proteomics technique TAILS (Terminal Amine Isotopic Labeling of Substrates N-terminomics. 38 liquid chromatography tandem mass spectrometry (LC-MS/MS datasets were collected and analyzed using four database search engines in combination with statistical downstream evaluation, to yield the by far largest proteomic and N-terminomic dataset of any dental tissue to date. The raw mass spectrometry data and the corresponding metadata have been deposited in ProteomeXchange with the PXD identifier ; Supplementary Tables described in this article are available via Mendeley Data (10.17632/555j3kk4sw.1.

  6. Study of OH● Radicals in Human Serum Blood of Healthy Individuals and Those with Pathological Schizophrenia

    OpenAIRE

    2011-01-01

    The human body is constantly under attack from free radicals that occur as part of normal cell metabolism, and by exposure to environmental factors such as UV light, cigarette smoke, environmental pollutants and gamma radiation. The resulting “Reactive Oxygen Species” (ROS) circulate freely in the body with access to all organs and tissues, which can have serious repercussions throughout the body. The body possesses a number of mechanisms both to control the production of ROS and to cope with...

  7. Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants

    OpenAIRE

    2014-01-01

    Humans are naturally inquisitive. This tendency is adaptive, aiding identification of potentially valuable novel outcomes. The dopaminergic substantia nigra (SN) is implicated in the drive to explore novel stimuli and situations. However, infection and inflammation inhibit the motivation to seek out novelty. This likely serves to limit exposure to uncertain, potentially detrimental outcomes when metabolic resources are limited. Nevertheless, the neural mechanisms through which inflammation co...

  8. Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers.

    Science.gov (United States)

    Hougee, Sander; Faber, Joyce; Sanders, Annemarie; de Jong, Romy B; van den Berg, Wim B; Garssen, Johan; Hoijer, Maarten A; Smit, H Friso

    2005-05-01

    In this study, an extract of Pterocarpus marsupium Roxb. containing pterostilbene has been evaluated for its PGE2-inhibitory activity in LPS-stimulated PBMC. In addition, the COX-1/2 selective inhibitory activity of P. marsupium (PM) extract was investigated. Biological activity, as well as safety of PM extract was evaluated in healthy human volunteers. PM extract, pterostilbene and resveratrol inhibited PGE2 production from LPS-stimulated human peripheral blood mononuclear cells (PBMC) with IC50 values of 3.2 +/- 1.3 microg/mL, 1.0 +/- 0.6 microM and 3.2 +/- 1.4 microM, respectively. When pterostilbene content of PM extract is calculated, PGE2 production inhibition of PM extract is comparable to PGE2 production inhibition of purified pterostilbene. Furthermore, in a COX-1 whole blood assay (WBA) PM extract was not effective while in a COX-2 WBA, PM extract decreased PGE2 production indicating COX-2 specific inhibition. In healthy human volunteers, the oral use of 450 mg PM extract did not decrease PGE2 production ex vivo in a WBA. Pterostilbene levels in serum were increased, but were 5-fold lower than the observed IC50 for PGE2 inhibition in LPS-stimulated PBMC. No changes from base-line of the safety parameters were observed and no extract-related adverse events occurred during the study. In conclusion, this is the first study to describe the selective COX-2 inhibitory activity of a Pterocarpus marsupium extract. Moreover, the PGE2 inhibitory activity of PM extract was related to its pterostilbene content. In humans, 450 mg PM extract resulted in elevated pterostilbene levels in serum, which were below the active concentration observed in vitro. In addition, short-term supplementation of 450 mg PM extract is considered to be a safe dose based on the long history of use, the absence of abnormal blood cell counts and blood chemistry values and the absence of extract-related adverse events. This strongly argues for a dose-finding study of PM extract in humans to

  9. Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

    Energy Technology Data Exchange (ETDEWEB)

    Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Oshita, Masatoshi; Ideno, Shoji [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Yunoki, Mikihiro [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Kuhara, Motoki [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano 396-0002 (Japan); Yamamoto, Naomasa [Department of Biochemistry, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963-8611 (Japan); Okuno, Yoshinobu [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa 768-0061 (Japan); Ikuta, Kazuyoshi, E-mail: ikuta@biken.osaka-u.ac.jp [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan)

    2009-09-11

    Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.

  10. Innate and adaptive immune interactions at the fetal-maternal interface in healthy human pregnancy and preeclampsia

    Directory of Open Access Journals (Sweden)

    Peter eHsu

    2014-03-01

    Full Text Available Maternal immune tolerance of the fetus is indispensible for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface – the decidua, the site of implantation and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, preeclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3+ regulatory T (Treg cells are crucial for ensuring immune tolerance towards the semi-allogeneic fetus. Additionally, another population of CD4+HLA-G+ suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy.

  11. Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans

    Science.gov (United States)

    de la Salle, Sara; Choueiry, Joelle; Shah, Dhrasti; Bowers, Hayley; McIntosh, Judy; Ilivitsky, Vadim; Knott, Verner

    2016-01-01

    N-methyl-D-aspartate (NMDA) receptor antagonists administered to healthy humans results in schizophrenia-like symptoms, which preclinical research suggests are due to glutamatergically altered brain oscillations. Here, we examined resting-state electroencephalographic activity in 21 healthy volunteers assessed in a placebo-controlled, double-blind, randomized study involving administration of either a saline infusion or a sub-anesthetic dose of ketamine, an NMDA receptor antagonist. Frequency-specific current source density (CSD) was assessed at sensor-level and source-level using eLORETA within regions of interest of a triple network model of schizophrenia (this model posits a dysfunctional switching between large-scale Default Mode and Central Executive networks by the monitor-controlling Salience Network). These CSDs were measured in each session along with subjective symptoms as indexed with the Clinician Administered Dissociative States Scale. Ketamine-induced CSD reductions in slow (delta/theta and alpha) and increases in fast (gamma) frequencies at scalp electrode sites were paralleled by frequency-specific CSD changes in the Default Mode, Central Executive, and Salience networks. Subjective symptoms scores were increased with ketamine and ratings of depersonalization in particular were associated with alpha CSD reductions in general and in specific regions of interest in each of the three networks. These results tentatively support the hypothesis that pathological brain oscillations associated with hypofunctional NMDA receptor activity may contribute to the emergence of the perceptual/dissociate symptoms of schizophrenia. PMID:27729865

  12. Electromyography of Swallowing with Fine Wire Intramuscular Electrodes in Healthy Human: Amplitude Difference of Selected Hyoid Muscles.

    Science.gov (United States)

    Inokuchi, Haruhi; González-Fernández, Marlís; Matsuo, Koichiro; Brodsky, Martin B; Yoda, Mitsumasa; Taniguchi, Hiroshige; Okazaki, Hideto; Hiraoka, Takashi; Palmer, Jeffrey B

    2016-02-01

    Few studies have examined the intensity of muscle activity during swallowing in healthy humans. We examined selected hyoid muscles using fine wire intramuscular electromyography (EMG) during swallowing of four food consistencies. Thirteen healthy adults were studied using videofluorography and EMG of the anterior belly of digastric (ABD), geniohyoid (GH), sternohyoid (SH), and masseter (MA; surface electrodes) while ingesting thin liquid (three trials) and solid food of three consistencies (banana, tofu, and cookie, three trials each). After rectification, integration, and normalization, peak EMG amplitudes for each muscle in each trial were measured. Hyoid displacements were measured in two dimensions. Data were analyzed using repeated measures ANOVA with Bonferroni correction. GH had the highest adjusted amplitude for both solids and liquid. For MA and ABD, amplitude was highest with triturated cookie. For ABD, amplitude was lowest with liquid. There were no significant food consistency effects for GH or SH. Hyoid displacements were greatest for cookie and the lowest for liquid. EMG amplitude varied with initial food consistency. The high peak EMG amplitude of GH is consistent with its essential role in opening the upper esophageal sphincter. High MA amplitude with hard solid foods is likely due to the higher tongue-palate pressure with triturated solids. The higher ABD amplitude with solid food is associated with greater hyoid displacement. These findings support the existence of a central pattern generator that modifies the level of muscle activity during pharyngeal swallowing in response to input from mechanoreceptors in the oral cavity.

  13. Binocular Symmetry/Asymmetry of Scleral Redness as a Cue for Sadness, Healthiness, and Attractiveness in Humans

    Directory of Open Access Journals (Sweden)

    Robert R. Provine

    2013-10-01

    Full Text Available Among primates, only humans have the white sclerae that provide the ground necessary to display their own color and that of the overlying conjunctiva. Scleral color, primarily redness, provides cues of socially and biologically significant information about an individual. The present study examines the effect of the asymmetry of binocular scleral redness on perceived sadness, healthiness, and attractiveness by contrasting ratings of images of individuals who had one, both, or neither sclera reddened by digital editing. Building upon previous research, this study further defines the details of the scleral color display and contributes to the more general issue of facial and body symmetry, predictors of phenotypic condition and genotypic quality that are of interest to evolutionary theorists. Individuals with binocular and monocular redness were rated as sadder, less healthy, and less attractive than those with untinted control sclerae, with ratings corresponding to the degree of redness or whiteness. Bilaterally symmetrical (binocular scleral redness or whiteness provided anchorage points for ratings, with ratings for bilaterally asymmetrical (monocular redness or whiteness falling between them; there was no unique effect of asymmetry.

  14. Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans

    Energy Technology Data Exchange (ETDEWEB)

    Prior, John O.; Schindler, Thomas H.; Facta, Alvaro D.; Hernandez-Pampaloni, Miguel; Campisi, Roxana; Dahlbom, Magnus; Schelbert, Heinrich R. [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, B2-085J CHS, 10833 Le Conte Ave, Box 956948, Los Angeles, CA (United States)

    2007-01-15

    Response of myocardial blood flow (MBF) to sympathetic stimulation with cold is modulated by endothelium-related factors and is typically altered in the presence of coronary risk factors. Determinants of flow response to cold pressor testing (CPT) in normal volunteers at low risk for CAD remain less well defined, especially relative to baseline conditions such as hemodynamics and MBF, plasma substrate and lipid levels, and total pharmacologically stimulated vasodilator capacity. In 50 normal volunteers (42{+-}13 years; 31 women) without coronary risk factors, insulin resistance, or family history of diabetes/premature CAD, MBF was measured with {sup 13}N-ammonia and PET at baseline, during CPT, and during pharmacologic hyperemia. Sympathetic stimulation with CPT raised heart rate and blood pressure and thus MBF ({delta}MBF=0.23{+-}0.09 ml/min/g). MBF response, defined in absolute flow units as the difference between CPT and baseline, was independent of age, gender, heart rate, and blood pressure and rate-pressure product (RPP) at baseline as well as plasma substrate and lipid levels with the exception of an association with HDL cholesterol ({rho}=0.40, p=0.005) but depended on the change in RPP from rest ({rho}=0.33, p=0.019). Finally, changes in coronary vascular resistance in response to CPT were associated with changes in pharmacologic vasodilation ({rho}=0.56, p<0.0001). MBF response to sympathetic stimulation with cold (NO-mediated endothelium-dependent vasomotion), reflecting the functional state of the coronary endothelium, was independent of gender, age, and resting heart conditions. It was modulated by HDL cholesterol levels, even in healthy volunteers, and also related to pharmacologically stimulated vasodilator capacity at the coronary vascular resistance level. (orig.)

  15. Immunomodulatory effects of a standardized Lycium barbarum fruit juice in Chinese older healthy human subjects.

    Science.gov (United States)

    Amagase, Harunobu; Sun, Bixuang; Nance, Dwight M

    2009-10-01

    Lycium barbarum has been traditionally used in combination with several herbs for medicinal properties, but systematic modern clinical evaluation as a single herb has not been reported. To examine the systematic effects of L. barbarum on immune function, general well-being, and safety, we tested the effects of a standardized L. barbarum fruit juice (GoChi, FreeLife International, Phoenix, AZ, USA) at 120 mL/day, equivalent to at least 150 g of fresh fruit, the amount traditionally used, or placebo for 30 days in a randomized, double-blind, placebo-controlled clinical study in 60 older healthy adults (55-72 years old). The GoChi group showed a statistically significant increase in the number of lymphocytes and levels of interleukin-2 and immunoglobulin G compared to pre-intervention and the placebo group, whereas the number of CD4, CD8, and natural killer cells or levels of interleukin-4 and immunoglobulin A were not significantly altered. The placebo group showed no significant changes in any immune measures. Whereas the GoChi group showed a significant increase in general feelings of well-being, such as fatigue and sleep, and showed a tendency for increased short-term memory and focus between pre- and post-intervention, the placebo group showed no significant positive changes in these measures. No adverse reactions, abnormal symptoms, or changes in body weight, blood pressure, pulse, visual acuity, urine, stool, or blood biochemistry were seen in either group. In conclusion, daily consumption of GoChi significantly increased several immunological responses and subjective feelings of general well-being without any adverse reactions.

  16. Child Poverty and the Promise of Human Capacity: Childhood as a Foundation for Healthy Aging.

    Science.gov (United States)

    Wise, Paul H

    2016-04-01

    The effect of child poverty and related early life experiences on adult health outcomes and patterns of aging has become a central focus of child health research and advocacy. In this article a critical review of this proliferating literature and its relevance to child health programs and policy are presented. This literature review focused on evidence of the influence of child poverty on the major contributors to adult morbidity and mortality in the United States, the mechanisms by which these associations operate, and the implications for reforming child health programs and policies. Strong and varied evidence base documents the effect of child poverty and related early life experiences and exposures on the major threats to adult health and healthy aging. Studies using a variety of methodologies, including longitudinal and cross-sectional strategies, have reported significant findings regarding cardiovascular disorders, obesity and diabetes, certain cancers, mental health conditions, osteoporosis and fractures, and possibly dementia. These relationships can operate through alterations in fetal and infant development, stress reactivity and inflammation, the development of adverse health behaviors, the conveyance of child chronic illness into adulthood, and inadequate access to effective interventions in childhood. Although the reviewed studies document meaningful relationships between child poverty and adult outcomes, they also reveal that poverty, experiences, and behaviors in adulthood make important contributions to adult health and aging. There is strong evidence that poverty in childhood contributes significantly to adult health. Changes in the content, financing, and advocacy of current child health programs will be required to address the childhood influences on adult health and disease. Policy reforms that reduce child poverty and mitigate its developmental effects must be integrated into broader initiatives and advocacy that also attend to the health and

  17. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects.

    Directory of Open Access Journals (Sweden)

    Jesse F Gregory

    Full Text Available Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5'-phosphate (PLP serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23 were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (<0.5 mg/d to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD to 21.5±4.6 nmol/L (P<0.0001 and increased cystathionine from 131±65 to 199±56 nmol/L (P<0.001. Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by (1H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS. Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P<0.001 and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P<0.05. Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P<0.05, but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.

  18. Effects of submaximal exercise with water ingestion on intraocular pressure in healthy human males

    Directory of Open Access Journals (Sweden)

    Moura M.A.

    2002-01-01

    Full Text Available The effects of exercise and water replacement on intraocular pressure (IOP have not been well established. Furthermore, it is not known whether the temperature of the fluid ingested influences the IOP response. In the present study we determined the effect of water ingestion at three temperatures (10, 24 and 38ºC; 600 ml 15 min before and 240 ml 15, 30 and 45 min after the beginning of each experimental session on the IOP of six healthy male volunteers (age = 24.0 ± 3.5 years, weight = 67.0 ± 4.8 kg, peak oxygen uptake (VO2peak = 47.8 ± 9.1 ml kg-1 min-1. The subjects exercised until exhaustion on a cycle ergometer at a 60% VO2peak in a thermoneutral environment. IOP was measured before and after exercise and during recovery (15, 30 and 45 min using the applanation tonometry method. Skin and rectal temperatures, heart rate and oxygen uptake were measured continuously. IOP was similar for the right eye and the left eye and increased post-water ingestion under both exercising and resting conditions (P<0.05 but did not differ between resting and exercising situations, or between the three water temperatures. Time to exhaustion was not affected by the different water temperatures. Rectal temperature, hydration status, heart rate, oxygen uptake, carbon dioxide extraction and lactate concentration were increased by exercise but were not affected by water temperature. We conclude that IOP was not affected by exercise and that water ingestion increased IOP as expected, regardless of water temperature.

  19. Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.

    Directory of Open Access Journals (Sweden)

    Anja Böhm

    Full Text Available Among obese subjects, metabolically healthy and unhealthy obesity (MHO/MUHO can be differentiated: the latter is characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Aim of this study was, to identify adipocyte-specific metabolic signatures and functional biomarkers for MHO versus MUHO.10 insulin-resistant (IR vs. 10 insulin-sensitive (IS non-diabetic morbidly obese (BMI >40 kg/m2 Caucasians were matched for gender, age, BMI, and percentage of body fat. From subcutaneous fat biopsies, primary preadipocytes were isolated and differentiated to adipocytes in vitro. About 280 metabolites were investigated by a targeted metabolomic approach intracellularly, extracellularly, and in plasma.Among others, aspartate was reduced intracellularly to one third (p = 0.0039 in IR adipocytes, pointing to a relative depletion of citric acid cycle metabolites or reduced aspartate uptake in MUHO. Other amino acids, already known to correlate with diabetes and/or obesity, were identified to differ between MUHO's and MHO's adipocytes, namely glutamine, histidine, and spermidine. Most species of phosphatidylcholines (PCs were lower in MUHO's extracellular milieu, though simultaneously elevated intracellularly, e.g., PC aa C32∶3, pointing to increased PC synthesis and/or reduced PC release. Furthermore, altered arachidonic acid (AA metabolism was found: 15(S-HETE (15-hydroxy-eicosatetraenoic acid; 0 vs. 120pM; p = 0.0014, AA (1.5-fold; p = 0.0055 and docosahexaenoic acid (DHA, C22∶6; 2-fold; p = 0.0033 were higher in MUHO. This emphasizes a direct contribution of adipocytes to local adipose tissue inflammation. Elevated DHA, as an inhibitor of prostaglandin synthesis, might be a hint for counter-regulatory mechanisms in MUHO.We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.

  20. Reliable and versatile immortal muscle cell models from healthy and myotonic dystrophy type 1 primary human myoblasts.

    Science.gov (United States)

    Pantic, Boris; Borgia, Doriana; Giunco, Silvia; Malena, Adriana; Kiyono, Tohru; Salvatori, Sergio; De Rossi, Anita; Giardina, Emiliano; Sangiuolo, Federica; Pegoraro, Elena; Vergani, Lodovica; Botta, Annalisa

    2016-03-01

    Primary human skeletal muscle cells (hSkMCs) are invaluable tools for deciphering the basic molecular mechanisms of muscle-related biological processes and pathological alterations. Nevertheless, their use is quite restricted due to poor availability, short life span and variable purity of the cells during in vitro culture. Here, we evaluate a recently published method of hSkMCs immortalization, relying on ectopic expression of cyclin D1 (CCND1), cyclin-dependent kinase 4 (CDK4) and telomerase (TERT) in myoblasts from healthy donors (n=3) and myotonic dystrophy type 1 (DM1) patients (n=2). The efficacy to maintain the myogenic and non-transformed phenotype, as well as the main pathogenetic hallmarks of DM1, has been assessed. Combined expression of the three genes i) maintained the CD56(NCAM)-positive myoblast population and differentiation potential; ii) preserved the non-transformed phenotype and iii) maintained the CTG repeat length, amount of nuclear foci and aberrant alternative splicing in immortal muscle cells. Moreover, immortal hSkMCs displayed attractive additional features such as structural maturation of sarcomeres, persistence of Pax7-positive cells during differentiation and complete disappearance of nuclear foci following (CAG)7 antisense oligonucleotide (ASO) treatment. Overall, the CCND1, CDK4 and TERT immortalization yields versatile, reliable and extremely useful human muscle cell models to investigate the basic molecular features of human muscle cell biology, to elucidate the molecular pathogenetic mechanisms and to test new therapeutic approaches for DM1 in vitro.

  1. Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples

    Science.gov (United States)

    Derakhshan-Horeh, Marzieh; Abolhassani, Farid; Jafarpour, Farnoosh; Moini, Ashraf; Karbalaie, Khadijeh; Hosseini, Sayyed Morteza; Ostadhosseini, Somayyeh; Nasr-Esfahani, Mohammad Hossein

    2017-01-01

    Background: Imprinted genes are a unique subset of few genes that have been differentially methylated region (DMR) in a parental origin-dependent manner during gametogenesis, and these genes are highly protected during pre-implantation epigenetic reprogramming. Several studies have shown that the particular vulnerability of imprinting genes during suboptimal pre- and peri-conception micro-environments often is occurred by assisted reproduction techniques (ART). This study investigated the methylation status of H19/IGF2 DMR at high-quality expanding/expanded human blastocysts donated by healthy individuals to evaluate the risks linked to ART. Method: Methylation levels of H19/IGF2 DMR were analyzed by bisulfite conversion and sequencing at 18 CpG sites (CpGs) located in this region. Result: The overall percentage of methylated CpGs and the proportion of hyper-methylated clones of H19/IGF2 DMR in analyzed blastocysts were 37.85±4.87% and 43.75±5.1%, respectively. For validation of our technique, the corresponding methylation levels of peripheral human lymphocytes were defined (49.52±1.86% and 50%, respectively). Conclusion: Considering the absence of in vivo- produced human embryos, it is not possible to conclude that the methylation found in H19/IGF2 DMR is actually normal or abnormal. Regarding the possible risks associated with ART, the procedures should be optimized in order to at least reduce some of the epigenetic risks. PMID:27432596

  2. Neuronal correlates of the five factor model (FFM) of human personality: Multimodal imaging in a large healthy sample.

    Science.gov (United States)

    Bjørnebekk, Astrid; Fjell, Anders M; Walhovd, Kristine B; Grydeland, Håkon; Torgersen, Svenn; Westlye, Lars T

    2013-01-15

    Advances in neuroimaging techniques have recently provided glimpse into the neurobiology of complex traits of human personality. Whereas some intriguing findings have connected aspects of personality to variations in brain morphology, the relations are complex and our current understanding is incomplete. Therefore, we aimed to provide a comprehensive investigation of brain-personality relations using a multimodal neuroimaging approach in a large sample comprising 265 healthy individuals. The NEO Personality Inventory was used to provide measures of core aspects of human personality, and imaging phenotypes included measures of total and regional brain volumes, regional cortical thickness and arealization, and diffusion tensor imaging indices of white matter (WM) microstructure. Neuroticism was the trait most clearly linked to brain structure. Higher neuroticism including facets reflecting anxiety, depression and vulnerability to stress was associated with smaller total brain volume, widespread decrease in WM microstructure, and smaller frontotemporal surface area. Higher scores on extraversion were associated with thinner inferior frontal gyrus, and conscientiousness was negatively associated with arealization of the temporoparietal junction. No reliable associations between brain structure and agreeableness and openness, respectively, were found. The results provide novel evidence of the associations between brain structure and variations in human personality, and corroborate previous findings of a consistent neuroanatomical basis of negative emotionality.

  3. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: A review.

    Science.gov (United States)

    Huang, T; Larsen, K T; Ried-Larsen, M; Møller, N C; Andersen, L B

    2014-02-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies.

  4. Effects of ritanserin on the behavioral, neuroendocrine, and cardiovascular responses to meta-chlorophenylpiperazine in healthy human subjects.

    Science.gov (United States)

    Seibyl, J P; Krystal, J H; Price, L H; Woods, S W; D'Amico, C; Heninger, G R; Charney, D S

    1991-09-01

    Ten healthy male subjects were administered i.v. meta-chlorophenylpiperazine (MCPP) (0.1 mg/kg) after oral ritanserin (5-10 mg), a putative 5HT1c/5HT2 (serotonin) antagonist, or placebo. Behavioral responses, cardiovascular effects, and neuroendocrine responses (cortisol, growth hormone, and prolactin) were measured serially for 4 hours after MCPP infusion. Premedication with ritanserin attenuated the MCPP-induced increases in self-rated anxiety and prolactin, and completely antagonized MCPP cortisol elevations. In contrast, ritanserin did not significantly alter growth hormone response to MCPP. These findings suggest a role for 5-HT1c/5-HT2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans.

  5. The development and validation of a digital peak respiratory pressure monitor and its characteristics in healthy human subjects.

    Science.gov (United States)

    Maruthy, K N; Vaz, M

    1999-04-01

    A digital peak respiratory pressure (DPRP) monitor for determining maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was developed using a pressure transducer and an analog to digital converter. It was calibrated using a mercury manometer. Human studies were conducted in healthy young adults in order to determine within-subject and inter-individual variability, as well as diurnal variations and gender differences in maximal respiratory pressures. The calibration studies for the instrument indicated that the instrument recorded accurate pressures, with little temporal drift. Within-subject variability was generally low while inter-individual variability was higher and significant. Gender differences were similar to those recorded in literature for other racial groups. The DPRP monitor described is inexpensive, accurate and portable, making it ideal for use at the patient's bedside.

  6. Initial studies on the variations of load-displacement curves of in vivo human healthy heel pads

    DEFF Research Database (Denmark)

    Matteoli, Sara; Wilhjelm, Jens E.; Virga, Antonio;

    2011-01-01

    The aim of this study was to quantify on the measurement variation of in vivo load-displacement curves by using a group of human healthy heel pads. The recordings were done with a compression device measuring force and displacement. Twenty three heel pads, one from each of 23 subjects aged 20......-35 years, were tested. The load-displacement curves showed the hysteresis, typical for a visco-elastic tissue. Seven load-displacement curves were measured for each subject. Each hysteresis was approximated by a 3rd degree polynomial, which in turn was described by two parameters: the slope and the average...... curvature. No statistically significant tendency (increasing or decreasing) were found for the seven polynomials (chi2 test, P-values of 0.81 and 0.17 for the two parameters, respectively). The study revealed no systematic error in the recorded load-displacement curves. The mean slope and the average...

  7. Investigations on the visco-elastic behaviour of a human healthy heel pad: in vivo compression tests and numerical analysis

    DEFF Research Database (Denmark)

    Matteoli, Sara; Fontanella, Chiara G.; Carniel, Emanuele L.;

    2013-01-01

    The aim of this study was to investigate the viscoelastic behaviour of the human heel pad by comparing the stress–relaxation curves obtained from a compression device used on an in vivo heel pad with those obtained from a threedimensional computer-based subject-specific heel pad model subjected...... to external compression. The three-dimensional model was based on the anatomy revealed by magnetic resonance imaging of a 31-year-old healthy female. The calcaneal fat pad tissue was described with a viscohyperelastic model, while a fibre-reinforced hyperelastic model was formulated for the skin. All......–relaxation and viscous recovery phenomena. The reliability of the investigations was validated by the interpretation of the mechanical response of heel tissues under the application of three pistons with diameter of 15, 20 and 40 mm, at the same displacement rate of about 1.7 mm/s. The maximum and minimum relative...

  8. Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.

    Directory of Open Access Journals (Sweden)

    Patricia Kuzaj

    Full Text Available Mutations in the ABC transporter ABCC6 were recently identified as cause of Pseudoxanthoma elasticum (PXE, a rare genetic disorder characterized by progressive mineralization of elastic fibers. We used an untargeted metabolic approach to identify biochemical differences between human dermal fibroblasts from healthy controls and PXE patients in an attempt to find a link between ABCC6 deficiency, cellular metabolic alterations and disease pathogenesis. 358 compounds were identified by mass spectrometry covering lipids, amino acids, peptides, carbohydrates, nucleotides, vitamins and cofactors, xenobiotics and energy metabolites. We found substantial differences in glycerophospholipid composition, leucine dipeptides, and polypeptides as well as alterations in pantothenate and guanine metabolism to be significantly associated with PXE pathogenesis. These findings can be linked to extracellular matrix remodeling and increased oxidative stress, which reflect characteristic hallmarks of PXE. Our study could facilitate a better understanding of biochemical pathways involved in soft tissue mineralization.

  9. Human methanogen diversity and incidence in healthy and diseased colonic groups using mcrA gene analysis

    Directory of Open Access Journals (Sweden)

    Scanlan Pauline D

    2008-05-01

    Full Text Available Abstract Background The incidence and diversity of human methanogens are insufficiently characterised in the gastrointestinal tract of both health and disease. A PCR and clone library methodology targeting the mcrA gene was adopted to facilitate the two-fold aim of surveying the relative incidence of methanogens in health and disease groups and also to provide an overview of methanogen diversity in the human gastrointestinal tract. Results DNA faecal extracts (207 in total from a group of healthy controls and five gastrointestinal disease groups were investigated. Colorectal cancer, polypectomised, irritable bowel syndrome and the control group had largely equivalent numbers of individuals positive for methanogens (range 45–50%. Methanogen incidence in the inflammatory bowel disease groups was reduced, 24% for ulcerative colitis and 30% for Crohn's disease. Four unique mcrA gene restriction fragment length polymorphism profiles were identified and bioinformatic analyses revealed that the majority of all sequences (94% retrieved from libraries were 100% identical to Methanobrevibacter smithii mcrA gene. In addition, mcrA gene sequences most closely related to Methanobrevibacter oralis and members of the order Methanosarcinales were also recovered. Conclusion The mcrA gene serves as a useful biomarker for methanogen detection in the human gut and the varying trends of methanogen incidence in the human gut could serve as important indicators of intestinal function. Although Methanobrevibacter smithii is the dominant methanogen in both the distal colon of individuals in health and disease, the diversity of methanogens is greater than previously reported. In conclusion, the low incidence of methanogens in Inflammatory Bowel Disease, the functionality of the methanogens and impact of methane production in addition to competitive interactions between methanogens and other microbial groups in the human gastrointestinal tract warrants further

  10. Transfusion of cryopreserved human red blood cells into healthy humans is associated with rapid extravascular hemolysis without a proinflammatory cytokine response.

    Science.gov (United States)

    Hult, Andreas; Malm, Christer; Oldenborg, Per-Arne

    2013-01-01

    Transfusion of stored red blood cells (RBCs) can be associated with adverse side effects. Recent studies in mice transfused with stored RBCs showed that a strong proinflammatory cytokine storm was induced due to extravascular hemolysis already at 2 hours after transfusion. Therefore, we here investigated if transfusion of 2 units of cryopreserved autologous RBCs induced a proinflammatory response in healthy human volunteers. Two units of autologous RBCs, cryopreserved for 16 weeks, were transfused into 10 healthy human volunteers. Serum and blood samples taken at 2 hours before and at 2 and 48 hours after transfusion were analyzed for signs of extravascular hemolysis and the presence of proinflammatory cytokines. At 2 hours after transfusion, transferin-bound serum iron, as well as transferin saturation and total bilirubin, were already significantly increased. These measures all returned back toward that in pretransfusion samples at 48 hours after transfusion. No increases in the production of the proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1β, or tumor necrosis factor-α were detected at any time point after transfusion. Although a significant level of extravascular hemolysis already occurred at 2 hours after transfusion of cryopreserved RBCs, there were no signs of proinflammatory cytokine production up to 48 hours after transfusion. © 2012 American Association of Blood Banks.

  11. Determination of Mirtazapine in Human Plasma by HPLC-MS and Bioavailability of Newly Developed Mirtazapine Tablets in Healthy Volunteers

    Institute of Scientific and Technical Information of China (English)

    LIRong-shan; DINGLi; JIANLong-hai; XIAOHong

    2004-01-01

    Aim To estabhsh a sensitive and specific liquid chromatography-mass spectrometry method for determination of mirtazapine in human plasma and evaluation of its relative bioavailabihty. Methods After being alkalized by 25% ammonia, mirtazapine in the plasma was extracted with n-hexane. Desloratadine was used as internal standard (IS). Solutes were separated on a C18 column with a mobile phase of methanol-ammonium acetate buffer (pH3.5) (75:25). The flow rate of the mobile phase was 1 mL·min-1. Detection was performed on an electrospray ionization (ESI) mass spectrometer and operated in selected ion monitoring (SIM) and positive-ionization mode using target ionsat m/z 266.2 for mirtazapine and m/z 311.2 for the IS. The fragmentor voltage was 90 V. A randomized cross-over study was performed in 20 healthy volunteers. In the two study periods, twenty healthy Chinese male subjects received a single oral dose of mirtazapine 30 mg. Results The calibration curve was linear over the range of 0.3-200 ng·mL-1. The limit of quantitation was 0.1 ng·mL-1. The paramneters for mirtazapine test tablet and reference tablet were as follows.. T1/2 ( 24.7±4.1 ) and (23.6±4.3) h, Tmax (1.6±0.8) and (1.5±0.8) h, Cmax (95.9±29.8) and (91.9±26.7) ng·mL-1, respectively. Conclusion The estabhshed HPLC-MS method is rapid, sensitive and specific for the detemtination of mirtazapine in human plasma. The relative bioavailability was 100.0%±10.8%.

  12. Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects.

    Science.gov (United States)

    Bosson, Jenny; Blomberg, Anders; Pourazar, Jamshid; Mudway, Ian S; Frew, Anthony J; Kelly, Frank J; Sandström, Thomas

    2009-09-01

    Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor kappaB (NFkappaB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-alpha, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFkappaB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

  13. Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease.

    Science.gov (United States)

    Barnes, Virginia M; Kennedy, Adam D; Panagakos, Fotinos; Devizio, William; Trivedi, Harsh M; Jönsson, Thomas; Guo, Lining; Cervi, Shannon; Scannapieco, Frank A

    2014-01-01

    Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine), increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate) and ω-6 fatty acid (linoleate and arachidonate) signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic signatures associated

  14. A third measure-metastable state in the dynamics of spontaneous shape change in healthy human's white cells.

    Directory of Open Access Journals (Sweden)

    Karen A Selz

    2011-04-01

    Full Text Available Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 µm diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, "random" state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t, served as a computable order parameter. Comparison of R(t series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the "random" appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence, sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R

  15. Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

    Science.gov (United States)

    Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

    2012-02-01

    The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

  16. Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease.

    Directory of Open Access Journals (Sweden)

    Virginia M Barnes

    Full Text Available Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine, increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate and ω-6 fatty acid (linoleate and arachidonate signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic

  17. 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.

  18. Pharmacokinetic-pharmacodynamic modelling of opioids in healthy human volunteers. A minireview

    OpenAIRE

    2012-01-01

    Pain is characterized by its multi-dimensional nature, explaining in part why the pharmacokinetic/pharmacodynamic (PK/PD) relationships are not straightforward for analgesics. The first part of this MiniReview gives an overview of PK, PD and PK/PD models, as well as of population approach used in analgesic studies. The second part updates the state-of-the-art in the PK/PD relationship of opioids, focusing on data obtained on experimental human pain models, a useful tool to characterize the PD...

  19. Common multifractality in the heart rate variability and brain activity of healthy humans

    Science.gov (United States)

    Lin, D. C.; Sharif, A.

    2010-06-01

    The influence from the central nervous system on the human multifractal heart rate variability (HRV) is examined under the autonomic nervous system perturbation induced by the head-up-tilt body maneuver. We conducted the multifractal factorization analysis to factor out the common multifractal factor in the joint fluctuation of the beat-to-beat heart rate and electroencephalography data. Evidence of a central link in the multifractal HRV was found, where the transition towards increased (decreased) HRV multifractal complexity is associated with a stronger (weaker) multifractal correlation between the central and autonomic nervous systems.

  20. Hysteresis of haptic vertical and straight ahead in healthy human subjects

    Directory of Open Access Journals (Sweden)

    Tarnutzer Alexander A

    2012-09-01

    Full Text Available Abstract Background The subjective haptic vertical (SHV task requires subjects to adjust the roll orientation of an object, mostly in the roll plane, in such a way that it is parallel to perceived direction of gravity. Previously we found a tendency for clockwise rod rotations to deviate counter-clockwise and vice versa, indicating hysteresis. However, the contributing factors remained unclear. To clarify this we characterized the SHV in terms of handedness, hand used, direction of hand rotation, type of grasping (wrap vs. precision grip and gender, and compared findings with perceived straight-ahead (PSA. Healthy subjects repetitively performed adjustments along SHV (n = 21 and PSA (n = 10 in complete darkness. Results For both SHV and PSA significant effects of the hand used and the direction of rod/plate rotation were found. The latter effect was similar for SHV and PSA, leading to significantly larger counter-clockwise shifts (relative to true earth-vertical and objective straight-ahead for clockwise rotations compared to counter-clockwise rotations irrespective of the handedness and the type of grip. The effect of hand used, however, was opposite in the two tasks: while the SHV showed a counter-clockwise bias when the right hand was used and no bias for the left hand, in the PSA a counter-clockwise bias was obtained for the left hand without a bias for the right hand. No effects of grip and handedness (studied for SHV only on accuracy were observed, however, SHV precision was significantly (p  Conclusions Unimanual haptic tasks require control for the hand used and the type of grip as these factors significantly affect task performance. Furthermore, aligning objects with the SHV and PSA resulted in systematic direction-dependent deviations that could not be attributed to handedness, the hand used, or the type of grip. These deviations are consistent with hysteresis and are likely not related to gravitational pull, as they were

  1. Bioequivalence study of two commercial amoxicillin suspension formulations in healthy human volunteers.

    Science.gov (United States)

    Franco, Gilson C N; Baglie, Sinvaldo; Ruenis, Ana P B; Franco, Luiz M; Cogo, Karina; Oshima-Franco, Yoko; Silva, Paulo; Groppo, Francisco C; Rosalen, Pedro Luiz

    2014-05-01

    To compare the pharmacokinetic profiles and to evaluate the bioequivalence of two commercial amoxicillin suspension formulations (500 mg/5 mL AMOXIL®, reference formulation and AMOXI-PED®, test formulation) in healthy Brazilian volunteers. Under fasting condition, 25 volunteers (13 males and 12 females) were included in this randomized, open-label, two-period crossover (1-week washout interval) bioequivalence study. Blood samples were collected at pre-dose (0 hour) and 0.5, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 12 hours after drug ingestion. Pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0-tlast, and AUC0-∞) were calculated from plasma concentrations for both formulations in each subject. Arithmetic mean values of the pharmacokinetic parameters were: Cmax = 12.004 (± 2.824) μg×mL-1; tmax = 1.118 (± 0.396) h; t1/2 = 1.226 (± 0.179) h; AUC0-tlast = 29.297 (± 6.007) μg×h×mL-1; and AUC0-∞ = 29.299 (± 6.007) μg×h×mL-1 for reference formulation and Cmax = 11.456 (± 2.825) μg×mL-1; tmax = 1.331 (± 0.509) h; t1/2 = 1.141 (± 0.133) h; AUC0-tlast = 28.672 (± 5.778) μg×h×mL-1; and AUC0-∞ = 28.693 (± 5.796) μg×h×mL-1 for test formulation. The confidence intervals (90% CI) for reference and test formulations were, respectively, 90.74 - 100.46% for Cmax and 93.62 - 103.61% for AUC0-t. Based on the results, both formulations of amoxicillin evaluated in this study were considered bioequivalent according to FDA and ANVISA/Brazil criteria.

  2. Robustness of muscle synergies underlying three-dimensional force generation at the hand in healthy humans

    Science.gov (United States)

    Rymer, William Z.; Beer, Randall F.

    2012-01-01

    Previous studies using advanced matrix factorization techniques have shown that the coordination of human voluntary limb movements may be accomplished using combinations of a small number of intermuscular coordination patterns, or muscle synergies. However, the potential use of muscle synergies for isometric force generation has been evaluated mostly using correlational methods. The results of such studies suggest that fixed relationships between the activations of pairs of muscles are relatively rare. There is also emerging evidence that the nervous system uses independent strategies to control movement and force generation, which suggests that one cannot conclude a priori that isometric force generation is accomplished by combining muscle synergies, as shown in movement control. In this study, we used non-negative matrix factorization to evaluate the ability of a few muscle synergies to reconstruct the activation patterns of human arm muscles underlying the generation of three-dimensional (3-D) isometric forces at the hand. Surface electromyographic (EMG) data were recorded from eight key elbow and shoulder muscles during 3-D force target-matching protocols performed across a range of load levels and hand positions. Four synergies were sufficient to explain, on average, 95% of the variance in EMG datasets. Furthermore, we found that muscle synergy composition was conserved across biomechanical task conditions, experimental protocols, and subjects. Our findings are consistent with the view that the nervous system can generate isometric forces by assembling a combination of a small number of muscle synergies, differentially weighted according to task constraints. PMID:22279190

  3. Laser interferometric vibration measurements of the middle ear in healthy humans

    Science.gov (United States)

    Jorge, J. Rodriguez; Hemmert, Werner; Burkhardt, Claus; Zenner, Hans-Peter; Gummer, Anthony W.

    1996-01-01

    The use of spontaneous and evoked otacoustic emissions is now a standard clinical tool for diagnosis of the function of the inner ear. However, it is not possible to extract this information over the entire, functionally relevant frequency range because of imperfect coupling of: (1) stapedial to ear-drum vibrations through the ossicular chain of the middle ear and (2) ear-drum vibrations to air in the external auditory meatus. The problem could be circumvented if it were possible to measure the vibration of the stapes and ear drum. The ear drum can be visualized non-invasively, whereas the stapes is only accessible intra-operatively. Therefore, we designed a laser-interferometric system to non-invasively measure the vibration of the human ear drum. Vibrations were measured with a laser Doppler velocimeter (Polytec OFV-302) coupled into the side arm of an operating microscope (Zeiss OPMI MDM). The wavelength was 633 nm and emitted power was less than 1 mW. Direct coupling through the optics of the operating microscope, instead of through glass fibers, enabled a larger signal-to- noise ratio (20 - 30 dB) due to collection of more reflected light. This coupling scheme avoids the problems associated with having to place a reflecting material on the ear drum. The developed vibration measurement system allows non-invasive, fast and reproducible characterization of the dynamics of the human ear drum and as such can be used for clinical diagnostics.

  4. OMEGA-3 FATTY ACIDS AND LOCAL ANIMAL HUSBANDRY: TASKS AND POSSIBILITIES FOR THE HUMAN HEALTHY NUTRITION

    Directory of Open Access Journals (Sweden)

    J. SEREGI

    2013-12-01

    Full Text Available The positive nutritional effects of PUFA in the human diet nowadays are wellknown. The presence of PUFA in food of animal origin is first of all influenced by the feeding. The animal feeds rich in omega-3 PUFA are considered as basic feeds, such as meadow, grass, hay, green forage, grains etc. In the newly accessed EU countries the traditional breeding methods are typical (housing, lairage, pasture. This tendency is reflected also in the composition of local breeds: the so called indigenous, traditional breeds are characteristic. The development and expansion of local breeding methods is of crucial importance for the viable region, the protection (many times the restoration of environment and for the above mentioned human nutritional advantages. With modern control methods of origin, with adherence of food-safety rules, the local commercialization of the traditional foods can be solved, as many positive examples show in different countries. The need for diverse, tasteful and safe products of special quality is also increasing. Our aim is to support and favour the local, traditional breeding for direct commercialization with ensuring the proper conditions, financial support and legislation.

  5. The lipolytic effect of beta 1- and beta 2-adrenoceptor activation in healthy human volunteers.

    Science.gov (United States)

    Haffner, C A; Kendall, M J; Maxwell, S; Hughes, B

    1993-01-01

    1. We investigated the effect of activation beta 1- and beta 2-adrenoceptors on the process of lipolysis in human volunteers. Ten male subjects underwent a single-blind randomized cross-over trial using infusions of terbutaline (a specific beta 2-adrenoceptor agonist), xamoterol (a partial beta 1-agonist with beta 2-adrenoceptor blocking activity) and saline (placebo control). The effect of these infusions on plasma potassium, glucose, free fatty acids (FFA) (total and individual) and insulin levels was studied. 2. Terbutaline infusion induced a significant rise in plasma glucose and a fall in plasma potassium in keeping with its beta 2-adrenoceptor stimulant properties. Xamoterol infusion had no significant effect on these values. Terbutaline infusion caused a greater rise in total and individual FFA than xamoterol, but both effects were significantly different from placebo. 3. The possible reasons for these results and their implications on the beta-adrenergic control of lipolysis are discussed. PMID:8383517

  6. Atypical evening cortisol profile induces visual recognition memory deficit in healthy human subjects

    Directory of Open Access Journals (Sweden)

    Gilpin Heather

    2008-08-01

    Full Text Available Abstract Background Diurnal rhythm-mediated endogenous cortisol levels in humans are characterised by a peak in secretion after awakening that declines throughout the day to an evening trough. However, a significant proportion of the population exhibits an atypical cycle of diurnal cortisol due to shift work, jet-lag, aging, and mental illness. Results The present study has demonstrated a correlation between elevation of cortisol in the evening and deterioration of visual object recognition memory. However, high evening cortisol levels have no effect on spatial memory. Conclusion This study suggests that atypical evening salivary cortisol levels have an important role in the early deterioration of recognition memory. The loss of recognition memory, which is vital for everyday life, is a major symptom of the amnesic syndrome and early stages of Alzheimer's disease. Therefore, this study will promote a potential physiologic marker of early deterioration of recognition memory and a possible diagnostic strategy for Alzheimer's disease.

  7. The human growth and the healthy environment as a condition of balanced development for the course of human.

    Directory of Open Access Journals (Sweden)

    I. Koukoumpliakos

    2008-01-01

    Full Text Available The rising standard of living has evoked an important burden in the natural environment leading to an immense deterioration of nature. The pollution of the atmosphere and seas, the industrial waste, the climatic changes, the chaotic built-up extension threaten the health of all of us. The responsibility for the pollution of the environment is allocated in everybody. The State is accountable not only for the political planning and the policy that practises, but also for the frame it shapes for the citizens to follow. The improvement of the quality of environment must be combined with the economic progress and growth. The intensity of environmental problems worries the International Community, while the saving and growth of new green forms of energy appear as imperative need. We find already ourselves in a progressive but continuous growth, which has the conditions to develop in the future with spectacular rhythm.The methodology of present work is recommended for: a bibliographic research, mainly Greek, b comparison of the facts that are exported from research, connecting them with the given facts. This comparison leads to the necessary coexistence of a healthy environment and a viable growth.In the results of the research the essential conditions of coexistence are presented between these two. Thus we realise that: a the configuration of an evener environmental conscience is required via the education which would guarantee the balanced and sustainable growth, b the change of perception of people as lords of nature is considered necessary and its replacement by the awareness that the nature does not constitute an inexhaustible resource.With that in mind we conclude that: a the research is required to lead to alternative sources of energy such as the creation of Aeolian parks. It is estimated that more investments in other types of renewable sources of energy such as geothermal and hydroelectric can constitute also advisable solutions. The use of

  8. A First-in-Human Study To Assess the Safety and Pharmacokinetics of Monoclonal Antibodies against Human Cytomegalovirus in Healthy Volunteers.

    Science.gov (United States)

    Dole, Kiran; Segal, Florencia Pereyra; Feire, Adam; Magnusson, Baldur; Rondon, Juan C; Vemula, Janardhana; Yu, Jing; Pang, Yinuo; Pertel, Peter

    2016-05-01

    Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the function of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Here, we evaluated the safety, tolerability, and pharmacokinetics of a single intravenous dose of LJP538 or LJP539 or their combination in healthy volunteers. Adverse events and laboratory abnormalities occurred sporadically with similar incidence between antibody and placebo groups and without any apparent relationship to dose. No subject who received antibody developed a hypersensitivity, infusion-related reaction or anti-drug antibodies. After intravenous administration, both LJP538 and LJP539 demonstrated typical human IgG1 pharmacokinetic properties, with slow clearances, limited volumes of distribution, and long terminal half-lives. The pharmacokinetic parameters were linear and dose proportional for both antibodies across the 50-fold range of doses evaluated in the study. There was no apparent impact on pharmacokinetics when the antibodies were administered alone or in combination. CSJ148 and the individual monoclonal antibodies were safe and well tolerated, with pharmacokinetics as expected for human immunoglobulin.

  9. The Synthesis and Antitumor Activity of Twelve Galloyl Glucosides

    Directory of Open Access Journals (Sweden)

    Chang-Wei Li

    2015-01-01

    Full Text Available Twelve galloyl glucosides 1–12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9, ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11 and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12, are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1, 1,4,6-tri-O-galloyl-β-D-glucopyranose (2, 1,2-di-O-galloyl-β-D-glucopyranose (3, 1,3-di-O-galloyl-β-D-glucopyranose (4, 1,2,3-tri-O-galloyl-α-D-glucopyranose (6 and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10, were synthesized for the first time in the present study. In in vitro MTT assay, 1–12 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50 values were determined to be varied in 17.2–124.7 μM on the tested three human cancer cell lines. In addition, compounds 1–12 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control.

  10. Pharmacokinetic-pharmacodynamic modelling of opioids in healthy human volunteers. a minireview.

    Science.gov (United States)

    Ing Lorenzini, Kuntheavy; Daali, Youssef; Dayer, Pierre; Desmeules, Jules

    2012-03-01

    Pain is characterized by its multi-dimensional nature, explaining in part why the pharmacokinetic/pharmacodynamic (PK/PD) relationships are not straightforward for analgesics. The first part of this MiniReview gives an overview of PK, PD and PK/PD models, as well as of population approach used in analgesic studies. The second part updates the state-of-the-art in the PK/PD relationship of opioids, focusing on data obtained on experimental human pain models, a useful tool to characterize the PD of analgesics. For the so-called weak opioids such as codeine, experimental human studies showed that analgesia relies mainly upon biotransformation into morphine. However, the time-course of plasma concentrations of morphine did not always reflect the time-course of effects, the major site of action being the central nervous system. For tramadol, a correlation has been observed between the analgesic response and the PK of the (+)R-O-demethyl-tramadol metabolite. For 'stronger' opioids such as oxycodone, studies assessing the PK/PD of oxycodone suggested that active metabolite oxymorphone also strongly contributes to the analgesia and that analgesia may also be partially related through an action to peripherally located κ-opioid receptors. Different models have been proposed to describe the time-course of buprenorphine. An effect-compartment model was adopted to describe the PK/PD of morphine and its active metabolite, morphine-6-glucuronide (M6G). A longer blood-effect site equilibration half-life t(1/2) k(e0) was observed for M6G, suggesting a longer onset of action. The studies assessing the PK/PD of fentanyl and its derivatives showed a short t(1/2) k(e0) for analgesia, between 0.2 and 9 min., reflecting a short onset of effect. In conclusion, depending on the speed of transfer between the plasma and the effect site as well as the participation of active metabolites, the time-course of the analgesic effects can be close to the plasma concentrations (alfentanil and

  11. Parathyroid Hormone-Related Protein, Human Adipose-Derived Stem Cells Adipogenic Capacity and Healthy Obesity.

    Science.gov (United States)

    Roca-Rodríguez, María Mar; El Bekay, Rajaa; Garrido-Sanchez, Lourdes; Gómez-Serrano, María; Coin-Aragüez, Leticia; Oliva-Olivera, Wilfredo; Lhamyani, Said; Clemente-Postigo, Mercedes; García-Santos, Eva; de Luna Diaz, Resi; Yubero-Serrano, Elena M; Fernández Real, José M; Peral, Belén; Tinahones, Francisco J

    2015-06-01

    This study aimed to define the potential role of PTHrP on adipogenic regulation and to analyze its relationship with obesity and insulin resistance. This was a cross-sectional study in which visceral (VAT) and subcutaneous (SAT) adipose tissue were extracted from 19 morbidly obese, 10 obese, and 10 lean subjects. PTHrP mRNA levels were measured in VAT and SAT. VAT mesenchymal stem cells and 3T3-L1 cells were differentiated into adipocytes in presence or absence of PTHrP siRNA. PTHrP mRNA and protein levels as well as adipogenic markers were evaluated by Western blotting or qPCR. Immunohistochemistry and immunofluorescence procedures were used for PTHrP intracellular localization. Both human VAT and SAT express PTHrP protein mainly in the nucleolar compartment of stromal vascular fraction cells. The highest levels of PTHrP mRNA and protein expression were detected in undifferentiated mesenchymal cells and progressively decreased during adipogenesis. Remarkably, adipogenic differentiation in human mesenchymal stem cells (A-hMSC) was significantly impaired in a pthrp knockdown. PTHrP seems to be related to obesity-associated insulin resistance (IR), given that we found that PTHrP mRNA expression was higher in VAT from morbidly obese with a low IR degree (MO-L-IR) subjects than those from morbidly obese with a high IR degree (MO-H-IR) and lean subjects, and correlated positively with body mass index and hip circumference. We also found that A-hMSC from MO-L-IRs displayed higher adipogenic capacity than those from both MO-H-IRs and leans. In addition, adipogenesis was impaired in VAT from MO-H-IRs, given that mRNA expression levels of key adipogenic regulators were lower than those from MO-L-IR subjects. PTHrP could be a potential new therapeutic target for the reprograming of adipogenesis and adipose tissue expansion, thus possibly ameliorating the metabolic syndrome in obese subjects.

  12. Acute dark chocolate ingestion is beneficial for hemodynamics via enhancement of erythrocyte deformability in healthy humans.

    Science.gov (United States)

    Radosinska, Jana; Horvathova, Martina; Frimmel, Karel; Muchova, Jana; Vidosovicova, Maria; Vazan, Rastislav; Bernatova, Iveta

    2017-03-01

    Erythrocyte deformability is an important property of erythrocytes that considerably affects blood flow and hemodynamics. The high content of polyphenols present in dark chocolate has been reported to play a protective role in functionality of erythrocytes. We hypothesized that chocolate might influence erythrocytes not only after repeated chronic intake, but also immediately after its ingestion. Thus, we determined the acute effect of dark chocolate and milk (with lower content of biologically active substances) chocolate intake on erythrocyte deformability. We also focused on selected factors that may affect erythrocyte deformability, specifically nitric oxide production in erythrocytes and total antioxidant capacity of plasma. We determined posttreatment changes in the mentioned parameters 2hours after consumption of chocolate compared with their levels before consumption of chocolate. In contrast to milk chocolate intake, the dark chocolate led to a significantly higher increase in erythrocyte deformability. Nitric oxide production in erythrocytes was not changed after dark chocolate intake, but significantly decreased after milk chocolate. The plasma total antioxidant capacity remained unaffected after ingestion of both chocolates. We conclude that our hypothesis was confirmed. Single ingestion of dark chocolate improved erythrocyte deformability despite unchanged nitric oxide production and antioxidant capacity of plasma. Increased deformability of erythrocytes may considerably improve rheological properties of blood and thus hemodynamics in humans, resulting in better tissue oxygenation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Body Site Is a More Determinant Factor than Human Population Diversity in the Healthy Skin Microbiome

    Science.gov (United States)

    Perez Perez, Guillermo I.; Gao, Zhan; Jourdain, Roland; Ramirez, Julia; Gany, Francesca; Clavaud, Cecile; Demaude, Julien

    2016-01-01

    We studied skin microbiota present in three skin sites (forearm, axilla, scalp) in men from six ethnic groups living in New York City. Methods. Samples were obtained at baseline and after four days following use of neutral soap and stopping regular hygiene products, including shampoos and deodorants. DNA was extracted using the MoBio Power Lyzer kit and 16S rRNA gene sequences determined on the IIlumina MiSeq platform, using QIIME for analysis. Results. Our analysis confirmed skin swabbing as a useful method for sampling different areas of the skin because DNA concentrations and number of sequences obtained across subject libraries were similar. We confirmed that skin location was the main factor determining the composition of bacterial communities. Alpha diversity, expressed as number of species observed, was greater in arm than on scalp or axilla in all studied groups. We observed an unexpected increase in α-diversity on arm, with similar tendency on scalp, in the South Asian group after subjects stopped using their regular shampoos and deodorants. Significant differences at phylum and genus levels were observed between subjects of the different ethnic origins at all skin sites. Conclusions. We conclude that ethnicity and particular soap and shampoo practices are secondary factors compared to the ecological zone of the human body in determining cutaneous microbiota composition. PMID:27088867

  14. Evaluation of mineral content in healthy permanent human enamel by Raman spectroscopy

    Science.gov (United States)

    Akkus, Asya; Roperto, Renato; Akkus, Ozan; Porto, Thiago; Teich, Sorin; Lang, Lisa

    2016-01-01

    Background An understanding of tooth enamel mineral content using a clinically viable method is essential since variations in mineralization may serve as an early precursor of a dental health issues, and may predict progression and architecture of decay in addition to assessing the success and effectiveness of the remineralization strategies. Material and Methods Twenty two human incisor teeth were obtained in compliance with the NIH guidelines and site specifically imaged with Raman microscope. The front portion of the teeth was divided into apical, medium and cervical regions and subsequently imaged with Raman microscope in these three locations. Results Measured mineralization levels have varied substantially depending on the regions. It was also observed that, the cervical enamel is the least mineralization as a populational average. Conclusions Enamel mineralization is affected by a many factors such as are poor oral hygiene, alcohol consumption and high intake of dietary carbohydrates, however the net effect manifests as overall mineral content of the enamel. Thus an early identification of the individual with overall low mineral content of the enamel may be a valuable screening tool in determining a group with much higher than average caries risk, allowing intervention before development of caries. Clinically applicable non-invasive techniques that can quantify mineral content, such as Raman analysis, would help answer whether or not mineralization is associated with caries risk. Key words:Enamel, Raman spectroscopy, mineral content, dental caries. PMID:27957268

  15. Body Site Is a More Determinant Factor than Human Population Diversity in the Healthy Skin Microbiome.

    Directory of Open Access Journals (Sweden)

    Guillermo I Perez Perez

    Full Text Available We studied skin microbiota present in three skin sites (forearm, axilla, scalp in men from six ethnic groups living in New York City.Samples were obtained at baseline and after four days following use of neutral soap and stopping regular hygiene products, including shampoos and deodorants. DNA was extracted using the MoBio Power Lyzer kit and 16S rRNA gene sequences determined on the IIlumina MiSeq platform, using QIIME for analysis.Our analysis confirmed skin swabbing as a useful method for sampling different areas of the skin because DNA concentrations and number of sequences obtained across subject libraries were similar. We confirmed that skin location was the main factor determining the composition of bacterial communities. Alpha diversity, expressed as number of species observed, was greater in arm than on scalp or axilla in all studied groups. We observed an unexpected increase in α-diversity on arm, with similar tendency on scalp, in the South Asian group after subjects stopped using their regular shampoos and deodorants. Significant differences at phylum and genus levels were observed between subjects of the different ethnic origins at all skin sites.We conclude that ethnicity and particular soap and shampoo practices are secondary factors compared to the ecological zone of the human body in determining cutaneous microbiota composition.

  16. TLR3 and TLR4 expression in healthy and diseased human endometrium

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    Kimmig Rainer

    2008-09-01

    Full Text Available Abstract Background Toll-like receptors (TLRs play an essential role in the innate immune system by initiating and directing immune response to pathogens. TLRs are expressed in the human endometrium and their regulation might be crucial for the pathogenesis of endometrial diseases. Methods TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3. The expression studies applied quantitative RT-PCR and immunolabelling of both proteins. Results TLR3 and TLR4 proteins were mostly localised to the glandular and luminal epithelium. In addition, TLR4 was present on endometrial dendritic cells, monocytes and macrophages. TLR3 and TLR4 mRNA levels did not show significant changes during the menstrual cycle. In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls. Interestingly, ectopic endometriotic lesions showed a significant increase of TLR3 und TLR4 mRNA expression compared to corresponding eutopic tissues, indicating a local gain of TLR expression. Endometrial hyperplasia and adenocarcinoma revealed significantly reduced receptor levels when compared with postmenopausal controls. The lowest TLR expression levels were determined in poor differentiated carcinoma (grade 3. Conclusion Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.

  17. Metabotropic glutamate2/3 receptor agonism facilitates autonomic recovery after pharmacological panic challenge in healthy humans.

    Science.gov (United States)

    Agorastos, Agorastos; Demiralay, Cüneyt; Stiedl, Oliver; Muhtz, Christoph; Wiedemann, Klaus; Kellner, Michael

    2016-05-01

    Group II metabotropic glutamate receptors (mGluR2/3) are suggested to modulate anxiety, arousal, and stress including autonomic control. However, no study has investigated mGluR2/3-related effects on baseline autonomic activity and reactivity to emotional challenge in humans as yet. Using a double-blind, randomized placebo-controlled, cross-over study design, we investigated the influence of a 1-week treatment with the mGluR2/3 agonist LY544344, prodrug of LY354740, on autonomic reactivity to a cholecystokinin tetrapeptide (CCK-4) panic challenge in eight healthy young men. The main outcome measures were time and frequency domain heart rate variability parameters during baseline, CCK-4 challenge, and recovery. There was no evidence for LY544344-mediated effects on baseline and CCK-4 challenge vagal activity, but a significantly lower recovery low frequency (%) and low frequency/high frequency ratio in the LY544344 group, suggesting enhanced autonomic recovery. This pilot study provides first human data indicating that mGluR2/3 agonism is involved in autonomic responsiveness, suggesting an important role of mGluR2/3 in central autonomic regulation.

  18. High-Caloric and Chocolate Stimuli Processing in Healthy Humans: An Integration of Functional Imaging and Electrophysiological Findings

    Science.gov (United States)

    Asmaro, Deyar; Liotti, Mario

    2014-01-01

    There has been a great deal of interest in understanding how the human brain processes appetitive food cues, and knowing how such cues elicit craving responses is particularly relevant when current eating behavior trends within Westernized societies are considered. One substance that holds a special place with regard to food preference is chocolate, and studies that used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have identified neural regions and electrical signatures that are elicited by chocolate cue presentations. This review will examine fMRI and ERP findings from studies that used high-caloric food and chocolate cues as stimuli, with a focus on responses observed in samples of healthy participants, as opposed to those with eating-related pathology. The utility of using high-caloric and chocolate stimuli as a means of understanding the human reward system will also be highlighted, as these findings may be particularly important for understanding processes related to pathological overeating and addiction to illicit substances. Finally, research from our own lab that focused on chocolate stimulus processing in chocolate cravers and non-cravers will be discussed, as the approach used may help bridge fMRI and ERP findings so that a more complete understanding of appetitive stimulus processing in the temporal and spatial domains may be established. PMID:24434747

  19. High-Caloric and Chocolate Stimuli Processing in Healthy Humans: An Integration of Functional Imaging and Electrophysiological Findings

    Directory of Open Access Journals (Sweden)

    Deyar Asmaro

    2014-01-01

    Full Text Available There has been a great deal of interest in understanding how the human brain processes appetitive food cues, and knowing how such cues elicit craving responses is particularly relevant when current eating behavior trends within Westernized societies are considered. One substance that holds a special place with regard to food preference is chocolate, and studies that used functional magnetic resonance imaging (fMRI and event-related potentials (ERPs have identified neural regions and electrical signatures that are elicited by chocolate cue presentations. This review will examine fMRI and ERP findings from studies that used high-caloric food and chocolate cues as stimuli, with a focus on responses observed in samples of healthy participants, as opposed to those with eating-related pathology. The utility of using high-caloric and chocolate stimuli as a means of understanding the human reward system will also be highlighted, as these findings may be particularly important for understanding processes related to pathological overeating and addiction to illicit substances. Finally, research from our own lab that focused on chocolate stimulus processing in chocolate cravers and non-cravers will be discussed, as the approach used may help bridge fMRI and ERP findings so that a more complete understanding of appetitive stimulus processing in the temporal and spatial domains may be established.

  20. In vivo proton magnetic resonance spectroscopic imaging of the healthy human brain at 9.4 T: initial experience.

    Science.gov (United States)

    Chadzynski, Grzegorz L; Pohmann, Rolf; Shajan, Gunamony; Kolb, Rupert; Bisdas, Sotirios; Klose, Uwe; Scheffler, Klaus

    2015-06-01

    In this study, the feasibility of in vivo proton magnetic resonance spectroscopic imaging ((1)H MRSI) of the healthy human brain at a field strength of 9.4 T, using conventional acquisition techniques, is examined and the initial experience is summarized. MRSI measurements were performed on a 9.4 T MR scanner (Siemens, Erlangen, Germany) equipped with head-only gradient insert (AC84, Siemens) and custom-developed, 8-channel transmit/24-channel receive, and 16-channel transmit/31-channel receive coils. Spectra were acquired from the superior part of the human brain with a modified STEAM sequence. Spectral quantification was done with LCModel software. Reasonable quality and signal-to-noise ratio of the acquired spectra allowed reliable quantification of 12 metabolites (Cramer-Rao lower bounds < 20 %), some of which may be difficult to quantify at field strengths below 7 T due to overlapping resonances or low concentrations. While further developments are necessary to minimize chemical shift displacement and homogeneity of the transmit field, it is demonstrated that in vivo (1)H MRSI at a field strength of 9.4 T is possible. However, further studies applying up-to-date techniques to overcome high-field specific problems are needed in order to assess the potential gain in sensitivity that may be offered by MRSI at 9.4 T.

  1. An increase in the threshold of citric acid-induced cough during chest wall vibration in healthy humans.

    Science.gov (United States)

    Kondo, T; Kobayashi, I; Hayama, N; Ohta, Y

    1998-10-01

    This study tested the hypothesis that the afferent input from the respiratory muscles may be involved in the neural mechanisms inducing cough responses. Coughing was evoked in conscious healthy humans by the inhalation of citric acid aerosol of several concentrations either during or not during chest wall vibration (100 Hz) at the right second intercostal space or during vibration of the right thigh. The mean threshold citric acid concentration to induce coughing was significantly higher during chest wall vibration (geometric mean, 131.8 mg/ml) than without vibration (75.9 mg/ml). Vibration after topical anesthesia of the chest wall skin did not significantly change the threshold concentration of citric acid. The threshold citric acid concentration during vibration of the right thigh did not significantly differ from that without vibration. We concluded that inputs from the chest wall afferent, presumably from the intercostal muscle or costovertebral joint, may have an inhibitory effect on the initiation of coughing at the higher neural structure in conscious humans.

  2. A new process to develop a cocoa powder with higher flavonoid monomer content and enhanced bioavailability in healthy humans.

    Science.gov (United States)

    Tomas-Barberan, Francisco A; Cienfuegos-Jovellanos, Elena; Marín, Alicia; Muguerza, Begoña; Gil-Izquierdo, Angel; Cerda, Begoña; Zafrilla, Pilar; Morillas, Juana; Mulero, Juana; Ibarra, Alvin; Pasamar, María A; Ramón, Daniel; Espín, Juan Carlos

    2007-05-16

    Cocoa is a food rich in polyphenols, mainly the flavonoid procyanidins and flavan-3-ols. The improvement of the cardiovascular function in humans upon cocoa consumption has been specifically linked to the presence of flavan-3-ol derived metabolites in plasma, especially epicatechin glucuronide. In this context, a flavonoid-enriched cocoa-derived product could potentially exert stronger health benefits. The aim of the present study was to obtain a cocoa powder with a higher flavonoid content (mainly enriched in monomer compounds) and assess its flavonoid bioavailability in humans. For this purpose, an unfermented, nonroasted, and blanch-treated cocoa powder (A) was obtained. The powder contained four times more procyanidins than a conventional (B) cocoa powder. Powder A contained eight times more epicatechin and procyanidin B2 than powder B. Cocoa milk drinks were prepared with powder A (MDA) and B (MDB). The bioavailability of flavonoids in both drinks was assessed in a crossover intervention with healthy volunteers. The content of epicatechin glucuronide, the main metabolite detected in plasma, was five-fold higher upon consumption of MDA as compared with MDB. The urinary excretion of metabolites, mainly methyl epicatechin sulfate, was higher upon MDA consumption as compared with MDB, ranging from two- to 12-fold higher depending on the metabolite. These results, together with previous reports regarding the cardiovascular benefits linked to the presence of procyanidin metabolites in plasma, suggest that further clinical trials to validate the health benefits of a flavonoid-enriched cocoa powder are warranted.

  3. Nonlinear population receptive field changes in human area V5/MT+ of healthy subjects with simulated visual field scotomas.

    Science.gov (United States)

    Papanikolaou, Amalia; Keliris, Georgios A; Lee, Sangkyun; Logothetis, Nikos K; Smirnakis, Stelios M

    2015-10-15

    There is extensive controversy over whether the adult visual cortex is able to reorganize following visual field loss (scotoma) as a result of retinal or cortical lesions. Functional magnetic resonance imaging (fMRI) methods provide a useful tool to study the aggregate receptive field properties and assess the capacity of the human visual cortex to reorganize following injury. However, these methods are prone to biases near the boundaries of the scotoma. Retinotopic changes resembling reorganization have been observed in the early visual cortex of normal subjects when the visual stimulus is masked to simulate retinal or cortical scotomas. It is not known how the receptive fields of higher visual areas, like hV5/MT+, are affected by partial stimulus deprivation. We measured population receptive field (pRF) responses in human area V5/MT+ of 5 healthy participants under full stimulation and compared them with responses obtained from the same area while masking the left superior quadrant of the visual field ("artificial scotoma" or AS). We found that pRF estimations in area hV5/MT+ are nonlinearly affected by the AS. Specifically, pRF centers shift towards the AS, while the pRF amplitude increases and the pRF size decreases near the AS border. The observed pRF changes do not reflect reorganization but reveal important properties of normal visual processing under different test-stimulus conditions.

  4. Systemic and mucosal immune responses to sublingual or intramuscular human papilloma virus antigens in healthy female volunteers.

    Directory of Open Access Journals (Sweden)

    Zhiming Huo

    Full Text Available The sublingual route has been proposed as a needle-free option to induce systemic and mucosal immune protection against viral infections. In a translational study of systemic and mucosal humoral immune responses to sublingual or systemically administered viral antigens, eighteen healthy female volunteers aged 19-31 years received three immunizations with a quadravalent Human Papilloma Virus vaccine at 0, 4 and 16 weeks as sublingual drops (SL, n = 12 or intramuscular injection (IM, n = 6. IM antigen delivery induced or boosted HPV-specific serum IgG and pseudovirus-neutralizing antibodies, HPV-specific cervical and vaginal IgG, and elicited circulating IgG and IgA antibody secreting cells. SL antigens induced ~38-fold lower serum and ~2-fold lower cervical/vaginal IgG than IM delivery, and induced or boosted serum virus neutralizing antibody in only 3/12 subjects. Neither route reproducibly induced HPV-specific mucosal IgA. Alternative delivery systems and adjuvants will be required to enhance and evaluate immune responses following sublingual immunization in humans.ClinicalTrials.govNCT00949572.

  5. High-caloric and chocolate stimuli processing in healthy humans: an integration of functional imaging and electrophysiological findings.

    Science.gov (United States)

    Asmaro, Deyar; Liotti, Mario

    2014-01-10

    There has been a great deal of interest in understanding how the human brain processes appetitive food cues, and knowing how such cues elicit craving responses is particularly relevant when current eating behavior trends within Westernized societies are considered. One substance that holds a special place with regard to food preference is chocolate, and studies that used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have identified neural regions and electrical signatures that are elicited by chocolate cue presentations. This review will examine fMRI and ERP findings from studies that used high-caloric food and chocolate cues as stimuli, with a focus on responses observed in samples of healthy participants, as opposed to those with eating-related pathology. The utility of using high-caloric and chocolate stimuli as a means of understanding the human reward system will also be highlighted, as these findings may be particularly important for understanding processes related to pathological overeating and addiction to illicit substances. Finally, research from our own lab that focused on chocolate stimulus processing in chocolate cravers and non-cravers will be discussed, as the approach used may help bridge fMRI and ERP findings so that a more complete understanding of appetitive stimulus processing in the temporal and spatial domains may be established.

  6. Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

    Science.gov (United States)

    Pavlyha, Marianna; Ngai, Colleen; Thomas, Tiffany; Holleran, Stephen; Ramakrishnan, Rajasekhar; Karmally, Wahida; Nandakumar, Renu; Fontanez, Nelson; Obunike, Joseph; Marcovina, Santica M.; Lichtenstein, Alice H.; Matthan, Nirupa R.; Matta, James; Maroccia, Magali; Becue, Frederic; Poitiers, Franck; Swanson, Brian; Cowan, Lisa; Sasiela, William J.; Surks, Howard K.

    2017-01-01

    Background: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism. Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels. The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date. Methods: Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study. They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart. At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined. In 10 participants, postprandial triglycerides and apoB48 levels were measured. Results: Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR. The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL. The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR. Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations. Conclusions: Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL

  7. Prevalence and correlates of oral human papillomavirus infection among healthy males and females in Lima, Peru.

    Science.gov (United States)

    Rosen, Brian J; Walter, Leora; Gilman, Robert H; Cabrerra, Lilia; Gravitt, Patti E; Marks, Morgan A

    2016-03-01

    The incidence of human papillomavirus (HPV) associated head and neck cancers (HNCs) have been increasing in Peru. However, the burden of oral HPV infection in Peru has not been assessed. The objective of this cross-sectional study was to estimate the prevalence and correlates of oral HPV infection in a population-based sample from males and females from Lima, Peru. Between January 2010 and June 2011, a population-based sample of 1099 individuals between the ages of 10 and 85 from a low-income neighbourhood in Lima, Peru was identified through random household sampling. Information on demographic, sexual behaviours, reproductive factors and oral hygiene were collected using interviewer-administered questionnaires. Oral rinse specimens were collected from each participant, and these specimens were genotyped using the Roche Linear Array assay. ORs were used to assess differences in the prevalence of any oral HPV and any high-risk oral HPV infection by demographic factors, sexual practices and oral hygiene among individuals 15+ years of age. The prevalence of any HPV and any high-risk HPV (HR-HPV) was 6.8% and 2.0%, respectively. The three most common types were HPV 55 (3.4%), HPV 6 (1.5%) and HPV 16 (1.1%). Male sex (aOR, 2.21; 95% CI 1.22 to 4.03) was associated with any HPV infection after adjustment. The prevalence of oral HPV in this study was similar to estimates observed in the USA. Higher prevalence of oral infections in males was consistent with a male predominance of HPV-associated HNCs and may signal a sex-specific aetiology in the natural history of infection. 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/

  8. The potential of a high protein-low carbohydrate diet to preserve intrahepatic triglyceride content in healthy humans.

    Directory of Open Access Journals (Sweden)

    Eveline A Martens

    Full Text Available BACKGROUND: Protein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG content induced by acute hypercaloric high-fat and high-fructose diets in humans. OBJECTIVE: To assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC diet compared with an iso-energetic high carbohydrate-low protein (HCLP diet on IHTG content in healthy non-obese subjects, at a constant body weight. DESIGN: Seven men and nine women [mean ± SD age: 24 ± 5 y; BMI: 22.9 ± 2.1 kg/m2] were randomly allocated to a HPLC [30/35/35% of energy (En% from protein/carbohydrate/fat] or a HCLP (5/60/35 En% diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by 1H-magnetic resonance spectroscopy before and after the dietary intervention. RESULTS: IHTG content changed in different directions with the HPLC (CH2H2O: 0.23 ± 0.17 to 0.20 ± 0.10; IHTG%: 0.25 ± 0.20% to 0.22 ± 0.11% compared with the HCLP diet (CH2H2O: 0.34 ± 0.20 vs. 0.38 ± 0.21; IHTG%: 0.38 ± 0.22% vs. 0.43 ± 0.24%, which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055. CONCLUSIONS: A HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight. TRIAL REGISTRATION: Clinicaltrials.gov NCT01551238.

  9. Electromyography of swallowing with fine wire intramuscular electrodes in healthy human: activation sequence of selected hyoid muscles.

    Science.gov (United States)

    Inokuchi, Haruhi; González-Fernández, Marlís; Matsuo, Koichiro; Brodsky, Martin B; Yoda, Mitsumasa; Taniguchi, Hiroshige; Okazaki, Hideto; Hiraoka, Takashi; Palmer, Jeffrey B

    2014-12-01

    Few studies have reported the activation sequence of the swallowing muscles in healthy human participants. We examined temporal characteristics of selected hyoid muscles using fine wire intramuscular electromyography (EMG). Thirteen healthy adults were studied using EMG of the anterior belly of digastric (ABD), geniohyoid (GH), sternohyoid (SH), and masseter (MA, with surface electrodes) while ingesting thin liquid, banana, tofu, and cookie (3 trials each). Onset timing was measured from rectified and integrated EMG. Data were analyzed using repeated-measures ANOVA with Bonferroni correction. When drinking thin liquid, MA, GH, and ABD were activated almost simultaneously, but SH was activated later (using GH onset as 0 s, MA -0.07 (-0.20 to 0.17) second [median (interquartile range)]; ABD 0.00 (-0.10 to 0.07) second; SH 0.17 (0.02 to 0.37) second; P < 0.01). With solid foods, MA contraction preceded GH and ABD; SH was last and delayed relative to liquid swallows (GH 0 s; MA -0.17 (-0.27 to 0.07) second; ABD 0.00 (-0.03 to 0.03) second; SH 0.37 (0.23 to 0.50) second; P < 0.01). The role of the MA differs between solids and liquids so the variation in its timing is expected. The synchronous contraction of GH and ABD was consistent with their role in hyolaryngeal elevation. The SH contracted later with solids, perhaps because if the longer duration of the swallow. The consistent pattern among foods supports the concept of a central pattern generator for pharyngeal swallowing.

  10. Prevalence and Associated Risk Factors of Human Papillomavirus in Healthy Skin Specimens Collected from Rural Anyang, China, 2006-2008.

    Science.gov (United States)

    Deng, Qiuju; Li, Jingjing; Pan, Yaqi; Liu, Fangfang; He, Zhonghu; Liu, Mengfei; Liu, Ying; Zhang, Chanyuan; Abliz, Amir; Shen, Na; Hang, Dong; Xu, Zhongyao; Wang, Qiyan; Ning, Tao; Guo, Chuanhai; Liang, Yongmei; Xu, Ruiping; Zhang, Lixin; Cai, Hong; Ke, Yang

    2016-06-01

    Skin infections with cutaneous human papillomavirus (HPV) have been linked to the development of non-melanoma skin cancer, in which mucosal HPV may also play a crucial role. However, systematic investigations of the distribution and associated factors of HPV infection in healthy skin of the general population are scarce. HPV DNA from palmar exfoliated cells of 2,087 individuals was detected by FAP6085/64 and SPF1/GP6+ primers followed by sequencing. A total of 338 papillomavirus types were detected, with HPV-3, HPV-57, and HPV-49 being the most dominant types. The overall prevalence for HPV DNA on skin was 79.92% and for alpha-, beta-, and gamma-HPV were 27.07%, 38.76%, and 29.56%, respectively. Having multiple lifetime sexual partners (adjusted odds ratio 1.60), being a migrant worker (adjusted odds ratio 2.05, reference: farmers), and frequent bathing (Ptrend = 0.001) were associated with alpha-HPV DNA presence. Advancing age increased the detection risk of beta-HPV (Ptrend = 0.001). Higher education (Ptrend = 0.017) and frequent bathing (Ptrend = 0.001) were positively related to gamma-HPV positivity. This study demonstrates that alpha-HPV commonly exists on healthy skin of the general population in rural China, and alpha- and gamma-HPV infections are related to certain behaviors, different from beta-HPV infection. These findings are crucial to better understanding the biology of HPV infection and may be suggestive of the potential transmission of these viruses.

  11. 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.

  12. Evaluation of Escherichia coli isolates from healthy chickens to determine their potential risk to poultry and human health.

    Science.gov (United States)

    Stromberg, Zachary R; Johnson, James R; Fairbrother, John M; Kilbourne, Jacquelyn; Van Goor, Angelica; Curtiss, Roy; Mellata, Melha

    2017-01-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) strains are important pathogens that cause diverse diseases in humans and poultry. Some E. coli isolates from chicken feces contain ExPEC-associated virulence genes, so appear potentially pathogenic; they conceivably could be transmitted to humans through handling and/or consumption of contaminated meat. However, the actual extraintestinal virulence potential of chicken-source fecal E. coli is poorly understood. Here, we assessed whether fecal E. coli isolates from healthy production chickens could cause diseases in a chicken model of avian colibacillosis and three rodent models of ExPEC-associated human infections. From 304 E. coli isolates from chicken fecal samples, 175 E. coli isolates were screened by PCR for virulence genes associated with human-source ExPEC or avian pathogenic E. coli (APEC), an ExPEC subset that causes extraintestinal infections in poultry. Selected isolates genetically identified as ExPEC and non-ExPEC isolates were assessed in vitro for virulence-associated phenotypes, and in vivo for disease-causing ability in animal models of colibacillosis, sepsis, meningitis, and urinary tract infection. Among the study isolates, 13% (40/304) were identified as ExPEC; the majority of these were classified as APEC and uropathogenic E. coli, but none as neonatal meningitis E. coli. Multiple chicken-source fecal ExPEC isolates resembled avian and human clinical ExPEC isolates in causing one or more ExPEC-associated illnesses in experimental animal infection models. Additionally, some isolates that were classified as non-ExPEC were able to cause ExPEC-associated illnesses in animal models, and thus future studies are needed to elucidate their mechanisms of virulence. These findings show that E. coli isolates from chicken feces contain ExPEC-associated genes, exhibit ExPEC-associated in vitro phenotypes, and can cause ExPEC-associated infections in animal models, and thus may pose a health threat to

  13. Evaluation of Escherichia coli isolates from healthy chickens to determine their potential risk to poultry and human health

    Science.gov (United States)

    Johnson, James R.; Fairbrother, John M.; Kilbourne, Jacquelyn; Van Goor, Angelica; Curtiss, Roy; Mellata, Melha

    2017-01-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) strains are important pathogens that cause diverse diseases in humans and poultry. Some E. coli isolates from chicken feces contain ExPEC-associated virulence genes, so appear potentially pathogenic; they conceivably could be transmitted to humans through handling and/or consumption of contaminated meat. However, the actual extraintestinal virulence potential of chicken-source fecal E. coli is poorly understood. Here, we assessed whether fecal E. coli isolates from healthy production chickens could cause diseases in a chicken model of avian colibacillosis and three rodent models of ExPEC-associated human infections. From 304 E. coli isolates from chicken fecal samples, 175 E. coli isolates were screened by PCR for virulence genes associated with human-source ExPEC or avian pathogenic E. coli (APEC), an ExPEC subset that causes extraintestinal infections in poultry. Selected isolates genetically identified as ExPEC and non-ExPEC isolates were assessed in vitro for virulence-associated phenotypes, and in vivo for disease-causing ability in animal models of colibacillosis, sepsis, meningitis, and urinary tract infection. Among the study isolates, 13% (40/304) were identified as ExPEC; the majority of these were classified as APEC and uropathogenic E. coli, but none as neonatal meningitis E. coli. Multiple chicken-source fecal ExPEC isolates resembled avian and human clinical ExPEC isolates in causing one or more ExPEC-associated illnesses in experimental animal infection models. Additionally, some isolates that were classified as non-ExPEC were able to cause ExPEC-associated illnesses in animal models, and thus future studies are needed to elucidate their mechanisms of virulence. These findings show that E. coli isolates from chicken feces contain ExPEC-associated genes, exhibit ExPEC-associated in vitro phenotypes, and can cause ExPEC-associated infections in animal models, and thus may pose a health threat to

  14. The Influence of Enterococcus faecalis on the Morphology and the Antibody-Binding Capacity of the Intestinal Bacteria of Ten Healthy Human Volunteers

    NARCIS (Netherlands)

    Jansen, G.; Deddens, B.; Wilkinson, M.; Waaij, D. van der

    1995-01-01

    The influence of Enterococcus faecalis on the morphology of the bacterial cells which make up the gut microflora and on the levels of circulating IgG bound to the gut microflora was assessed. After 29 days of pretreatment monitoring, ten healthy human volunteers ingested 10^7 viable cells of E. faec

  15. Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.

    NARCIS (Netherlands)

    Schmeink, C.E.; Bekkers, R.L.M.; Josefsson, A.; Richardus, J.H.; Berndtsson Blom, K.; David, M.P.; Dobbelaere, K.; Descamps, D.

    2011-01-01

    BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n=24

  16. Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.

    NARCIS (Netherlands)

    Schmeink, C.E.; Bekkers, R.L.M.; Josefsson, A.; Richardus, J.H.; Berndtsson Blom, K.; David, M.P.; Dobbelaere, K.; Descamps, D.

    2011-01-01

    BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV

  17. A prospective, double-blind, split-subject study on local skin reactions after administration of human menopausal gonadotrophin preparations to healthy female volunteers

    NARCIS (Netherlands)

    Odink, J.; Zuiderwijk, P.B.M.; Schoen, E.D.; Gan, R.A.

    1995-01-01

    This study was designed to investigate local reactions after the intracutaneous (i.c.) administration of two human menopausal gonadotrophin preparations. For this purpose, 20 healthy female volunteers received six i.c. injections simultaneously, viz. three different batches of both Humegon (Organon,

  18. Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans.

    Science.gov (United States)

    Wijngaarden, Marjolein A; Bakker, Leontine E H; van der Zon, Gerard C; 't Hoen, Peter A C; van Dijk, Ko Willems; Jazet, Ingrid M; Pijl, Hanno; Guigas, Bruno

    2014-11-15

    During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

  19. A randomised, double- blind, cross-over study investigating the prebiotic effect of agave fructans in healthy human subjects.

    Science.gov (United States)

    Ramnani, P; Costabile, A; Bustillo, A G R; Gibson, G R

    2015-01-01

    This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal samples were collected at baseline, on the last day of treatment (days 22 and 58) and washout (days 36 and 72), respectively. Changes in faecal bacterial populations, SCFA and secretory IgA were assessed using fluorescent in situ hybridisation, GC and ELISA, respectively. Bowel movements, stool consistencies, abdominal comfort and mood changes were evaluated by a recorded daily questionnaire. In parallel, the effect of agave fructans on different regions of the colon using a three-stage continuous culture simulator was studied. Predilife significantly increased faecal bifidobacteria (log10 9·6 (sd 0·4)) and lactobacilli (log10 7·7 (sd 0·8)) compared with placebo (log10 9·2 (sd 0·4); P = 0·00) (log10 7·4 (sd 0·7); P = 0·000), respectively. No change was observed for other bacterial groups tested, SCFA, secretory IgA, and PGE2 concentrations between the treatment and placebo. Denaturing gradient gel electrophoresis analysis indicated that bacterial communities were randomly dispersed and no significant differences were observed between Predilife and placebo treatments. The in vitro models showed similar increases in bifidobacterial and lactobacilli populations to that observed with the in vivo trial. To conclude, agave fructans are well tolerated in healthy human subjects and increased bifidobacteria and lactobacilli numbers in vitro and in vivo but did not influence other products of fermentation.

  20. Role of Alveolar β2-Adrenergic Receptors on Lung Fluid Clearance and Exercise Ventilation in Healthy Humans

    Science.gov (United States)

    Paolillo, Stefania; Pellegrino, Riccardo; Salvioni, Elisabetta; Contini, Mauro; Iorio, Annamaria; Bovis, Francesca; Antonelli, Andrea; Torchio, Roberto; Gulotta, Carlo; Locatelli, Alessandro; Agostoni, Piergiuseppe

    2013-01-01

    Background In experimental conditions alveolar fluid clearance is controlled by alveolar β2-adrenergic receptors. We hypothesized that if this occurs in humans, then non-selective β-blockers should reduce the membrane diffusing capacity (DM), an index of lung interstitial fluid homeostasis. Moreover, we wondered whether this effect is potentiated by saline solution infusion, an intervention expected to cause interstitial lung edema. Since fluid retention within the lungs might trigger excessive ventilation during exercise, we also hypothesized that after the β2-blockade ventilation increased in excess to CO2 output and this was further enhanced by interstitial edema. Methods and Results 22 healthy males took part in the study. On day 1, spirometry, lung diffusion for carbon monoxide (DLCO) including its subcomponents DM and capillary volume (VCap), and cardiopulmonary exercise test were performed. On day 2, these tests were repeated after rapid 25 ml/kg saline infusion. Then, in random order 11 subjects were assigned to oral treatment with Carvedilol (CARV) and 11 to Bisoprolol (BISOPR). When heart rate fell at least by 10 beats·min−1, the tests were repeated before (day 3) and after saline infusion (day 4). CARV but not BISOPR, decreased DM (−13±7%, p = 0.001) and increased VCap (+20±22%, p = 0.016) and VE/VCO2 slope (+12±8%, p<0.01). These changes further increased after saline: −18±13% for DM (p<0.01), +44±28% for VCap (p<0.001), and +20±10% for VE/VCO2 slope (p<0.001). Conclusions These findings support the hypothesis that in humans in vivo the β2-alveolar receptors contribute to control alveolar fluid clearance and that interstitial lung fluid may trigger exercise hyperventilation. PMID:23613962

  1. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

    Science.gov (United States)

    Ledgerwood, J E; Coates, E E; Yamshchikov, G; Saunders, J G; Holman, L; Enama, M E; DeZure, A; Lynch, R M; Gordon, I; Plummer, S; Hendel, C S; Pegu, A; Conan-Cibotti, M; Sitar, S; Bailer, R T; Narpala, S; McDermott, A; Louder, M; O'Dell, S; Mohan, S; Pandey, J P; Schwartz, R M; Hu, Z; Koup, R A; Capparelli, E; Mascola, J R; Graham, B S

    2015-12-01

    VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 μg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 μg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

  2. Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans.

    Science.gov (United States)

    Amiot, Marie Josèphe; Knol, Diny; Cardinault, Nicolas; Nowicki, Marion; Bott, Romain; Antona, Claudine; Borel, Patrick; Bernard, Jean-Paul; Duchateau, Guus; Lairon, Denis

    2011-06-01

    Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (-32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (-43%, PE meal vs. control; P < 0.0001) and plasma (-54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans.

  3. Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).

    Science.gov (United States)

    Sandor, B; Papp, J; Mozsik, Gy; Szolcsanyi, J; Keszthelyi, Zs; Juricskay, I; Toth, K; Habon, Tamas

    2014-12-01

    Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

  4. Analysis of the trinucleotide CAG repeat from the human mitochondrial DNA polymerase gene in healthy and diseased individuals.

    Science.gov (United States)

    Rovio, A; Tiranti, V; Bednarz, A L; Suomalainen, A; Spelbrink, J N; Lecrenier, N; Melberg, A; Zeviani, M; Poulton, J; Foury, F; Jacobs, H T

    1999-01-01

    The human nuclear gene (POLG) for the catalytic subunit of mitochondrial DNA polymerase (DNA polymerase gamma) contains a trinucleotide CAG microsatellite repeat within the coding sequence. We have investigated the frequency of different repeat-length alleles in populations of diseased and healthy individuals. The predominant allele of 10 CAG repeats was found at a very similar frequency (approximately 88%) in both Finnish and ethnically mixed population samples, with homozygosity close to the equilibrium prediction. Other alleles of between 5 and 13 repeat units were detected, but no larger, expanded alleles were found. A series of 51 British myotonic dystrophy patients showed no significant variation from controls, indicating an absence of generalised CAG repeat instability. Patients with a variety of molecular lesions in mtDNA, including sporadic, clonal deletions, maternally inherited point mutations, autosomally transmitted mtDNA depletion and autosomal dominant multiple deletions showed no differences in POLG trinucleotide repeat-length distribution from controls. These findings rule out POLG repeat expansion as a common pathogenic mechanism in disorders characterised by mitochondrial genome instability.

  5. Development of a simple radiant heat induced experimental pain model for evaluation of analgesics in normal healthy human volunteers

    Directory of Open Access Journals (Sweden)

    M.U.R Naidu

    2011-01-01

    Full Text Available Objective : Human experimental pain models help to understand the mechanism of the painful conditions and can also be adopted to test analgesic efficacy of drugs. In early phases, the clinical development of new analgesics is hindered due to the lack of reliable tests for the experimental pain models. In the present study, we have developed and validated a simple radiant heat pain model which can be used for future screening of various analgesic agents. Materials and Methods : We have standardized the thermal pain model by recording pain threshold and pain tolerance time in seconds at three different intensities and levels in 24 healthy subjects. Reproducibility of the test procedure was evaluated by recording the pain parameters by two observers on three consecutive days. Validity of model was further tested by evaluating the analgesic effect of tramadol. Results and Conclusions : Use of radiant heat pain model with high intensity and short level was found to produce low variability with coefficient of variation less than 5%. Interobserver and interperiod reproducibility was very good as shown by Bland - Altman plot; with most of the values within ± 2SD. Tramadol produced statistically significant increase in pain threshold time. The newly developed pain model produces a type of experimental pain which is responsive to analgesic effects of tramadol at clinically relevant doses.

  6. Combination of two oxidant stressors suppresses the oxidative stress and enhances the heat shock protein 27 response in healthy humans.

    Science.gov (United States)

    Brerro-Saby, Christelle; Delliaux, Stephane; Steinberg, Jean Guillaume; Boussuges, Alain; Gole, Yoann; Jammes, Yves

    2010-06-01

    We tested the hypothesis that the combination of 2 oxidant stressors (hyperoxia and fatiguing exercise) might reduce or suppress the oxidative stress. We concomitantly measured the plasma concentration of heat shock proteins (Hsp) that protect the cells against the deleterious effects of reactive oxygen species. Healthy humans breathed pure oxygen under normobaric condition for 50-minute periods during which they stayed at rest or executed maximal static handgrip sustained until exhaustion. They also repeated handgrip bouts in normoxic condition. We performed venous blood measurements of 2 markers of the oxidative stress (thiobarbituric acid reactive substances and reduced ascorbic acid) and Hsp27. Under normoxic condition, the handgrip elicited an oxidative stress and a modest increase in plasma Hsp27 level (+7.1 +/- 5.4 ng/mL). Under hyperoxic condition, (1) at rest, compared with the same time schedule in normoxic condition, we measured an oxidative stress (increased thiobarbituric acid reactive substances and decreased reduced ascorbic acid levels) and the plasma Hsp27 level increased (maximal variation, +12.5 +/- 6.0 ng/mL); and (2) after the handgrip, the oxidative stress rapidly disappeared. The combination of both hyperoxia and handgrip bout doubled the Hsp27 response (maximal variation, +24.8 +/- 9.2 ng/mL). Thus, the combination of 2 hits eliciting an oxidative stress seems to induce an adaptive Hsp27 response that might counterbalance an excessive production of reactive oxygen species. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Sourdough fermentation or addition of organic acids or corresponding salts to bread improves nutritional properties of starch in healthy humans.

    Science.gov (United States)

    Liljeberg, H G; Lönner, C H; Björck, I M

    1995-06-01

    Postprandial blood glucose and insulin responses to barley bread containing organic acids or corresponding salts were evaluated in healthy human subjects. The satiety score and the rate and extent of in vitro starch digestion were also studied. Lactic acid was generated by use of a homofermentative starter culture or added to the dough. In addition, products were baked with Ca-lactate, or with Na-propionate at two different concentrations. Consumption of the product baked with a high concentration of Na-propionate significantly lowered the postprandial blood glucose and insulin responses, and significantly prolonged the duration of satiety compared with all other breads. When subjects consumed the breads baked with sourdough, lactic acid and Na-propionate, their glucose and insulin responses were reduced compared with the wholemeal bread alone. The rate of in vitro amylolysis was reduced only by ingestion of the breads containing lactic acid, suggesting that the beneficial impact of Na-propionate on metabolic responses and satiety was related to effects other than a reduced rate of starch hydrolysis. All bread products had a similar concentration of in vitro resistant starch of 1.3-2.1 g/100 g (starch basis). It is concluded that sourdough baking and other fermentation processes may improve the nutritional features of starch. The results also demonstrate that certain salts of organic acids may have metabolic effects.

  8. Reliability of functional and predictive methods to estimate the hip joint centre in human motion analysis in healthy adults.

    Science.gov (United States)

    Kainz, Hans; Hajek, Martin; Modenese, Luca; Saxby, David J; Lloyd, David G; Carty, Christopher P

    2017-03-01

    In human motion analysis predictive or functional methods are used to estimate the location of the hip joint centre (HJC). It has been shown that the Harrington regression equations (HRE) and geometric sphere fit (GSF) method are the most accurate predictive and functional methods, respectively. To date, the comparative reliability of both approaches has not been assessed. The aims of this study were to (1) compare the reliability of the HRE and the GSF methods, (2) analyse the impact of the number of thigh markers used in the GSF method on the reliability, (3) evaluate how alterations to the movements that comprise the functional trials impact HJC estimations using the GSF method, and (4) assess the influence of the initial guess in the GSF method on the HJC estimation. Fourteen healthy adults were tested on two occasions using a three-dimensional motion capturing system. Skin surface marker positions were acquired while participants performed quite stance, perturbed and non-perturbed functional trials, and walking trials. Results showed that the HRE were more reliable in locating the HJC than the GSF method. However, comparison of inter-session hip kinematics during gait did not show any significant difference between the approaches. Different initial guesses in the GSF method did not result in significant differences in the final HJC location. The GSF method was sensitive to the functional trial performance and therefore it is important to standardize the functional trial performance to ensure a repeatable estimate of the HJC when using the GSF method.

  9. Fusarium spp. is able to grow and invade healthy human nails as a single source of nutrients.

    Science.gov (United States)

    Galletti, J; Negri, M; Grassi, F L; Kioshima-Cotica, É S; Svidzinski, T I E

    2015-09-01

    Onychomycosis caused by Fusarium spp. is emerging, but some factors associated with its development remain unclear, such as whether this genus is keratinolytic. The main aim of the present study was to evaluate the ability of Fusarium to use the human nail as a single source of nutrients. We also performed an epidemiological study and antifungal susceptibility testing of Fusarium spp. that were isolated from patients with onychomycosis. The epidemiological study showed that Fusarium species accounted for 12.4 % of onychomycosis cases, and it was the most common among nondermatophyte molds. The most frequent species identified were F. oxysporum (36.5 %), F. solani (31.8 %), and F. subglutinans (8.3 %). Fluconazole was not active against Fusarium spp., and the response to terbinafine varied according to species. Fusarium was able to grow in vitro without the addition of nutrients and invade healthy nails. Thus, we found that Fusarium uses keratin as a single source of nutrients, and the model proposed herein may be useful for future studies on the pathogenesis of onychomycosis.

  10. The twelve dimensional super (2+2)-brane

    CERN Document Server

    Hewson, S F

    1996-01-01

    We discuss supersymmetry in twelve dimensions and present a covariant supersymmetric action for a brane with worldsheet signature (2,2), called a super (2+2)-brane, propagating in the osp(64,12) superspace. This superspace is explicitly constructed, and is trivial in the sense that the spinorial part is a trivial bundle over spacetime, unlike the twisted superspace of usual Poincare supersymmetry. For consistency, it is necessary to take a projection of the superspace. This is the same as the projection required for worldvolume supersymmetry. Upon compactification of this superspace, a torsion is naturally introduced and we produce the membrane and type IIB string actions in 11 and 10 dimensional Minkowski spacetimes. In addition, the compactification of the twelve dimensional supersymmetry algebra produces the correct algebras for these theories, including central charges. These considerations thus give the type IIB string and M-theory a single twelve dimensional origin.

  11. Prevalence of human papillomaviruses in the healthy oral mucosa of women with high-grade squamous intra-epithelial lesion and of their partners as compared to healthy controls.

    Science.gov (United States)

    Tatár, Tímea Zsófia; Kis, Andrea; Szabó, Éva; Czompa, Levente; Boda, Róbert; Tar, Ildikó; Szarka, Krisztina

    2015-10-01

    Oral human papillomavirus (HPV) carriage rates were investigated in relation to genital HPV carriage in women with HPV-associated cervical lesions and male partner of such women, including several couples, in comparison with healthy individuals. Buccal and lingual mucosa of 60 males and 149 females with healthy oral mucosa and without known genital lesion, genital and oral mucosa of further 40 females with cervical high-grade squamous intraepithelial lesion (HSIL) and 34 male sexual partners of women with HSIL (including 20 couples) were sampled. HPV DNA was detected using MY/GP PCR. Genotype was determined by sequencing or restriction fragment length polymorphism. Virus copy numbers were determined by real-time PCR. Overall, oral HPV carriage rate was 5.7% (12/209) in healthy individuals; average copy number was 5.8 × 10(2) copies/1 μg DNA; male and female rates were comparable. Oral carriage in women with HSIL was significantly higher, 20.0% (8/40, P = 0.003); males with partners with HSIL showed a carriage rate of 17.6% (6/34), copy numbers were similar to the healthy controls. In contrast, genital carriage rate (52.9%, 18/34 vs. 82.5%, 33/40; P = 0.006) and average copy number were lower in males (5.0 × 10(5) vs. 7.8 × 10(5) copies/1 μg DNA; P = 0.01). Oral copy numbers in these groups and in healthy individuals were comparable. High-risk genotypes were dominant; couples usually had the same genotype in the genital sample. In conclusion, genital HPV carriage is a risk factor of oral carriage for the individual or for the sexual partner, but alone is not sufficient to produce an oral HPV infection in most cases.

  12. Alcoholics anonymous and other twelve-step programs in recovery.

    Science.gov (United States)

    Detar, D Todd

    2011-03-01

    Recovery is a new way of life for many patients; a life without substances to alter their moods but with a major change improving the physical, psychological, and emotional stability with improved overall health outcomes. The Twelve Steps of the Alcoholics Anonymous (AA) are the foundation of the AA, describing both the necessary actions and the spiritual basis for the recovery program of the AA. The Twelve Steps of the AA provide a structure for which a patient with alcoholism may turn for an answer to their problem of alcohol use, abuse, or dependence. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.

    Science.gov (United States)

    Januszkiewicz, A; Essén, P; McNurlan, M A; Ringdén, O; Garlick, P J; Wernerman, J

    2001-11-01

    In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.

  14. {sup 18}F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing [Affiliated Hospital of Jiangnan University (Wuxi No. 4 People' s Hospital), Department of Nuclear Medicine, Wuxi (China); Pan, Donghui; Xu, Yuping; Yang, Min [Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Wuxi (China); Lang, Lixin; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2015-12-15

    We report the biodistribution and radiation dosimetry of an integrin α{sub v}β{sub 3} specific PET tracer {sup 18}F-AlF-NOTA-E[PEG{sub 4}-c(RGDfk)]{sub 2} (denoted as {sup 18}F-Alfatide II). We also assessed the value of {sup 18}F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of {sup 18}F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with {sup 18}F-FDG (5.55 MBq/kg) and {sup 18}F-Alfatide II. Injection of {sup 18}F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. {sup 18}F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by {sup 18}F-Alfatide II PET, while only ten lesions were visualized by {sup 18}F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that {sup 18}F-Alfatide II is feasible for human studies. {sup 18}F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  15. Characterisation of Population Pharmacokinetics and Endogenous Follicle Stimulating Hormone (FSH) Levels after Multiple Dosing of a Recombinant Human FSH, FE 999049, in Healthy Women

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Roshammer, Daniel; Erichsen, Lars

    2016-01-01

    Objective: The aim of this study was to characterise the population pharmacokinetics of FE 999049, a novel recombinant human follicle-stimulating hormone (FSH), after multiple dosing in healthy women, taking into account endogenous FSH levels and the reproductive hormone dynamics. Methods......: Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling. Results...

  16. Human T-cell responses to Aspergillus fumigatus : In healthy individuals and patients with Aspergillus-related disease

    NARCIS (Netherlands)

    Jolink, H.

    2017-01-01

    The T-cell mediated immune response to Aspergillus fumigatus was studied in healthy individuals and in several patient groups. In peripheral blood of healthy individuals low frequencies of Aspergillus-specific CD4+ T-cells with a Thelper 1 profile were present. In patients with invasive

  17. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Jersie-Christensen, Rosa R; Lyon, David;

    2016-01-01

    BACKGROUND: The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients...... with periodontitis and dental caries to healthy individuals. METHODS: Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically...... and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. CONCLUSIONS: Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease...

  18. 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...

  19. The strong coupling regime of twelve flavors QCD

    NARCIS (Netherlands)

    Silva, Tiago Nunes da; Pallante, Elisabetta

    2012-01-01

    We summarize the results recently reported in Ref.[1] [A. Deuzeman, M.P. Lombardo, T. Nunes da Silva and E. Pallante,"The bulk transition of QCD with twelve flavors and the role of improvement"] for the SU(3) gauge theory with Nf=12 fundamental flavors, and we add some numerical evidence and theoret

  20. EFFORTS Technical annex for the twelve month progress report

    DEFF Research Database (Denmark)

    Andreasen, Jan Lasson; Eriksen, Morten; Thomas christensen, Thomas Vennick;

    The present report is documentation for the work carried out at DTU during the second year of project activity. The report describes the work completed by DTU in general as well as on the active sub-tasks within materials properties, friction modelling and physical modelling, over the last twelve...

  1. Bibliography of Spanish Materials for Students, Grades Seven through Twelve.

    Science.gov (United States)

    California State Dept. of Education, Sacramento.

    This annotated bibliography of Spanish materials for students in grades seven through twelve is divided into the following categories: (1) Art, Drama, Music, and Poetry; (2) Books in Series; (3) Culture; (4) Dictionaries and Encyclopedias; (5) Literature; (6) Mathematics; (7) Physical Education, Health, and Recreation; (8) Reading and Language…

  2. The large-scale functional connectivity correlates of consciousness and arousal during the healthy and pathological human sleep cycle.

    Science.gov (United States)

    Tagliazucchi, Enzo; van Someren, Eus J W

    2017-06-12

    Advances in neuroimaging have greatly improved our understanding of human sleep from a systems neuroscience perspective. However, cognition and awareness are reduced during sleep, hindering the applicability of standard task-based paradigms. Methods recently developed to study spontaneous brain activity fluctuations have proven useful to overcome this limitation. In this review, we focus on the concept of functional connectivity (FC, i.e. statistical covariance between brain activity signals) and its application to functional magnetic resonance imaging (fMRI) data acquired during sleep. We discuss how FC analyses of endogenous brain activity during sleep have contributed towards revealing the large-scale neural networks associated with arousal and conscious awareness. We argue that the neuroimaging of deep sleep can be used to evaluate the predictions of theories of consciousness; at the same time, we highlight some apparent limitations of deep sleep as an experimental model of unconsciousness. In resting state fMRI experiments, the onset of sleep can be regarded as the object of interest but also as an undesirable confound. We discuss a series of articles contributing towards the disambiguation of wakefulness from sleep on the basis of fMRI-derived dynamic FC, and then outline a plan for the development of more general and data-driven sleep classifiers. To complement our review of studies investigating the brain systems of arousal and consciousness during healthy sleep, we then turn to pathological and abnormal sleep patterns. We review the current literature on sleep deprivation studies and sleep disorders, adopting the critical stance that lack of independent vigilance monitoring during fMRI experiments is liable for false positives related to atypical sleep propensity in clinical and sleep-deprived populations. Finally, we discuss multimodal neuroimaging as a promising future direction to achieve a better understanding of the large-scale FC of the brain during

  3. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2016-05-01

    Full Text Available Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl, then a high-salt diet for seven days (18 g/day. The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA. High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL than during the low-salt diet (172.9 ± 8.9 pg/mL. The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01. A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  4. Quantification of DeQi sensation by visual analog scales in healthy humans after immunostimulating acupuncture treatment.

    Science.gov (United States)

    Kou, Wei; Gareus, Isabel; Bell, John D; Goebel, Marion U; Spahn, Günther; Pacheco-López, Gustavo; Bäcker, Marcus; Schedlowski, Manfred; Dobos, Gustav J

    2007-01-01

    Acupuncture is the most popular component of traditional Chinese medicine in Western countries. However, the mechanisms of its effects remain unclear. The therapeutic effect of acupuncture appears when a sensation of DeQi is achieved. We previously reported that repeated, but not single acupuncture treatment affected leukocyte circulation and blood pressure in healthy young humans. The objective of this study was to quantify DeQi sensation by using visual analog scales (VASs) and, to test whether DeQi induction is an important factor for the therapeutic effects of acupuncture in the same cohort. After either acupuncture or sham-acupuncture (placebo) treatment, a questionnaire containing five individual VASs was given to subjects to evaluate their DeQi sensation, including numbness, pressure, heaviness, warmth, and radiating paraesthesia, respectively. A separate VAS to measure their levels of anxiety during the treatment was also included. Our results showed that acupuncture significantly induced higher VAS values for numbness, pressure, warmth, and radiating paraesthesia, but not for heaviness than the placebo across three treatment sessions. Additionally, acupuncture did not induce higher anxiety levels than the placebo. These data confirm that VAS is an objective and reliable way to quantify DeQi sensation and, indicate that DeQi is unique to verum acupuncture treatment. Furthermore, either acupuncture-induced therapeutic effects or DeQi sensation should not be attributed to the stress-mediated effects. In summary, the induction of DeQi in each treatment session is an important factor for the physiological outcomes of repeated acupuncture treatment, and VASs offer objective, an easy and reliable way to assess it.

  5. The effect of topical anal captopril on resting anal pressure in healthy volunteers: the first human pilot study.

    Science.gov (United States)

    Khaikin, M; Bashankaev, B; Sands, D; Weiss, E G; Zbar, A; Wexner, S D

    2014-01-01

    Previous laboratory studies have shown that angiotensin II is produced locally in the rat internal anal sphincter causing potent contraction. The aim of this first human study was to evaluate the safety and manometric effects of topical application of captopril (an ACE inhibitor) on the resting anal pressure in healthy adult volunteers. Ten volunteers, mean age 32.5 years (range, 19-48 years), underwent anorectal manometric evaluation of the mean anal resting pressure (MRAP) and the length of the high-pressure zone (HPZ) before 20 and 60 min after topical application of captopril (0.28 %) cream. Cardiovascular variables (systolic blood pressure, diastolic blood pressure and pulse) were measured before and for up to 1 h after cream application. Side effects were recorded. Adverse events and patient comfort after the cream application were evaluated within a 24-h period by completing a questionnaire. There was no significant change overall in MRAP following captopril administration, although in half the patients, there were reductions in MRAP after treatment. Half the patients had a reduction in the mean resting HPZ length; however, there was no overall difference between pre- and post-treatment values. There was no effect on basic cardiovascular parameters and no correlation between manometric and cardiovascular variables. Topical application of captopril cream may result in a reduction in MRAP in volunteers without anorectal disease. Its use is associated with minimal side effects. It may be a new potential therapeutic option in the treatment of anal fissure. Further studies are required to determine the optimal concentration, dose and frequency of application.

  6. Biodistribution and radiation dosimetry for the tau tracer (18)F-THK-5351 in healthy human subjects.

    Science.gov (United States)

    Hsiao, Ing-Tsung; Lin, Kun-Ju; Huang, Kuo-Lun; Huang, Chin-Chang; Chen, Han-Shiuan; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Okamura, Nobuyuki; Hsu, Jung-Lung

    2017-03-23

    (18)F-THK-5351 is a novel radiotracer that demonstrates high binding selectivity and affinity for tau pathology and exhibits better pharmacokinetics in the living brain than previous THK tau probes. The aim of the present study was to estimate the radiation dose of (18)F-THK-5351 in humans and to compare the clinical radiation dosimetry results to estimations published previously with preclinical data. Methods: Serial whole-body positron emission tomography/computed tomography (PET/CT) imaging was performed for 240 min on 12 healthy volunteers after injecting (18)F-THK-5351 (mean administered activity: 377.8 ± 14.0 MBq, range: 340-397 MBq). The bladder and gallbladder were delineated on PET images, while the other organs were delineated on CT images. Voided urine activity was recorded. The decay-corrected and normalized (18)F-THK-5351 activity of 15 source organ regions as a function of time was entered into the OLINDA/EXM software to calculate the effective dose for each subject following the medical internal radiation dosimetry schema. Results: Overall, the (18)F-THK-5351 injection was well tolerated. The highest mean initial uptakes at 10 min post-injection were measured in the liver (11.4 ± 2.0%), lung (5.7 ± 2.1%), intestine (3.4 ± 0.8%), and kidney (1.4 ± 0.3%). The highest mean absorbed doses of radiation were in the gallbladder wall (242.2 ± 105.2 µGy/MBq), upper large intestine (90.0 ± 15.8 µGy/MBq), small intestine (79.5 ± 13.8 µGy/MBq), and liver (55.8 ± 6.1 µGy/MBq). The resultant whole-body effective dose was 22.7 ± 1.3 µSv/MBq. Conclusion: Our results suggest that a routine injection of 370 MBq of (18)F-THK-5351 would lead to an estimated effective dose of 8.4 mSv; hence, (18)F-THK-5351 shows similar radiation burdens to other commonly used clinical tracers. Our findings in humans were compatible with recently published preclinical dosimetry data extrapolated from mice.

  7. 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- ...

  8. 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 ...

  9. 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 ...

  10. Detection of sul1, sul2 and sul3 in sulphonamide resistant Escherichia coli isolates obtained from healthy humans, pork and pigs in Denmark.

    Science.gov (United States)

    Hammerum, Anette M; Sandvang, Dorthe; Andersen, Sigrid R; Seyfarth, Anne Mette; Porsbo, Lone Jannok; Frimodt-Møller, Niels; Heuer, Ole E

    2006-02-01

    The occurrence of sulphonamide resistance was investigated in 998 Escherichia coli isolates, obtained from pig faeces collected at slaughter, Danish pork collected at retail outlets and from faeces from healthy persons in Denmark. In total 18% (n=35), 20% (n=38) and 26% (n=161) of the E. coli isolates obtained from humans, pork and pigs, respectively, were resistant to sulphonamide. All sulphonamide resistant E. coli isolates were investigated for the presence of sul1, sul2, sul3 and intI1 genes by PCR. The sul1 gene was detected in 40% (n=14), 29% (n=11) and 55% (n=88) of the sulphonamide resistant isolates from humans, pork and pigs, respectively. The sul2 gene was detected in 80% (n=28), 76% (n=29) and 50% (n=81) of isolates from humans, pork and pigs, respectively. None of the human isolates were PCR-positive for sul3, whereas sul3 was present in 5% of the pork isolates and 11% of the pig isolates. Of the 113 sul1 positive isolates, 97 carried the integron-associated integrase gene intI1. All 20 sul3 positive isolates were positive for intI1, and in 12 of these isolates sul3 was the only sulphonamide resistance gene detected. The origin of sul1 and sul2 found in isolates from healthy humans is speculative, but their spread from pigs to humans via the food chain is possible.

  11. Distribution of phylogroups and co-resistance to antimicrobial agents in ampicillin resistant Escherichia coli isolated from healthy humans and from patients with bacteraemia

    DEFF Research Database (Denmark)

    Haugaard, A.; Hammerum, A. M.; Porsbo, Lone Jannok;

    In 2002-03, 31 ampicillin resistant faecal isolates were collected from healthy humans. Moreover, 31 ampicillin resistant blood isolates from patients with bacte-raemia were collected in 2000-02. All isolates were tested positive for the pres-ence of blaTEM. Isolates were characterized by minimum...... inhibitory concentration to antimicrobial agents and examined by PCR to determine their phylogroups. The phylotyping grouped the faecal samples into A (13%), B1 (10%), B2 (42%), D (19%), NT (16%) while the blood isolates grouped into A (16%), B1 (0%), B2 (48%), D (32%) and NT (3%). The frequency...... of resistance in faecal and blood isolates (F/B) was: tetracycline (48%/48%), gentamicin (0%/10%), ciprofloxacin (3%,13%), sulfonamide (68%/77%) and trimethoprim (39%/39%). Conclusion: B2 was the most prevalent phylogroup found both in faecal isolates collected from healthy humans and in blood isolates from...

  12. Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers

    Directory of Open Access Journals (Sweden)

    Elsayed I

    2014-06-01

    Full Text Available Ibrahim Elsayed,1 Aly Ahmed Abdelbary,1 Ahmed Hassen Elshafeey1,21Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, School of Pharmacy, University of Waterloo, ON, CanadaContext: Diacerein (DCN has low aqueous solubility (3.197 mg/L and, consequently, low oral bioavailability (35%–56%. To increase both the solubility and dissolution rate of DCN while maintaining its crystalline nature, high pressure homogenization was used but with only a few homogenization cycles preceded by a simple bottom-up technique.Methods: The nanosuspensions of DCN were prepared using a combined bottom-up/top-down technique. Different surfactants – polyvinyl alcohol, sodium deoxycholate, and sodium dodecyl sulfate – with different concentrations were used for the stabilization of the nanosuspensions. Full factorial experimental design was employed to investigate the influence of formulation variables on nanosuspension characteristics using Design-Expert® Software. Particle size (PS, zeta potential, saturation solubility, in vitro dissolution, and drug crystallinity were studied. Moreover, the in vivo performance of the optimized formula was assessed by bioavailability determination in healthy human volunteers.Results: The concentration of surfactant had a significant effect on both the PS and polydispersity index values. The 1% surfactant concentration showed the lowest PS and polydispersity index values compared with other concentrations. Both type and concentration of surfactant had significant effects on the zeta potential. Formula F8 (containing 1% sodium deoxycholate and Formula F12 (containing 1% sodium dodecyl sulfate had the highest desirability values (0.952 and 0.927, respectively. Hence, they were selected for further characterization. The saturated solubility and mean dissolution time, in the case of F8 and F12, were significantly higher than the coarse drug

  13. Prevalence of and Risk Factors for Anal Human Papillomavirus Infection Among Young Healthy Women in Costa Rica

    Science.gov (United States)

    Castro, Felipe A.; Quint, Wim; Gonzalez, Paula; Katki, Hormuzd A.; Herrero, Rolando; van Doorn, Leen-Jan; Schiffman, Mark; Struijk, Linda; Rodriguez, Ana Cecilia; DelVecchio, Corey; Lowy, Douglas R.; Porras, Carolina; Jimenez, Silvia; Schiller, John; Solomon, Diane; Wacholder, Sholom; Hildesheim, Allan; Kreimer, Aimée R.

    2012-01-01

    Background. Anal cancer is caused by human papillomavirus (HPV), yet little is known about anal HPV infection among healthy young women. Methods. A total of 2017 sexually active women in the control arm of an HPV-16/18 vaccine trial had a single anal specimen collected by a clinician at the 4-year study visit. Samples were tested for HPV by SPF10 PCR/DEIA/LiPA25, version 1. Results. A total of 4% of women had HPV-16, 22% had oncogenic HPV, and 31% had any HPV detected in an anal specimen. The prevalence of anal HPV was higher among women who reported anal intercourse, compared with those who did not (43.4% vs 28.4%; P anal intercourse, cervical HPV (adjusted odds ratio [aOR], 5.3 [95% confidence interval {CI}, 3.4–8.2]), number of sex partners (aOR, 2.2 [95% CI, 1.1–4.6] for ≥4 partners), and number of anal intercourse partners (aOR, 1.9 [95% CI, 1.1–3.3] for ≥2 partners) were independent risk factors for anal HPV detection. Among women who reported no anal intercourse, cervical HPV (aOR, 4.7 [95% CI, 3.7–5.9]), number of sex partners (aOR, 2.4 [95% CI, 1.7–3.4] for ≥4 partners), and report of anal fissures (aOR, 2.3 [95% CI, 1.1–4.8]) were associated with an increased odds of anal HPV detection. Conclusion. Anal HPV is common among young women, even those who report no anal sex, and was associated with cervical HPV infection. Anal fissures in women who report never having had anal intercourse may facilitate HPV exposure. Clinical Trials Registration. NCT00128661. PMID:22850119

  14. Generation of a human induced pluripotent stem cell line from urinary cells of a healthy donor using an integration free vector.

    Science.gov (United States)

    Rossbach, Bella; Hildebrand, Laura; El-Ahmad, Linda; Stachelscheid, Harald; Reinke, Petra; Kurtz, Andreas

    2016-03-01

    We have generated a human induced pluripotent stem cell (iPSC) line derived from urinary cells of a 30 year old healthy female donor. The cells were reprogrammed using a non-integrating viral vector and have shown full differentiation potential. Together with the iPSC-line, the donor provided blood cells for the study of immunological effects of the iPSC line and its derivatives in autologous and allogeneic settings. The line is available and registered in the human pluripotent stem cell registry as BCRTi004-A.

  15. Generation of a human induced pluripotent stem cell line from urinary cells of a healthy donor using integration free Sendai technology.

    Science.gov (United States)

    Rossbach, Bella; Hildebrand, Laura; El-Ahmad, Linda; Stachelscheid, Harald; Reinke, Petra; Kurtz, Andreas

    2016-01-01

    We have generated a human induced pluripotent stem cell (iPSC) line derived from urinary cells of 1 28-30 year old healthy female donor. The cells were reprogrammed using a non-integrating viral vector and shown to have full differentiation potential. Together with the iPSC-lines, the donors provided blood cells for the study of immunological effects of the iPSC line and its derivatives in autologous and allogeneic settings. The line is available and registered in the human pluripotent stem cell registry as BCRTi004-A.

  16. Generation of a human induced pluripotent stem cell line from urinary cells of a healthy donor using an integration free vector

    Directory of Open Access Journals (Sweden)

    Bella Rossbach

    2016-03-01

    Full Text Available We have generated a human induced pluripotent stem cell (iPSC line derived from urinary cells of a 30 year old healthy female donor. The cells were reprogrammed using a non-integrating viral vector and have shown full differentiation potential. Together with the iPSC-line, the donor provided blood cells for the study of immunological effects of the iPSC line and its derivatives in autologous and allogeneic settings. The line is available and registered in the human pluripotent stem cell registry as BCRTi004-A.

  17. Twelve Theses on Reactive Rules for the Web

    OpenAIRE

    Bry, François; Eckert, Michael

    2007-01-01

    Reactivity, the ability to detect and react to events, is an essential functionality in many information systems. In particular, Web systems such as online marketplaces, adaptive (e.g., recommender) sys- tems, and Web services, react to events such as Web page updates or data posted to a server. This article investigates issues of relevance in designing high-level programming languages dedicated to reactivity on the Web. It presents twelve theses on features desira...

  18. The Effect of High Dose Cholecalciferol on Arterial Stiffness and Peripheral and Central Blood Pressure in Healthy Humans

    DEFF Research Database (Denmark)

    Bressendorff, Iain; Brandi, Lisbet; Schou, Morten

    2016-01-01

    and blood pressure in healthy normotensive adults. METHODS: 40 healthy adults were randomised in this double-blinded study to either oral cholecalciferol 3000 IU/day or matching placebo and were followed for 16 weeks to examine any effects on pulse wave velocity (PWV), augmentation index (AIx), peripheral...... and central blood pressure and 24-hour ambulatory blood pressure. RESULTS: 22 subjects in the cholecalciferol arm and 18 subjects in the placebo arm completed the 16 weeks of follow-up. There was no difference in changes in PWV, AIx corrected for heart rate or central or peripheral blood pressure between...... the two groups. There was no correlation between serum 25-hydroxy vitamin D and any of these parameters. CONCLUSIONS: Oral cholecalciferol 3000 IU/day does not affect arterial stiffness or blood pressure after 16 weeks of treatment in healthy normotensive adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT...

  19. A Combination of Constitutive Damage Model and Artificial Neural Networks to Characterize the Mechanical Properties of the Healthy and Atherosclerotic Human Coronary Arteries.

    Science.gov (United States)

    Karimi, Alireza; Rahmati, Seyed Mohammadali; Sera, Toshihiro; Kudo, Susumu; Navidbakhsh, Mahdi

    2017-02-02

    It has been indicated that the content and structure of the elastin and collagen of the arterial wall can subject to a significant alteration due to the atherosclerosis. Consequently, a high tissue stiffness, stress, and even damage/rupture are triggered in the arterial wall. Although many studies so far have been conducted to quantify the mechanical properties of the coronary arteries, none of them consider the role of collagen damage of the healthy and atherosclerotic human coronary arterial walls. Recently, a fiber family-based constitutive equation was proposed to capture the anisotropic mechanical response of the healthy and atherosclerotic human coronary arteries via both the histostructural and uniaxial data. In this study, experimental mechanical measurements along with histological data of the healthy and atherosclerotic arterial walls were employed to determine the constitutive damage parameters and remodeling of the collagen fibers. To do this, the preconditioned arterial tissues were excised from human cadavers within 5-h postmortem, and the mean angle of their collagen fibers was precisely determined. Thereafter, a group of quasistatic axial and circumferential loadings were applied to the arterial walls, and the constrained nonlinear minimization method was employed to identify the arterial parameters according to the axial and circumferential extension data. The remodeling of the collagen fibers during the tensile test was also predicted via Artificial Neural Networks algorithm. Regardless of loading direction, the results presented a noteworthy load-bearing capability and stiffness of the atherosclerotic arteries compared to the healthy ones (P < 0.005). Theoretical fiber angles were found to be consistent with the experimental histological data with less than 2 and 5° difference for the healthy and atherosclerotic arterial walls, respectively. The pseudoelastic damage model data were also compared with that of the experimental data, and

  20. Effect of Homocysteine-Lowering Nutrients on Blood Lipids: Result from Four Randomised, Placebo-Controlled Studies in Healthy Humans

    NARCIS (Netherlands)

    Olthof, M.R.; Vliet, van T.; Verhoef, P.; Zock, P.L.; Katan, M.B.

    2005-01-01

    Background Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals ar

  1. Human Milk Microbial Community Structure Is Relatively Stable and Related to Variations in Macronutrient and Micronutrient Intakes in Healthy Lactating Women.

    Science.gov (United States)

    Williams, Janet E; Carrothers, Janae M; Lackey, Kimberly A; Beatty, Nicola F; York, Mara A; Brooker, Sarah L; Shafii, Bahman; Price, William J; Settles, Matthew L; McGuire, Mark A; McGuire, Michelle K

    2017-09-01

    Background: The human milk microbiome has been somewhat characterized, but little is known about changes over time and relations with maternal factors such as nutrient intake.Objective: We sought to characterize the human milk microbiome and described associations with maternal nutrient intake, time postpartum, delivery mode, and body mass index (BMI; in kg/m(2)).Methods: Milk samples (n = 104) and 24-h diet recalls were collected 9 times from 21 healthy lactating women from day 2 to 6 mo postpartum. Women were classified by BMI as healthy weight (milk microbiome was relatively constant over time, although there were small changes in some of the lesser-abundant genera. Relative abundances of several taxa were associated with BMI, delivery mode, and infant sex. For instance, overweight and obese mothers produced milk with a higher relative abundance of Granulicatella than did healthy-weight women (1.8% ± 0.6% compared with 0.4% ± 0.2%, respectively; P milk microbiome are complex and may include maternal nutrient intake, maternal BMI, delivery mode, and infant sex. Future studies designed to investigate the relation between maternal nutrient intake and the milk microbiome should strive to also evaluate dietary supplement usage and analyze the collected milk for its nutrient content.

  2. Cytotoxic activity against human neuroblastoma and melanoma cells mediated by IgM antibodies derived from peripheral blood of healthy donors.

    Science.gov (United States)

    Devarapu, Satish Kumar; Mamidi, Srinivas; Plöger, Frank; Dill, Othmar; Blixt, Ola; Kirschfink, Michael; Schwartz-Albiez, Reinhard

    2016-06-15

    A small percentage of healthy donors identified in the Western population carry antibodies in their peripheral blood which convey cytotoxic activity against certain human melanoma and neuroblastoma cell lines. We measured the cytotoxic activity of sera and plasmas from healthy donors on the human neuroblastoma cell line Kelly and various melanoma cell lines. Antibodies of IgM isotype, presumably belonging to the class of naturally occurring antibodies, exerted cytotoxic activity in a complement-dependent fashion. Apart from complement-dependent tumor cell lysis, we observed C3 opsonization in all tumor cell lines upon treatment with cytotoxic plasmas. Cell lines tested primarily expressed membrane complement regulatory proteins (mCRP) CD46, CD55 and CD59 to various extents. Blocking of mCRPs by monoclonal antibodies enhanced cell lysis and opsonization, though some melanoma cells remained resistant to complement attack. Epitopes recognized by cytotoxic antibodies were represented by gangliosides such as GD2 and GD3, as evidenced by cellular sialidase pretreatment and enhanced expression of distinct gangliosides. It remains to be clarified why only a small fraction of healthy persons carry these antitumor cytotoxic antibodies.

  3. Heart rate variability, overnight urinary norepinephrine and C-reactive protein: evidence for the cholinergic anti-inflammatory pathway in healthy human adults.

    Science.gov (United States)

    Thayer, J F; Fischer, J E

    2009-04-01

    C-reactive protein (CRP) has been identified as an independent predictor of cardiovascular mortality and morbidity in population-based studies. Recent advances have suggested a prominent role for the autonomic nervous system (ANS) in the regulation of inflammation. However, no in vivo human studies have examined indices of sympathetic and parasympathetic nervous system activity simultaneously in relationship to inflammatory markers in apparently healthy adults. Therefore, the objective of this study was to assess the immunomodulatory effects of the ANS. The study population comprised 611 apparently healthy employees of an airplane manufacturing plant in southern Germany. Urinary NE was positively associated with white blood cell count (WBC) in the total sample. We found an inverse association between indices of vagally mediated heart rate variability and plasma levels of (CRP), which was significantly larger in females than in males after controlling for relevant covariates including NE. Similar results were found using the percentage of interbeat interval differences >50 ms and WBC. We report here for the first time, in a large sample of healthy human adults, evidence supporting the hypothesis of a clinically relevant cholinergic anti-inflammatory pathway after controlling for sympathetic nervous system activity. This suggests an important role for the vagal control of systemic inflammatory activity in cardiovascular disease.

  4. Research on Damage in Trabecular Bone of the Healthy Human Acetabulum at Small Strains Using Nonlinear Micro-finite Element Analysis

    Institute of Scientific and Technical Information of China (English)

    DING Hai; ZHU Zhen-nan; DAI Ke-rong; YE Ming; WANG Cheng-tao

    2008-01-01

    The mechanical properties of the pelvic trabecular bone have been studied at the continuum level. However, nothing is known about the tissue-level damage in the trabecular bone of the healthy human acetabulum at apparent small strains characteristic of habitual. By a DAWING 4000 A supercomputer, nonlinear micro-finite element (μFE) analysis was performed to quantify tissue-level damage accumulation in trabecular bone at small strains. The data indicate that damage in trabecular bone commence at 0.2% apparent strain. The findings imply that tissue yielding can initiate at very low strains in the trabecular bone of the healthy acetabulum and that this local failure has negative consequences on the apparent mechanical properties of trabecular bone.

  5. Healthy People 2020 Tobacco Use Objectives

    Data.gov (United States)

    U.S. Department of Health & Human Services — U.S. Department of Health and Human Services (HHS). Centers for Disease Control and Prevention (CDC). Healthy People 2020 Tobacco Use Objectives. Healthy People...

  6. [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.

  7. 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.

  8. 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.

  9. 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.

  10. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders

    OpenAIRE

    2009-01-01

    Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS ...

  11. The twelve theses: a call to a new reformation

    Directory of Open Access Journals (Sweden)

    John Shelby Spong

    2015-03-01

    Full Text Available With every discovery emerging from the world of science over the last 500 years concerning the origins of the universe and of life itself, the traditional explanations offered by the Christian Church appeared to be more and more dated and irrelevant.  Christian leaders, unable to embrace the knowledge revolution seemed to believe  that the only way to save Christianity was not to disturb the old patterns either by listening to, much less by entertaining the new knowledge. I tried to articulate this challenge in a book entitled: Why Christianity Must Change or Die, published in 1998.  In that book I examined in detail the issues that I was convinced Christianity must address. Shortly after that book was published I reduced its content to twelve theses, which I attached in Luther-like fashion to the great doors on the Chapel of Mansfield College at Oxford University in the United Kingdom. I then mailed copies of those Twelve Theses to every acknowledged Christian leader of the world. It was an attempt to call them into a debate on the real issues that I was certain the Christian Church now faced.  I framed my twelve theses in the boldest, most provocative language possible, designed primarily to elicit response and debate. I welcome responses from Christians everywhere.  I claim no expertise or certainty in developing answers, but I am quite confident that I do understand the problems we are facing as Christians who are seeking to relate to the 21st century.

  12. Pharmacokinetics of flavanone glycosides after ingestion of single doses of fresh-squeezed orange juice versus commercially processed orange juice in healthy humans.

    Science.gov (United States)

    Silveira, Jacqueline Q; Cesar, Thais B; Manthey, John A; Baldwin, Elizabeth A; Bai, Jinhe; Raithore, Smita

    2014-12-31

    Orange juice is a rich source of flavonoids considered beneficial to cardiovascular health in humans. The objective of this study was to analyze the pharmacokinetics of the main flavanone glycosides, hesperidin and narirutin, in humans after the consumption of two styles of orange juice, fresh-squeezed (FOJ) and commercially processed (POJ), differing in their amounts of soluble and insoluble forms of these compounds. Healthy human subjects consumed 11.5 mL/kg body weight of FOJ, and after an interval of 30 days, consumed the same quantity of POJ. The results showed that there were no significant differences in the Tmax of the pharmacokinetic curves for the metabolites of hesperidin and narirutin following the consumption of the two styles of juices, and corrected for differences in doses in the POJ and FOJ, there were also no significant differences in the AUC and Cmax values and percent absorption of these compounds.

  13. Prevalence of high-risk human papillomavirus types 16 and 18 in healthy women with cytologically negative pap smear in Iran.

    Science.gov (United States)

    Safaei, Akbar; Khanlari, Mahsa; Momtahen, Moghdeh; Monabati, Ahmad; Robati, Minoo; Amooei, Sedigheh; Valibeigi, Behnaz; Azarpira, Negar

    2010-01-01

    Because human papillomavirus (HPV) is one of the causal factors in cervical cancer, understanding the epidemiology of this infection is an important step towards developing strategies for prevention. We evaluated the prevalence of high-risk human papillomavirus Types 16 and 18 in cervical samples from 402 healthy women with normal Pap smears by testing with type-specific primers in the polymerase chain reaction. Participants were seen at two gynecological clinics affiliated to the Shiraz University of Medical Sciences in Iran. The prevalence of positive HPV findings was 5.5%; high-risk HPV human papillomavirus Type 16 prevalence was 2% and no patient harbored HPV-18. The prevalence of HPV was 4.5% in younger age group and gradually increased to 20% in the 4 th decade. The prevalence of high-risk HPV was highest in the youngest women and gradually decreased with age. Overall, the prevalence of HPV in our population is low.

  14. Model of the Glucose-Insulin-Glucagon Dynamics after Subcutaneous Administration of a Glucagon Rescue Bolus in Healthy Humans

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Haidar, Ahmad;

    In healthy individuals, insulin and glucagon work in a complex fashion to maintain blood glucose levels within a narrow range. This regulation is distorted in patients with diabetes. The hepatic glucose response due to an elevated glucagon level depends on the current insulin concentration and thus......IU/L). The model can be used for simulation of glucagon bolus strategies for treatment of hypoglycemia and for in silico simulation of dual-hormone artificial pancreas algorithms....

  15. The effect of anodal transcranial direct current stimulation on spatial motor skill learning in healthy and spinal cord injured humans

    OpenAIRE

    Ashworth-Beaumont, Jim

    2012-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. Anodal transcranial direct current stimulation (tDCS) is an intervention which is thought to enhance motor learning in healthy and stroke-injured states, when applied adjunctively during skill learning. We set out to investigate whether anodal tDCS might enhance functional rehabilitation from incomplete tetraplegic SCI. To address current limitations in the measurement of task-dependent skill...

  16. A comparative study on the mechanical properties of the healthy and varicose human saphenous vein under uniaxial loading.

    Science.gov (United States)

    Karimi, Alireza; Navidbakhsh, Mahdi; Kudo, Susumu

    2015-01-01

    Saphenous Vein (SV) due to fatness, age, inactiveness, etc. can be afflicted with varicose. The main reason of the varicose vein is believed to be related to the leg muscle pump which is unable to return the blood to the heart in contradiction of the effect of gravity. As a result of the varicose vein, both the structure and mechanical properties of the vein wall would alter. However, so far there is a lack of knowledge on the mechanical properties of the varicose vein. In this study, a comparative study was carried out to measure the elastic and hyperelastic mechanical properties of the healthy and varicose SVs. Healthy and varicose SVs were removed at autopsy and surgery from seven individuals and then axial tensile load was applied to them up to the failure point. In order to investigate the mechanical behaviour of the vein, this study was benefitted from three different stress definitions, such as 2nd Piola-Kichhoff, engineering and true stresses and four different strain definitions, i.e. Almansi-Hamel, Green-St. Venant, engineering and true strains, to determine the linear mechanical properties of the SVs. A Digital Image Correlation (DIC) technique was used to measure the true strain of the vein walls during load bearing. The non-linear mechanical behaviour of the SVs was also computationally evaluated via the Mooney-Rivlin material model. The true/Cauchy stress-strain diagram exhibited the elastic modulus of the varicose SVs as 45.11% lower than that of the healthy ones. Furthermore, by variation of the stress a significant alteration on the maximum stress of the healthy SVs was observed, but then not for the varicose veins. Additionally, the highest stresses of 4.99 and 0.65 MPa were observed for the healthy and varicose SVs, respectively. These results indicate a weakness in the mechanical strength of the SV when it becomes varicose, owing to the degradation of the elastin and collagen content of the SV. The Mooney-Rivlin hyperelastic and the Finite

  17. Influence of biperiden and bornaprine on sleep in healthy subjects.

    Science.gov (United States)

    Hohagen, F; Lis, S; Riemann, D; Krieger, S; Meyer, C; Montero, R F; Grunze, H; Berger, M

    1994-08-01

    Biperiden, 4 mg, an anticholinergic drug that is relatively selective for the M1 receptor subtype, and bornaprine, 4 mg, a nonselective M1 and M2 antagonist, were administered orally in a randomized, double-blind design to twelve healthy volunteers to investigate the effect on polysomnographically recorded sleep. Both drugs suppressed rapid eye movement (REM) sleep as reflected by an increase of REM latency and a decrease in the percentage of REM sleep period time with the effects of biperiden being more pronounced. No significant effect on slow wave sleep was observed. The results of this study support the hypothesis that both the M1 and the M2 receptor subtype are involved in the regulation of REM sleep in humans.

  18. Identification and Characterization of Eleven Novel Human Gamma-Papillomavirus Isolates from Healthy Skin, Found at Low Frequency in a Normal Population

    OpenAIRE

    Li, Jingjing; Pan, Yaqi; Deng, QiuJu; Cai, Hong; Ke, Yang

    2013-01-01

    Eleven novel human papillomavirus (HPV) types were isolated and characterized from healthy individuals in China. HPV163 belongs to the γ-1 species, HPV 164 and HPV 168 fit in the γ-8 species, HPV 165 and KC5 belongs to the γ-12 species, HPV 168 is closely allied with the γ-4 species, HPV 169 is closely related to the γ-11 species, and HPV 170 is related to the γ-12 species. In addition, HPV 161, HPV 162, and HPV 166 may form a new HPV species of the γ-PV genus. The prevalence of these HPV typ...

  19. Meal-induced changes in splanchnic blood flow and oxygen uptake in middle-aged healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan L; Søndergaard, Susanne B; Møller, Søren

    2006-01-01

    was therefore to measure the splanchnic blood flow and oxygen uptake before and after a standardized meal in a group of middle-aged normal volunteers. MATERIAL AND METHODS: Splanchnic blood flow and oxygen uptake were determined at baseline and after a 3600-kJ mixed meal in 8 healthy women (50-70 years) and 10......). A close association was found between the meal-induced peak increases in splanchnic blood flow and oxygen uptake, but the variables were not related to gender or body surface area of the subjects. CONCLUSIONS: A 3,600-kJ mixed meal induces a significant increase in splanchnic blood flow and oxygen uptake...

  20. 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

  1. 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 ...

  2. 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

  3. Rhizobium promotes non-legumes growth and quality in several production steps: towards a biofertilization of edible raw vegetables healthy for humans.

    Directory of Open Access Journals (Sweden)

    Paula García-Fraile

    Full Text Available The biofertilization of crops with plant-growth-promoting microorganisms is currently considered as a healthy alternative to chemical fertilization. However, only microorganisms safe for humans can be used as biofertilizers, particularly in vegetables that are raw consumed, in order to avoid sanitary problems derived from the presence of pathogenic bacteria in the final products. In the present work we showed that Rhizobium strains colonize the roots of tomato and pepper plants promoting their growth in different production stages increasing yield and quality of seedlings and fruits. Our results confirmed those obtained in cereals and alimentary oil producing plants extending the number of non-legumes susceptible to be biofertilized with rhizobia to those whose fruits are raw consumed. This is a relevant conclusion since safety of rhizobia for human health has been demonstrated after several decades of legume inoculation ensuring that they are optimal bacteria for biofertilization.

  4. 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

  5. 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

  6. [Study on the regular pattern of the distribution of skin epidermal stem cells in the different parts of a healthy human body].

    Science.gov (United States)

    Chen, Xiao-dong; Li, Tian-zeng; Qi, Shao-hai; Xie, Ju-lin; Xu, Ying-bin; Pan, Shu; Yuan, Ji-Shan; Zhang, Tao; Liang, Hui-zhen

    2006-02-01

    To investigate the regular pattern of the distribution of skin epidermal stem cells (ESCs) in the different parts of a healthy human body, and to evaluate the feasibility of the identification of ESCs by P63 and CD29 with single and double labeling. Full-thickness skin samples from 21 parts (including scalp, dorsum of foot, sole of foot, pubic region, and scrotum) of 5 healthy persons were harvested for the study. Immunohistochemistry method with biotin-streptavidin-horseradish peroxidase (SP) was employed with P63 and CD29 as the first antibody to carry out single and double labeling. The staining results were subjected to image analysis. The distribution of the ESCs in the skin from the above parts was observed and expressed as positive unit (PU) value. It was found by P63 single labeling and P63 and CD29 double labeling that the PU value in the dorsum of foot was the lowest while that in the scalp was the highest among all the parts of a healthy body. It was also found by CD29 single labeling that the PU value in the dorsum of foot was the lowest [(11.9 +/- 1.5)%] while highest in the scalp [(29.1 +/- 5.0)%]. The PU value in the hairy region of a human body was evidently higher than that in the non-hairy region (P 0.05). There are more ESCs in the skin from the scalp, mons pubis and scrotum than other parts of the body. Single P63 or CD29 labeling exhibits higher sensitivity but lower specificity in the identification of ESCs. While the double labeling method exhibits higher specificity but lower sensitivity. Above all, it seems that the double labeling may be a simple and effective method for the identification of ESCs.

  7. Twelve tips for teaching medical students with dyslexia.

    Science.gov (United States)

    Shaw, Sebastian Charles Keith; Anderson, John Leeds

    2017-07-01

    Dyslexia is a common learning difficulty. As a result of SS' own experiences as a medical student with dyslexia, we have been researching and teaching on this topic for the past two years. Here, we present twelve tips for teaching medical students with dyslexia. These are gathered from our personal experiences and research, discussions with other educators, and wider literature on the topic. This article aims to shed some light on dyslexia, and also to make practical suggestions. Teaching students with dyslexia should not be a daunting experience. Small changes to existing methods, at minor effort, can make a difference - for example, adding pastel colors to slide backgrounds or avoiding Serif fonts. These tips can help educators gain more insight into dyslexia and incorporate small, beneficial adaptations into their teaching.

  8. Antibacterial activities of extracts from twelve Centaurea species from Turkey

    Directory of Open Access Journals (Sweden)

    Tekeli Yener

    2011-01-01

    Full Text Available Members of the genus Centaurea (Asteraceae have been used in traditional plant-based medicine. The methanol extracts of twelve Centaurea species, of which five are endemic to Turkey flora, were screened for antibacterial activity against four bacteria (Escherichia coli, Bacillus cereus, Salmonella enteritidis, Staphylococcus aureus. The antibacterial activity was evaluated by the microdilution method and the minimum inhibition concentrations (MIC of the extracts were determined. C. cariensis subsp. microlepis exhibited an antimicrobial effect on all tested microorganisms. The extracts from eight Centaurea species (C. balsamita, C. calolepis, C. cariensis subsp. maculiceps, C. cariensis subsp. microlepis, C. kotschyi var. kotschyi, C. solstitialis subsp. solstitialis, C. urvillei subsp. urvillei and C. virgata possessed antibacterial activity against several of the tested microorganisms.

  9. Twelve tips on how to compile a medical educator's portfolio.

    Science.gov (United States)

    Dalton, Claudia Lucy; Wilson, Anthony; Agius, Steven

    2017-09-17

    Medical education is an expanding area of specialist interest for medical professionals. Whilst most doctors will be familiar with the compilation of clinical portfolios for scrutiny of their clinical practice and provision of public accountability, teaching portfolios used specifically to gather and demonstrate medical education activity remain uncommon in many non-academic settings. For aspiring and early career medical educators in particular, their value should not be underestimated. Such a medical educator's portfolio (MEP) is a unique compendium of evidence that is invaluable for appraisal, revalidation, and promotion. It can stimulate and provide direction for professional development, and is a rich source for personal reflection and learning. We recommend that all new and aspiring medical educators prepare an MEP, and suggest twelve tips on how to skillfully compile one.

  10. Spectroscopy of twelve Type Ia supernovae at intermediate redshift

    CERN Document Server

    Balland, C; Pain, R; Walton, N A; Amanullah, R; Astier, Pierre; Ellis, Richard S; Fabbro, S; Goobar, A; Hardin, D; Hook, I M; Irwin, M J; McMahon, R M; Mendez, J M; Ruiz-Lapuente, P; Sainton, G; Schahmaneche, K; Stanishev, V

    2005-01-01

    We present spectra of twelve Type Ia supernovae obtained in 1999 at the William Herschel Telescope and the Nordic Optical Telescope during a search for Type Ia supernovae (SN Ia) at intermediate redshift. The spectra range from z=0.178 to z=0.493, including five high signal-to-noise ratio SN Ia spectra in the still largely unexplored range 0.15 < z < 0.3. Most of the spectra were obtained before or around restframe B-band maximum light. None of them shows the peculiar spectral features found in low-redshift over- or under-luminous SN Ia. Expansion velocities of characteristic spectral absorption features such as SiII at 6355 angs., SII at 5640 angs. and CaII at 3945 angs. are found consistent with their low-z SN Ia counterparts.

  11. Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers--a nutrigenomics perspective.

    Science.gov (United States)

    Persson, Ingrid A L; Persson, Karin; Hägg, Staffan; Andersson, Rolf G G

    2011-01-01

    Evidence suggests that cocoa from the bean of Theobroma cacao L. has beneficial effects on cardiovascular disease. The aim of this study was to investigate if cocoa extract and dark chocolate influence angiotensin-converting enzyme (ACE) and nitric oxide (NO) in human endothelial cells (in vitro) and in healthy volunteers (in vivo). ACE activity was analyzed with a commercial radioenzymatic assay and measured in human endothelial cells from umbilical veins (HUVEC) after 10 minutes of incubation with cocoa extract. NO was measured after 24 hours of incubation. ACE activity and NO were measured at baseline and after 30, 60, and 180 minutes in 16 healthy volunteers after a single intake of 75 g of dark chocolate containing 72% cocoa. Significant inhibition of ACE activity (P < 0.01) and significant increase of NO (P < 0.001) were seen in HUVEC. In the study subjects, a significant inhibition of ACE activity (mean 18%) 3 hours after intake of dark chocolate was seen, but no significant change in NO was seen. According to ACE genotype, significant inhibition of ACE activity was seen after 3 hours in individuals with genotype insertion/insertion and deletion/deletion (mean 21% and 28%, respectively). Data suggest that intake of dark chocolate containing high amount of cocoa inhibits ACE activity in vitro and in vivo.

  12. The large-scale functional connectivity correlates of consciousness and arousal during the healthy and pathological human sleep cycle

    NARCIS (Netherlands)

    Tagliazucchi, E.; van Someren, Eus J W

    2017-01-01

    Advances in neuroimaging have greatly improved our understanding of human sleep from a systems neuroscience perspective. However, cognition and awareness are reduced during sleep, hindering the applicability of standard task-based paradigms. Methods recently developed to study spontaneous brain

  13. Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults.

    Science.gov (United States)

    Szpakowski, Piotr; Biet, Franck; Locht, Camille; Paszkiewicz, Małgorzata; Rudnicka, Wiesława; Druszczyńska, Magdalena; Allain, Fabrice; Fol, Marek; Pestel, Joël; Kowalewicz-Kulbat, Magdalena

    2015-01-01

    Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4(+) T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

  14. Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults

    Directory of Open Access Journals (Sweden)

    Piotr Szpakowski

    2015-01-01

    Full Text Available Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG, the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18 and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+ T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

  15. Continuous theta burst stimulation over the left dorsolateral prefrontal cortex decreases medium load working memory performance in healthy humans.

    Science.gov (United States)

    Schicktanz, Nathalie; Fastenrath, Matthias; Milnik, Annette; Spalek, Klara; Auschra, Bianca; Nyffeler, Thomas; Papassotiropoulos, Andreas; de Quervain, Dominique J-F; Schwegler, Kyrill

    2015-01-01

    The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load.

  16. Prostasin and its regulatory proteins in human placentas from pregnant women with preeclampsia and healthy pregnant controls

    DEFF Research Database (Denmark)

    Frederiksen-Møller, Britta; Jørgensen, Jan Stener; Vogel, Lotte Katrine;

    2015-01-01

    for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension. It was hypothesized...... that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier. METHODS: This hypothesis was addressed in a cross-sectional design with 20 healthy pregnant women and 20 women with new onset of preeclampsia (hypertension and 1......+ for protein on urine dipstick). Blood and urine samples were obtained in relation to delivery and placental biopsies were taken immediately after delivery (control = 39 and preeclampsia 40 weeks). RESULTS: Women with preeclampsia displayed lower levels of aldosterone in plasma (p=0.0475) and in spot urine...

  17. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Rasmussen, S L; Linnet, J

    2004-01-01

    and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were...... measured using scintigraphic and manometric techniques. Isosorbide dinitrate did not change the area under the curve of gastric retention versus time, and did not influence the frequency of antral contractions as assessed at 15-min intervals or the integrated duodenal motility index, as recorded over...... consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal....

  18. Pericardial- Rather than Intramyocardial Fat Is Independently Associated with Left Ventricular Systolic Heart Function in Metabolically Healthy Humans.

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    Full Text Available Obesity is a major risk factor to develop heart failure, in part due to possible lipotoxic effects of increased intramyocardial (MYCL and/or local or paracrine effects of pericardial (PERI lipid accumulation. Recent evidence suggests that MYCL is highly dynamic and might rather be a surrogate marker for disturbed energy metabolism than the underlying cause of cardiac dysfunction. On the other hand, PERI might contribute directly by mechanic and paracrine effects. Therefore, we hypothesized that PERI rather than MYCL is associated with myocardial function.To avoid potential confounding of metabolic disease 31 metabolically healthy subjects (age: 29±10yrs; BMI: 23±3kg/m2 were investigated using 1H-magnetic resonance spectroscopy and imaging. MYCL and PERI, as well as systolic and diastolic left ventricular heart function were assessed. Additionally, anthropometric data and parameters of glucose and lipid metabolism were analyzed. Correlation analysis was performed using Pearson's correlation coefficient. Linear regression model was used to show individual effects of PERI and MYCL on myocardial functional parameters.Correlation analysis with parameters of systolic heart function revealed significant associations for PERI (Stroke Volume (SV: R = -0.513 p = 0.001; CardiacIndex (CI: R = -0.442 p = 0.014, but not for MYCL (SV: R = -0.233; p = 0.207; CI: R = -0.130; p = 0.484. No significant correlations were found for E/A ratio as a parameter of diastolic heart function. In multiple regression analysis CI was negatively predicted by PERI, whereas no impact of MYCL was observed in direct comparison.Cardiac fat depots impact left ventricular heart function in a metabolically healthy population. Direct comparison of different lipid stores revealed that PERI is a more important predictor than MYCL for altered myocardial function.

  19. Human photoreceptor cone density measured with adaptive optics technology (rtx1 device) in healthy eyes: Standardization of measurements.

    Science.gov (United States)

    Zaleska-Żmijewska, Anna; Wawrzyniak, Zbigniew M; Ulińska, Magdalena; Szaflik, Jerzy; Dąbrowska, Anna; Szaflik, Jacek P

    2017-06-01

    The anatomic structures of the anterior segment of the eye enable correct reception of stimuli by the retina, which contains receptors that receive light impulses and transmit them to the visual cortex. The aim of this study was to assess the effect of the size of the sampling window in an adaptive optics (AO) flood-illumination retinal camera (rtx1) on cone density measurements in the eyes of healthy individuals and to investigate the differences in cone density and spacing in different quadrants of the retina. Thirty-three subjects with no ophthalmic or systemic disease underwent a detailed ophthalmologic examination. Photographs of retinal fragments 3 degrees from the fovea were taken using the rtx1 AO retinal camera. We used sampling windows with 3 sizes (50 × 50, 100 × 100, and 250 × 250 μm). Cone density, spacing, and shape were determined using AOdetect software. The median (interquartile range) cone density was 19,269 (4964) cones/mm. There were statistically significant differences between measurements taken with the 50/50 and 250/250-m windows. There were no significant differences in the cone spacing results between any of the windows examined, but the measurements differed according to location between the superior and temporal quadrants. The most common cone shape was hexagonal (47.6%) for all window sizes and locations. These findings may help in the development of a normative database for variation in cone density in healthy subjects and to allow the best window to be chosen for obtain the most correct values for eccentricity measurements of 3 degrees. In our study, the optimal sampling window was 100 × 100 μm.

  20. A Novel Noninvasive Method for Measuring Fatigability of the Quadriceps Muscle in Noncooperating Healthy Subjects

    National Research Council Canada - National Science Library

    Poulsen, Jesper B; Rose, Martin H; Møller, Kirsten; Perner, Anders; Jensen, Bente R

    2015-01-01

    .... On two occasions, separated by seven days, nonvoluntary isometric contractions (twitch and tetanic) of the quadriceps femoris muscle evoked by transcutaneous electrical muscle stimulation were recorded in twelve healthy adults...

  1. 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.

  2. The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

    Science.gov (United States)

    Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

    2007-09-01

    Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

  3. GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.

    Science.gov (United States)

    Besson, Marie; Matthey, Alain; Daali, Youssef; Poncet, Antoine; Vuilleumier, Pascal; Vuillemier, Pascal; Curatolo, Michele; Zeilhofer, Hanns Ulrich; Desmeules, Jules

    2015-03-01

    Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. Clobazam was chosen because of its relatively low sedative properties and CLN because of its use in neuropathic pain. Tolterodine (TLT) was used as an active placebo. The primary outcome parameter was a change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH), which was monitored for 8 hours after drug application. Sedative effects were assessed in parallel to antihyperalgesia. Compared with TLT, recovery from hyperalgesia was significantly faster in the CBZ and CLN groups (P = 0.009). At the time point of maximum effect, the rate of recovery from hyperalgesia was accelerated by CBZ and CLN, relative to placebo by 15.7% (95% confidence interval [CI] 0.8-30.5), P = 0.040, and 28.6% (95% CI 4.5-52.6), P = 0.022, respectively. Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.

  4. Kinetic Modeling of the Tau PET Tracer (18)F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects.

    Science.gov (United States)

    Barret, Olivier; Alagille, David; Sanabria, Sandra; Comley, Robert A; Weimer, Robby M; Borroni, Edilio; Mintun, Mark; Seneca, Nicholas; Papin, Caroline; Morley, Thomas; Marek, Ken; Seibyl, John P; Tamagnan, Gilles D; Jennings, Danna

    2017-07-01

    (18)F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate (18)F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods:(18)F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BPND), and SUVR. BPND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results: AD demonstrated increased (18)F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R(2) > 0.93 was found between BPND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although (18)F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BPND, whereas SUVR sensitivity to regional cerebral blood changes needs further investigation. © 2017 by the Society of Nuclear Medicine and

  5. Aging related changes in mixed basal saliva concentration of sodium, potassium and chloride in healthy non medicated humans.

    Science.gov (United States)

    De Oliveira, Rui; Navas, Eunice; Duran, Carolina; Pinto, Maria; Gutierrez, Jose; Eblen-Zajjur, Antonio

    2014-01-01

    It is well known that the salivary flow is reduced by aging but ionic composition changes associated to aging have been less evaluated. To measure salivary and plasmatic [Na(+)], [K(+)] and [Cl(-)] and to correlate with age in healthy, non-medicated subjects of any gender, 165 healthy participating subjects (over 15 years old) were asked to give sample of 5 mL mix basal saliva in a plastic vial without any stimulation technique, additionally, 5 mL of venous blood was collected. Samples [Na(+)] and [K(+)] were measured by flame photometry (Corning™ M-405) and [Cl(-)] by voltametric chlorometry (Corning™ M-920). Ionic concentrations were expressed as (X±DE; meq.L⁻¹). All three ionic concentrations progressively increased with age, with the lineal regression equation being: [Na(+)] mEq=17.76 + 0.26(Age); r=+0.42; F=31.5; P=0.00001; [K(+)] mEq=13.2+0.15(Age); r=+0.32; F=16.5; P=0.00001; [Cl(-)] mEq=9.05+0.18(Age); r=+0.35; F=7.8; P=0.0071. Age induced changes in salivary ionic concentrations were not associated to blood ionic changes. However, saliva and blood [Na(+)] and [K(+)] were correlated (r=+0.25; F=4.49; P=0.04 and r=+0.30; F=6.98; P=0.01, respectively). Significant association was found among salivary ions: [Na(+)] mEq=9.14+0.99[K(+)] (r=+0.79; F=95.2; P=0.000001); [Cl(-)] mEq=0.95+0.56[Na(+)] (r=0.79; F=106.6; P=0.000001) and [Cl(-)] mEq=3.45+0.69[K(+)] (r=0.73; F=72.5; P=0.000001). These results confirm and measure the impact of aging over the mixed and resting salivary secretion process and suggest that local changes are not related to blood ionic composition.

  6. Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans

    NARCIS (Netherlands)

    Jarvis, S.S.; Gundy, T.B. Van; Galbreath, M.M.; Shibata, S.; Okazaki, K.; Reelick, M.F; Levine, B.D.; Fu, Q.

    2011-01-01

    Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs.

  7. Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

    NARCIS (Netherlands)

    Bigley, A.B.; Rezvani, K.; Shah, N.; Sekine, T.; Balneger, N.; Pistillo, M.; Agha, N.; Kunz, H.; O'Connor, D.P.; Bollard, C.M.; Simpson, R.J.

    2016-01-01

    Cytomegalovirus (CMV) infection markedly expands NKG2C+/NKG2A- NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we

  8. Plasma total ghrelin and leptin levels in human narcolepsy and matched healthy controls: Basal concentrations and response to sodium oxybate

    NARCIS (Netherlands)

    Donjacour, C.E.; Pardi, D.; Aziz, N.A.; Frolich, M.; Roelfsema, F.; Overeem, S.; Pijl, H.; Lammers, G.J.

    2013-01-01

    STUDY OBJECTIVES: Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis. Here, we evaluated whether human hypocretin deficiency, or the narcolepsy therapeutic agent sodium oxy

  9. Angiopoietin-Like Protein 4 is Differentially Regulated by Glucocorticoids and Insulin in vitro and in vivo in Healthy Humans

    NARCIS (Netherlands)

    Raalte, D.H. van; Brands, M.; Serlie, M.J.; Mudde, K.; Stienstra, R.; Sauerwein, H.P.; Kersten, S.; Diamant, M.

    2012-01-01

    Angiopoietin-like protein 4 (Angptl4) is a circulating inhibitor of plasma triglyceride clearance via inhibition of lipoprotein lipase. The aim of the present study was to examine the regulation of Angptl4 by glucocorticoids and insulin in vivo in humans, since these factors regulate Angptl4 express

  10. Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily cinnamon ingestion in healthy humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Blannin, Andrew K

    2009-01-01

    Cinnamon can improve fasting glucose in humans yet data on insulin sensitivity are limited and controversial. Eight male volunteers (aged 25 +/- 1 years, body mass 76.5 +/- 3.0 kg, BMI 24.0 +/- 0.7 kg m(-2); mean +/- SEM) underwent two 14-day interventions involving cinnamon or placebo supplement...

  11. The Effect of Chronic Alprazolam Intake on Memory, Attention, and Psychomotor Performance in Healthy Human Male Volunteers

    Directory of Open Access Journals (Sweden)

    Zahid Sadek Chowdhury

    2016-01-01

    Full Text Available Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL and Delayed Matching to Sample (DMS tests for memory, Rapid Visual Information Processing (RVP for attention, and Choice Reaction Time (CRT for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected.

  12. Continuous Theta Burst Stimulation over the Left Dorsolateral Prefrontal Cortex Decreases Medium Load Working Memory Performance in Healthy Humans

    Science.gov (United States)

    Schicktanz, Nathalie; Fastenrath, Matthias; Milnik, Annette; Spalek, Klara; Auschra, Bianca; Nyffeler, Thomas; Papassotiropoulos, Andreas; de Quervain, Dominique J.-F.; Schwegler, Kyrill

    2015-01-01

    The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load. PMID:25781012

  13. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations

    Directory of Open Access Journals (Sweden)

    Doris M. Jacobs

    2017-08-01

    Full Text Available Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH. We have investigated the effect of theobromine (TB consumption on the concentrations of triglyceride (TG and cholesterol (CH in various lipoprotein (LP subclasses.Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2 with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum.Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses.Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

  14. Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.

    Science.gov (United States)

    Tong, Jenny; Davis, Harold W; Summer, Suzanne; Benoit, Stephen C; Haque, Ahrar; Bidlingmaier, Martin; Tschöp, Matthias H; D'Alessio, David

    2014-07-01

    Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 µg/kg/h), UAG (4 µg/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 men and 8 women) on four occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h intravenous glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (SI), disposition index (DI), and intravenous glucose tolerance (kg) were compared for each subject during the four infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared with the saline control, AG and AG+UAG both decreased AIRg, but UAG alone had no effect. SI did not differ among the treatments. AG, but not UAG, reduced DI and kg and increased plasma growth hormone. UAG did not alter growth hormone, cortisol, glucagon, or free fatty acid levels. UAG selectively decreased glucose and fructose consumption compared with the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or β-cell function and neither augments nor antagonizes the effects of AG.

  15. A Chilean Berry Concentrate Protects against Postprandial Oxidative Stress and Increases Plasma Antioxidant Activity in Healthy Humans

    Science.gov (United States)

    Ávila, Felipe; Echeverria, Guadalupe; Perez, Druso; Trejo, Sebastian; Leighton, Federico

    2017-01-01

    This study formulated and characterized an antioxidant-rich concentrate of berries (BPC-350) produced in Chile, which was used to perform a crossover study aimed at determining the effect of the berries on the modulation of plasma postprandial oxidative stress and antioxidant status. Healthy male volunteers (N = 11) were randomly assigned to three experimental meals: (1) 250 g of ground turkey burger (GTB) + 500 mL of water; (2) 250 g of GTB + 500 mL of 5% BPC-350; (3) 250 g of GTB prepared with 6% BPC-350 + 500 mL of 5% BPC-350. Venous blood samples were collected prior to meal intake and every hour for six hours after intake. Malondialdehyde (MDA), carbonyls in proteins, and DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant capacity were quantified in plasma. Significant differences indicated that BPC-350 decreases MDA plasma concentration and protein carbonyls (p < 0.05). Additionally, a significant increase in the DPPH antioxidant capacity was observed in Meals 2 and 3 when compared to Meal 1 (p < 0.05). The results are discussed in terms of oxidative reactions that occur during digestion at the stomach level and the important effect of oxidative reactions that occur during the thermal processing of red meat. PMID:28243359

  16. A Chilean Berry Concentrate Protects against Postprandial Oxidative Stress and Increases Plasma Antioxidant Activity in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Ines Urquiaga

    2017-01-01

    Full Text Available This study formulated and characterized an antioxidant-rich concentrate of berries (BPC-350 produced in Chile, which was used to perform a crossover study aimed at determining the effect of the berries on the modulation of plasma postprandial oxidative stress and antioxidant status. Healthy male volunteers (N=11 were randomly assigned to three experimental meals: (1 250 g of ground turkey burger (GTB + 500 mL of water; (2 250 g of GTB + 500 mL of 5% BPC-350; (3 250 g of GTB prepared with 6% BPC-350 + 500 mL of 5% BPC-350. Venous blood samples were collected prior to meal intake and every hour for six hours after intake. Malondialdehyde (MDA, carbonyls in proteins, and DPPH (2,2-diphenyl-1-picrylhydrazyl antioxidant capacity were quantified in plasma. Significant differences indicated that BPC-350 decreases MDA plasma concentration and protein carbonyls (p<0.05. Additionally, a significant increase in the DPPH antioxidant capacity was observed in Meals 2 and 3 when compared to Meal 1 (p<0.05. The results are discussed in terms of oxidative reactions that occur during digestion at the stomach level and the important effect of oxidative reactions that occur during the thermal processing of red meat.

  17. Tangerine tomatoes increase total and tetra-cis-lycopene isomer concentrations more than red tomatoes in healthy adult humans.

    Science.gov (United States)

    Burri, Betty Jane Burri; Chapman, Mary H; Neidlinger, Terry R; Seo, Jung S; Ishida, Betty K

    2009-01-01

    Lycopene, or the foods that contain it, may prevent prostate cancer. Studies suggest that some cis-lycopene isomers are more bioavailable than the trans-lycopene isomer. We hypothesized that tangerine tomatoes, which predominantly contain the tetra-cis isomer, should be a good source of bioavailable lycopene. We fed lunches containing 300 g tangerine or red tomato sauce per day to 21 healthy adults in a double-blind crossover design. We collected blood at baseline and after each treatment and washout period. We measured tetra-cis, other cis, and trans lycopene, as well as other carotenoids, by reversed-phase high-performance liquid chromatography. Both tomato sauces increased lycopene concentrations in blood, but the tangerine tomato sauce caused a greater increase of total and tetra-cis-lycopene. The cis isomer(s) may also have facilitated absorption of the trans-lycopene isomer. Indices of oxidative damage decreased as serum lycopene concentrations increased. Our results suggest that total lycopene concentrations can be increased by substituting tetra-cis-lycopene-rich tangerine tomatoes for common red tomatoes in the diet.

  18. Bioequivalence Study of Tramadol + Paracetamol (37.5 + 325 mg In Healthy Human Volunteers in Fasting Condition

    Directory of Open Access Journals (Sweden)

    S. Dhanure

    2013-10-01

    Full Text Available The bioequivalence between test and reference Tramadol and Paracetamol (37.5 + 325 mg tablets was determined in 36 healthy subjects after a single dose in a randomized crossover study under fasting condition. Plasma concentrations were monitored over a period of 24 hour after the drug administration by validated LC/MS/MS analytical method. The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞, AUC0-t / AUC0-∞, Tmax, Kel and t½ were determined from plasma concentration time profile of both formulations and found to be acceptable. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the test and reference products. The analysis of variance did not show any significant difference between the two formulations and 90 % confidence intervals for the ratio of Cmax (92.29 -104.18 %, AUC0-t (99.52 - 104.11 % and AUC0-∞ (99.05 - 104.22 % for tramadol and Cmax (93.56 - 110.27 %, AUC0-t (96.37 - 102.70 % and AUC0-∞ (97.22-103.28 % for paracetamol test and reference products were within the 80 – 125 % interval, satisfying the bioequivalence criteria the US Food and Drug Administration Guidelines. These results indicate that the test and the reference products of Tramadol and Paracetamol are bioequivalent.

  19. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects.

    Science.gov (United States)

    Pungcharoenkul, Kanit; Thongnopnua, Phensri

    2011-11-01

    The impact of consuming curcuminoids containing curcumin at 500 mg/day and 6 g/day for 7 days on plasma antioxidant capacity and serum cholesterol level were determined by using vitamin E 200 IU/day consumption as a comparison. Group A and group B subjects consumed 500 mg and 6 g curcumin, respectively, but group C subjects consumed vitamin E 200 IU. By using the oxygen radical absorbance capacity (ORAC) assay, it was found that plasma antioxidant capacity of group A rose from a baseline of 13% to 24% on day 1 and day 7, as against a 19-20% increase for group B. Serum cholesterol and triglyceride levels were significantly decreased after curcumin treatment at 500 mg/day. By consuming vitamin E, both ORAC values and plasma α-tocopherol concentrations were significantly increased, but only very slight responses on serum cholesterol or triglyceride levels were observed. It is therefore suggested that curcumin supplement would not be appropriate for healthy people except for reducing serum cholesterol or triglyceride levels. The dosage of a daily curcumin supplement at 500 mg is more effective than 6 g, although vitamin E is also considered to be an effective antioxidant supplement.

  20. Continuous theta burst stimulation over the left dorsolateral prefrontal cortex decreases medium load working memory performance in healthy humans.

    Directory of Open Access Journals (Sweden)

    Nathalie Schicktanz

    Full Text Available The dorsolateral prefrontal cortex (DLPFC plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load.

  1. Red wine ingestion prevents microparticle formation after a single high-fat meal--a crossover study in healthy humans.

    Science.gov (United States)

    Bulut, Daniel; Jelich, Uta; Dacanay-Schwarz, Roland; Mügge, Andreas

    2013-06-01

    : The postprandial state after a high-fat meal favors endothelial dysfunction and contributes to the development of atherosclerosis. Little is known about the course of circulating microparticles (MPs) and endothelial progenitor cells (EPCs) after the consumption of a high-fat meal. Both are important for the maintenance and function of endothelial cells. : Ten healthy males consumed a meal with French fries and hot pork sausage. In a crossover design (4 weeks, 1 meal per week) they coingested a drink (mineral water, coke, red wine, liquor). Before and 1 and 2 hours after the meal, blood samples were drawn and endothelial function (expressed as reactive hyperemia index) was measured by a peripheral arterial tone technology. Number of EPCs, total MPs, and endothelial-derived MPs were measured using flow cytometry. : Reactive hyperemia index decreased by about 5% in those tests drinking mineral water, and by about 20% in the coke group, but remained unaffected in the red wine and liquor group. The number of EPCs were not significantly affected. The number of total and endothelial-derived MPs increased after a single meal, most in the coke group (increase by about 62%), and less in the red wine group (by about 5%). : A single high-fat meal deteriorates endothelial function, associated with a significant increase in circulating MPs. These changes were modified by the drink coindigested to the meal. The postprandial state was getting worse when a cola was consumed, but less hazardous when red wine was consumed.

  2. Human Pharmacokinetics of High Dose Oral Curcumin and Its Effect on Heme Oxygenase-1 Expression in Healthy Male Subjects

    Directory of Open Access Journals (Sweden)

    Uros Klickovic

    2014-01-01

    Full Text Available Purpose. Heme oxygenase-1 (HO-1 has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism. Methods. In an open label uncontrolled phase-1 pilot study, ten male subjects received 12 g of oral curcumin. To investigate the effects of the GT length polymorphism on the inducibility of HO-1, five subjects with homozygous short and five with homozygous long GT genotypes were studied. Plasma concentrations of curcumin, bilirubin, HO-1 mRNA, and protein expression in peripheral blood mononuclear cells (PBMCs were analyzed over 48 hours. Results. At a detection limit of 1 µg/mL curcumin could not be detected in plasma of any subject. Compared to baseline, HO-1 mRNA and protein levels were not induced in PBMCs at any time point up to 48 hours. There was no correlation between any of the parameters and GT length polymorphism. Conclusions. Oral curcumin administration has low bioavailability and does not induce HO-1 on mRNA or protein level in PBMCs.

  3. Carica papaya increases regulatory T cells and reduces IFN-γ+ CD4+ T cells in healthy human subjects.

    Science.gov (United States)

    Abdullah, Maha; Chai, Pei-Shin; Loh, Chiew-Yee; Chong, Mun-Yee; Quay, Huai-Wei; Vidyadaran, Sharmili; Seman, Zainina; Kandiah, Mirnalini; Seow, Heng-Fong

    2011-05-01

    Fruit and vegetables have therapeutic potential as they dampen inflammation, have no known side-effects and as whole foods have prospective additive and synergistic benefits. Th1 (IFN-γ(+) CD4(+))/Th2 (IL-4(+)CD4(+)) T cells play a vital role in mediating inflammatory responses and may be regulated by regulatory T cells (Tregs). Effects of Carica papaya on cells of healthy individuals were determined using flow cytometry methods. Significant down-regulation of IFN-γ(+) CD4(+) (p=0.03, n=13), up-regulation of IL-4(+) CD4(+) (p=0.04, n=13) T cells and up-regulation of CD3(+) CD4(+) CD25(+) CD127(-) (p=0.001, n=15) Tregs were observed after papaya consumption. In vitro cultures showed up-regulation of Tregs in male subjects and was significantly associated with levels of IL-1β in culture supernatants (R(2) =0.608, p=0.04, n=12). Other inflammatory cytokines were significantly suppressed. Papaya consumption may exert an anti-inflammatory response mediated through Tregs and have potential in alleviating inflammatory conditions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Inflammatory and Oxidative Stress Responses to High-Carbohydrate and High-Fat Meals in Healthy Humans

    Directory of Open Access Journals (Sweden)

    S. Gregersen

    2012-01-01

    Full Text Available The postprandial state is hypothesised to be proinflammatory and prooxidative, but the relative contributions of fat versus carbohydrate are unclear. Therefore, we examined inflammation and oxidative stress responses in serum and skeletal muscle before and after 1000 kcal meals, which were high in either fat or carbohydrate in 15 healthy individuals. Serum and muscle expression of IL6 was elevated 3 hours after each meal, independently of macronutrient composition (P<0.01. Serum IL18 was decreased after high-fat meal only (P<0.01. Plasma total antioxidative status and muscle Cu/Zn-superoxide dismutase were decreased after high-carbohydrate meal only (P<0.05. We conclude that a high-carbohydrate meal may evoke a greater postprandial oxidative stress response, whereas both fat and carbohydrate increased IL6. We speculate that the observed increases in postprandial IL6, without increases in any other markers of inflammation, may indicate a normal IL6 response to enhance glucose uptake, similar to its role postexercise.

  5. Bioequivalence evaluation of two roxithromycin formulations in healthy human volunteers by high performance liquid cromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Motta, M; Ribeiro, W; Ifa, D R; Moares, M E; Moraes, M O; Corrado, A P; De Nucci, G

    1999-01-01

    The bioequivalence of two different formulations containing roxithromycin (SPE-712-1). Oral suspension 300 mg/15 mL as test formulation and Rotram, tablets 300 mg as reference formulation, both by Schering Plough S.A., Brazil) was evaluated in 24 healthy volunteers of both sexes (12 male and 12 female). The study was conducted open with randomized two-period crossover design and a 14-day washout period. Each subject received 300 mg of each roxithromycin formulation. Plasma samples were obtained over a 72-hour interval and roxithromycin concentrations were analyzed by combined LC-MS/MS with positive ion electrospray ionization using selected ion monitoring method. From the plasma roxithromycin concentration vs time curves the following pharmacokinetic parameters were obtained: AUC(0-72 h), AUC(0-infinity), Cmax, t1/2 ratios and tmax individual differences. The 90% for confidence interval (CI) of geometric mean SPE-712-L/Rotram individual percent ratio were 105.0-128.3% for AUC(0-72 h), and 78.4-96.9 for Cmax. Although this 90% CI were marginally outside the interval proposed by the Food and Drug Administration, the probability assessed by the two-one sided West for ratios was included in the 0.8-1.25 interval, as we concluded that SPE-712-L oral suspension formulation was bioequivalent to Rotram tablet formulation for the extent and rate of absorption.

  6. The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2011-01-01

    Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.......Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents....

  7. The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2011-01-01

    Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.......Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents....

  8. 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)

  9. 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.

  10. Evaluation of calcium, magnesium, potassium and sodium in biological samples of male human immunodeficiency virus patients with tuberculosis and diarrhea compared to healthy control subjects in Pakistan.

    Science.gov (United States)

    Afridi, Hassan Imran; Kazi, Tasneem Gul; Talpur, Farah Naz; Kazi, Naveed; Naeemullah, Faheem Shah; Arain, Sadaf Sadia; Brahman, Kapil Dev

    2013-01-01

    Electrolyte deficiency has been associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) disease progression and mortality. This study examined the association between low electrolyte concentrations in blood and scalp hair and the presence of opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Sixty-two male HIV positive patients (HIV-1) from various cities in Pakistan were recruited to the study. These Patients were divided into two groups according to secondary infections (tuberculosis and high fever with diarrhea), and biological samples (scalp hair, serum, blood and urine) were collected from them. As a comparative control group, 120 healthy subjects (males) of the same age group (31 - 45 years), socio-economic status, localities and dietary habits were also included in the study. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry after microwave-assisted acid digestion. Validity and accuracy of the methodology were checked using certified reference materials (CRMs) and against values obtained by a conventional wet acid digestion method on the same CRMs. The results indicated significantly lower levels of calcium, potassium, magnesium and natrium in all analyzed biological samples (blood, serum and scalp hair) of male patients with Acquired Immune Deficiency Syndrome (AIDS) in comparison to healthy controls (p < 0.01), while the levels of these elements were found to be higher in urine samples of the AIDS patients than in those of the control group. These data offer guidance to clinicians and other professionals investigating the deficiency of electrolytes in biological samples (scalp hair, serum and blood) of AIDS patients in relation to healthy subjects.

  11. Prevalence of cervical human papillomavirus infection in healthy women is related to sexual behaviours and educational level: a cross-sectional study.

    Science.gov (United States)

    Tay, Sun Kuie; Oon, Lynette Lin Ean

    2014-12-01

    This study reports the prevalence and risk factors of human papillomavirus (HPV) infection in healthy women in Singapore. Demography, education, sexual and reproductive history and cigarette smoking habits were obtained from a cross-sectional population of healthy women and girls aged above 12 years of age. Cervical or vaginal cytology samples were investigated for 37 known anogenital HPV subtypes using the linear array PCR method. Chi square statistics were used to test for associations of individual epidemiological factors with HPV infection. Independent risk factors were identified with binomial logistic regression analysis. Of 891 subjects, the prevalence of HPV infection was 9.31% (83/891 women) for any-type HPV and 5.05% (46/891 women) for the high-risk HPV (hrHPV). Of 30 HPV subtypes detected, the most prevalent genotypes in descending order of frequency were subtypes 51, 16, 52, 58 and 66 for hrHPV and subtypes 62, 61, 84, 72 and 53 for the low-risk HPV. This frequency distribution of HPV subtypes was different from reports from other countries within Asia. Forty-six virgins studied tested negative for HPV infection. Significant independent risk factors for any-type HPV infection were multiple sexual partners (adjusted OR 1.4) and low (≤6 years) educational level (adjusted OR 4.0). The distribution of HPV subtypes in healthy women varies between different countries within Asia. In Singapore, the prevalence of HPV infection was 9.31% and was related to penetrative sexual intercourse, multiple sexual partners and low educational level.

  12. Magnetization transfer in human achilles tendon assessed by a 3D ultrashort echo time sequence. Quantitative examinations in healthy volunteers at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Syha, R.; Grosse, U.; Springer, F. [Tuebingen Univ. (Germany). Diagnostic and Interventional Radiology; Tuebingen Univ. (Germany). Section on Experimental Radiology; Martirosian, P.; Schick, F. [Tuebingen Univ. (Germany). Section on Experimental Radiology; Ketelsen, D.; Claussen, C.D. [Tuebingen Univ. (Germany). Diagnostic and Interventional Radiology

    2011-11-15

    Magnetization transfer contrast (MTC) imaging provides insight into interactions between free and bounded water. Newly developed ultrashort echo time (UTE) sequences implemented on whole-body magnetic resonance (MR) scanners allow MTC imaging in tissues with extremely fast signal decay such as tendons. The aim of this study was to develop a technique for the quantification of the MT effect in healthy Achilles tendons in-vivo at 3 Tesla. 16 normal tendons of volunteers with no history of tendinopathy were examined using a 3D-UTE sequence with a rectangular on-resonant excitation pulse and a Fermi-shaped off-resonant MT preparation pulse. The frequency of the MT pulse was varied from 1 to 5 kHz. MT effects were calculated in terms of the MT ratio (MTR) between measurements without and with MT preparation. Direct saturation effects of MT preparation on the signal intensity were evaluated using numerical simulation of Bloch equations. One patient with tendinopathy was examined to exemplarily show changes of MTR under pathologic conditions. Calculation of MTR data was feasible in all examined tendons and showed a decrease from 0.53 {+-} 0.05 to 0.25 {+-} 0.03 (1 kHz to 5 kHz) for healthy volunteers. Evaluation of variation with gender and dominance of ankle revealed no significant differences (p > 0.05). In contrast, the patient with confirmed tendinopathy showed MTR values between 0.36 (1 kHz) and 0.19 (5 kHz). MT effects in human Achilles tendons can be reliably assessed in-vivo using a 3D UTE sequence at 3 T. All healthy tendons showed similar MTR values (coefficient of variation 10.0 {+-} 1.2 %). The examined patient showed a clearly different MT effect revealing a changed microstructure in the case of tendinopathy. (orig.)

  13. Development and characterization of twelve microsatellite markers for Porphyra linearis Greville.

    Science.gov (United States)

    Varela-Álvarez, Elena; Paulino, Cristina; Serrão, Ester A

    2017-02-01

    The genus Porphyra (and its sister genus Pyropia) contains important red algal species that are cultivated and/or harvested for human consumption, sustaining a billion-dollar aquaculture industry. A vast amount of research has been focused on species of this genus, including studies on genetics and genomics among other areas. Twelve novel microsatellite markers were developed here for Porphyra linearis. Markers were characterized using 32 individuals collected from four natural populations of P. linearis with total heterozygosity varying from 0.098 to 0.916. The number of alleles per locus ranged from 2 to 18. All markers showed cross amplification with Porphyra umbilicalis and/or Porphyra dioica. These polymorphic microsatellite markers are useful for investigating population genetic diversity and differentiation in P. linearis and may become useful for other genetic research on the reproductive biology of this important species.

  14. Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B W

    2016-01-01

    BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we record...... cortex. Sumatriptan injection reversed these changes. CONCLUSION: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.......BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...

  15. A randomised, double- blind, cross-over study investigating the prebiotic effect of agave fructans in healthy human subjects

    OpenAIRE

    Ramnani, Priya; Costabile, Adele; Bustillo, A. G. R.; Gibson, Glenn R.

    2015-01-01

    This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal ...

  16. High-Caloric and Chocolate Stimuli Processing in Healthy Humans: An Integration of Functional Imaging and Electrophysiological Findings

    OpenAIRE

    Deyar Asmaro; Mario Liotti

    2014-01-01

    There has been a great deal of interest in understanding how the human brain processes appetitive food cues, and knowing how such cues elicit craving responses is particularly relevant when current eating behavior trends within Westernized societies are considered. One substance that holds a special place with regard to food preference is chocolate, and studies that used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have identified neural regions and electr...

  17. 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

  18. Effects of geomagnetic activity variations on the physiological and psychological state of functionally healthy humans: Some results of Azerbaijani studies

    Science.gov (United States)

    Babayev, Elchin S.; Allahverdiyeva, Aysel A.

    There are collaborative and cross-disciplinary space weather studies in the Azerbaijan National Academy of Sciences conducted with purposes of revealing possible effects of solar, geomagnetic and cosmic ray variability on certain technological, biological and ecological systems. This paper describes some results of the experimental studies of influence of the periodical and aperiodical changes of geomagnetic activity upon human brain, human health and psycho-emotional state. It also covers the conclusions of studies on influence of violent solar events and severe geomagnetic storms of the solar cycle 23 on the mentioned systems in middle-latitude location. It is experimentally established that weak and moderate geomagnetic storms do not cause significant changes in the brain's bioelectrical activity and exert only stimulating influence while severe disturbances of geomagnetic conditions cause negative influence, seriously disintegrate brain's functionality, activate braking processes and amplify the negative emotional background of an individual. It is concluded that geomagnetic disturbances affect mainly emotional and vegetative spheres of human beings while characteristics reflecting personality properties do not undergo significant changes.

  19. Neuropsychology of environmental navigation in humans: review and meta-analysis of FMRI studies in healthy participants.

    Science.gov (United States)

    Boccia, Maddalena; Nemmi, Federico; Guariglia, Cecilia

    2014-06-01

    In the past 20 years, many studies in the cognitive neurosciences have analyzed human ability to navigate in recently learned and familiar environments by investigating the cognitive processes involved in successful navigation. In this study, we reviewed the main experimental paradigms and made a cognitive-oriented meta-analysis of fMRI studies of human navigation to underline the importance of the experimental designs and cognitive tasks used to assess navigational skills. We performed a general activation likelihood estimation (ALE) meta-analysis of 66 fMRI experiments to identify the neural substrates underpinning general aspects of human navigation. Four individual ALE analyses were performed to identify the neural substrates of different experimental paradigms (i.e., familiar vs. recently learned environments) and different navigational strategies (allocentric vs. egocentric). Results of the general ALE analysis highlighted a wide network of areas with clusters in the occipital, parietal, frontal and temporal lobes, especially in the parahippocampal cortex. Familiar environments seem to be processed by an extended temporal-frontal network, whereas recently learned environments require activation in the parahippocampal cortex and the parietal and occipital lobes. Allocentric strategy is subtended by the same areas as egocentric strategy, but the latter elicits greater activation in the right precuneus, middle occipital lobe and angular gyrus. Our results suggest that different neural correlates are involved in recalling a well-learned or recently acquired environment and that different networks of areas subtend egocentric and allocentric strategies.

  20. Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl in Human Healthy Volunteers: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Rocío García-Villalba

    2015-12-01

    Full Text Available The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives.

  1. Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.

    Science.gov (United States)

    Huang, Yu; Yang, Lu; Wang, Jianchun; Yang, Fan; Xiao, Ying; Xia, Rongjun; Yuan, Xianhou; Yan, Mingshan

    2013-09-01

    Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized mainly by progressive cerebellar ataxia, oculocutaneous telangiectasia, and immunodeficiency. This disease is caused by mutations of the ataxia telangiectasia mutated (Atm) gene. More than 500 Atm mutations that are responsible for A-T have been identified so far. However, there have been very few A-T cases reported in China, and only two Chinese A-T patients have undergone Atm gene analysis. In order to systemically investigate A-T in China and map their Atm mutation spectrum, we recruited eight Chinese A-T patients from six unrelated families nationwide. Using direct sequencing of genomic DNA and the multiplex ligation-dependent probe amplification, we identified twelve pathogenic Atm mutations, including one missense, four nonsense, five frameshift, one splicing, and one large genomic deletion. All the Atm mutations we identified were novel, and no homozygous mutation and founder-effect mutation were found. These results suggest that Atm mutations in Chinese populations are diverse and distinct largely from those in other ethnic areas.

  2. Oral papillary squamous cell carcinoma in twelve dogs.

    Science.gov (United States)

    Nemec, A; Murphy, B G; Jordan, R C; Kass, P H; Verstraete, F J M

    2014-01-01

    Papillary squamous cell carcinoma (PSCC) is a distinct histological subtype of oral squamous cell carcinoma (SCC), described in both dogs and man. In dogs, PSCC has long been considered a malignant oral tumour of very young animals, but it has recently been reported to occur in adult dogs as well. The aim of this study was to describe the major clinicopathological characteristics of canine oral PSCC (COPSCC). Twelve dogs diagnosed with COPSCC were included in this retrospective study (1990-2012). The majority (75%) of the dogs were >6 years of age (median age 9 years). All tumours were derived from the gingiva of dentate jaws, with 66.7% affecting the rostral aspects of the jaws. The gross appearance of the lesions varied, with one having an intraosseous component only. The majority (91.7%) of the tumours were advanced lesions (T2 and T3), but no local or distant metastases were noted. Microscopically, two patterns were seen: (1) invasion of bone forming a cup-shaped indentation in the bone or a deeply cavitating cyst within the bone (cavitating pattern), (2) histologically malignant growth, but lack of apparent bone invasion (non-cavitating pattern). The microscopical appearance corresponded to imaging findings in a majority of cases, with cavitating forms presenting with a cyst-like pattern of bone loss or an expansile mass on imaging and non-cavitating forms showing an infiltrative pattern of bone destruction on imaging. These features suggest two distinct biological behaviours of COPSCC.

  3. Sensitivity and growth of twelve Elatior begonia cultivars to ozone

    Energy Technology Data Exchange (ETDEWEB)

    Reinert, R.A.; Nelson, P.V.

    1979-12-01

    Twelve cultivars of Elatior begonia (Begonia X hiemalis Fotsch.) were exposed to O/sub 3/ at 25 and 50 pphM. The 'Schwabenland' group, 'Whisper 'O' Pink', and 'Improved Krefeld Orange' were the most sensitive, whereas 'Ballerina', 'Mikkell Limelight', and 'Turo' were the least sensitive. 'Rennaisance', 'Heirloom' 'Nixe', and 'Fantasy' were intermediate in sensitivity. The dry weight of foliage (stems plus leaves) of 9 cultivars exposed to O/sub 3/ was significantly less than that of control plants. Ozone at 25 and 50 pphM inhibited flower growth (including peduncles) and development in 4 and 8 of the 12 cultivars, respectively. Differences in flower weight ranged from 43 to 105% of the control at 25 pphM and from 25 to 98% of the control at 50 pphM, depending on cultivar. 1 table.

  4. Twelve tips for designing and running longitudinal integrated clerkships.

    Science.gov (United States)

    Ellaway, Rachel; Graves, Lisa; Berry, Sue; Myhre, Doug; Cummings, Beth-Ann; Konkin, Jill

    2013-12-01

    Longitudinal integrated clerkships (LICs) involve learners spending an extended time in a clinical setting (or a variety of interlinked clinical settings) where their clinical learning opportunities are interwoven through continuities of patient contact and care, continuities of assessment and supervision, and continuities of clinical and cultural learning. Our twelve tips are grounded in the lived experiences of designing, implementing, maintaining, and evaluating LICs, and in the extant literature on LICs. We consider: general issues (anticipated benefits and challenges associated with starting and running an LIC); logistical issues (how long each longitudinal experience should last, where it will take place, the number of learners who can be accommodated); and integration issues (how the LIC interfaces with the rest of the program, and the need for evaluation that aligns with the dynamics of the LIC model). Although this paper is primarily aimed at those who are considering setting up an LIC in their own institutions or who are already running an LIC we also offer our recommendations as a reflection on the broader dynamics of medical education and on the priorities and issues we all face in designing and running educational programs.

  5. Commercializing Government-sponsored Innovations: Twelve Successful Buildings Case Studies

    Science.gov (United States)

    Brown, M. A.; Berry, L. G.; Goel, R. K.

    1989-01-01

    This report examines the commercialization and use of R and D results funded by DOE's Office of Buildings and Community Systems (OBCS), an office that is dedicated to improving the energy efficiency of the nation's buildings. Three goals guided the research described in this report: to improve understanding of the factors that hinder or facilitate the transfer of OBCS R and D results, to determine which technology transfer strategies are most effective and under what circumstances each is appropriate, and to document the market penetration and energy savings achieved by successfully-commercialized innovations that have received OBCS support. Twelve successfully-commercialized innovations are discussed here. The methodology employed involved a review of the literature, interviews with innovation program managers and industry personnel, and data collection from secondary sources. Six generic technology transfer strategies are also described. Of these, contracting R and D to industrial partners is found to be the most commonly used strategy in our case studies. The market penetration achieved to date by the innovations studied ranges from less than 1% to 100%. For the three innovations with the highest predicted levels of energy savings (i.e., the flame retention head oil burner, low-E windows, and solid-state ballasts), combined cumulative savings by the year 2000 are likely to approach 2 quads. To date the energy savings for these three innovations have been about 0.2 quads. Our case studies illustrate the important role federal agencies can play in commercializing new technologies.

  6. The strong coupling regime of twelve flavors QCD

    CERN Document Server

    da Silva, Tiago Nunes

    2012-01-01

    We summarize the results recently reported in Ref.[1] [A. Deuzeman, M.P. Lombardo, T. Nunes da Silva and E. Pallante,"The bulk transition of QCD with twelve flavors and the role of improvement"] for the SU(3) gauge theory with Nf=12 fundamental flavors, and we add some numerical evidence and theoretical discussion. In particular, we study the nature of the bulk transition that separates a chirally broken phase at strong coupling from a chirally restored phase at weak coupling. When a non-improved action is used, a rapid crossover is observed at small bare quark masses. Our results confirm a first order nature for this transition, in agreement with previous results we obtained using an improved action. As shown in Ref.[1], when improvement of the action is used, the transition is preceded by a second rapid crossover at weaker coupling and an exotic phase emerges, where chiral symmetry is not yet broken. This can be explained [1] by the non hermiticity of the improved lattice Transfer matrix, arising from the c...

  7. Occupancy of Nociceptin/Orphanin FQ Peptide Receptors by the Antagonist LY2940094 in Rats and Healthy Human Subjects.

    Science.gov (United States)

    Raddad, Eyas; Chappell, Amy; Meyer, Jeffery; Wilson, Alan; Ruegg, Charles E; Tauscher, Johannes; Statnick, Michael A; Barth, Vanessa; Zhang, Xin; Verfaille, Steven J

    2016-09-01

    Therapeutic benefits from nociceptin opioid peptide receptor (NOP) antagonism were proposed for obesity, eating disorders, and depression. LY2940094 ([2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol) is a novel, orally bioavailable, potent, and selective NOP antagonist. We studied NOP receptor occupancy (RO) after single oral LY2940094 doses in rat hypothalamus and human brain by use of liquid chromatography with tandem mass spectrometry (LC-MS/MS) (LSN2810397) and positron emission tomography (PET) ([(11)C]NOP-1A) tracers, respectively. A bolus plus constant infusion tracer protocol with PET was employed in humans at 2.5 and 26.5 hours after administration of the LY2940094 dose. The RO was calculated from the change in regional distributional volume (VT) corrected for nondisplaceable volume using Lasson plots. The RO followed a simple Emax relationship to plasma LY2940094 concentration, reaching near complete occupancy in both species. For rat hypothalamus, the plasma concentration at half-maximum RO (EC50) was 5.8 ng/ml. In humans, LY2940094 was well tolerated and safe over the 4-40 mg dose range, and it peaked in plasma at 2 to 6 hours after a 1- to 2-hour lag, with approximate dose-proportional exposure. After 4-40 mg doses, NOP RO was similar across the prefrontal cortex, occipital cortex, putamen, and thalamus, with EC50 of 2.94 to 3.46 ng/ml, less than 2-fold lower than in rats. Over 4-40 mg doses, LY2940094 mean plasma levels at peak and 24 hours were 7.93-102 and 1.17-14.1 ng/ml, corresponding to the cross-region average NOP RO of 73%-97% and 28%-82%, respectively. The rat EC50 translates well to humans. LY2940094 readily penetrates the human brain, and a once-daily oral dose of 40 mg achieves sustainably high (>80%) NOP RO levels suitable for testing clinical efficacy.

  8. Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

    Science.gov (United States)

    Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

    2009-08-01

    Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

  9. The effect of aging and cardiorespiratory fitness on the lung diffusing capacity response to exercise in healthy humans.

    Science.gov (United States)

    Coffman, Kirsten E; Carlson, Alex R; Miller, Andrew D; Johnson, Bruce D; Taylor, Bryan Joseph

    2017-03-23

    Aging is associated with deterioration in the structure and function of the pulmonary circulation. We characterized the lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary-capillary blood volume (VC) response to discontinuous incremental exercise at 25, 50, 75, and 90% of peak work (Wpeak) in four groups: 1) Young [27 ± 3 y, maximal oxygen consumption (V̇O2max) 110 ± 18% age-predicted]; 2) Young Highly-Fit (27 ± 3 y, V̇O2max 147 ± 8% age-predicted); 3) Old (69 ± 5 y, V̇O2max 116 ± 13% age-predicted); and 4) Old Highly-Fit (65 ± 5 y, V̇O2max 162 ± 18% age-predicted). At rest and at 90% Wpeak, DLCO, DmCO, and VC were decreased with age. At 90% Wpeak, DLCO, DmCO and VC were greater in Old Highly-Fit vs. Old adults. The slope of the DLCO-cardiac output (Q̇) relationship from rest to end-exercise at 90% Wpeak was not different between Young, Young Highly-Fit, Old and Old Highly-Fit (1.35 vs. 1.44 vs. 1.10 vs. 1.35 mlCO·mmHg(-1)·Lblood(-1), P = 0.388), with no evidence of a plateau in this relationship during exercise; this was also true for DmCO-Q̇ and VC-Q̇. V̇O2max was positively correlated with: 1) DLCO, DmCO, and VC at rest; 2) the rest to end-exercise change in DLCO, DmCO, and VC In conclusion, these data suggest that despite the age-associated deterioration in the structure and function of the pulmonary circulation, expansion of the pulmonary capillary network does not become limited during exercise in healthy individuals regardless of age or cardiorespiratory fitness level.

  10. High throughput measurement of γH2AX DSB repair kinetics in a healthy human population.

    Science.gov (United States)

    Sharma, Preety M; Ponnaiya, Brian; Taveras, Maria; Shuryak, Igor; Turner, Helen; Brenner, David J

    2015-01-01

    The Columbia University RABiT (Rapid Automated Biodosimetry Tool) quantifies DNA damage using fingerstick volumes of blood. One RABiT protocol quantifies the total γ-H2AX fluorescence per nucleus, a measure of DNA double strand breaks (DSB) by an immunofluorescent assay at a single time point. Using the recently extended RABiT system, that assays the γ-H2AX repair kinetics at multiple time points, the present small scale study followed its kinetics post irradiation at 0.5 h, 2 h, 4 h, 7 h and 24 h in lymphocytes from 94 healthy adults. The lymphocytes were irradiated ex vivo with 4 Gy γ rays using an external Cs-137 source. The effect of age, gender, race, ethnicity, alcohol use on the endogenous and post irradiation total γ-H2AX protein yields at various time points were statistically analyzed. The endogenous γ-H2AX levels were influenced by age, race and alcohol use within Hispanics. In response to radiation, induction of γ-H2AX yields at 0.5 h and peak formation at 2 h were independent of age, gender, ethnicity except for race and alcohol use that delayed the peak to 4 h time point. Despite the shift in the peak observed, the γ-H2AX yields reached close to baseline at 24 h for all groups. Age and race affected the rate of progression of the DSB repair soon after the yields reached maximum. Finally we show a positive correlation between endogenous γ-H2AX levels with radiation induced γ-H2AX yields (RIY) (r=0.257, P=0.02) and a negative correlation with residuals (r=-0.521, P=DSB γ-H2AX repair kinetics as measured by RABiT immunofluorescent assay.

  11. In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects.

    Science.gov (United States)

    Kanegawa, Naoki; Collste, Karin; Forsberg, Anton; Schain, Martin; Arakawa, Ryosuke; Jucaite, Aurelija; Lekander, Mats; Olgart Höglund, Caroline; Kosek, Eva; Lampa, Jon; Halldin, Christer; Farde, Lars; Varrone, Andrea; Cervenka, Simon

    2016-05-01

    Microglia, the resident macrophages in the central nervous system, are thought to be maintained by a local self-renewal mechanism. Although preclinical and in vitro studies have suggested that the brain may contain immune cells also from peripheral origin, the functional association between immune cells in the periphery and brain at physiological conditions is poorly understood. We examined 32 healthy individuals using positron emission tomography (PET) and [(11)C]PBR28, a radioligand for the 18-kDa translocator protein (TSPO) which is expressed both in brain microglia and blood immune cells. In 26 individuals, two measurements were performed with varying time intervals. In a subgroup of 19 individuals, of which 12 had repeat examinations, leukocyte numbers in blood was measured on each day of PET measurements. All individuals were genotyped for TSPO polymorphism and categorized as high, mixed, and low affinity binders. We assessed TSPO binding expressed as total distribution volume of [(11)C]PBR28 in brain and in blood cells. TSPO binding in brain was strongly and positively correlated to binding in blood cells both at baseline and when analyzing change between two PET examinations. Furthermore, there was a significant correlation between change of leukocyte numbers and change in TSPO binding in brain, and a trend-level correlation to change in TSPO binding in blood cells. These in vivo findings indicate an association between immunological cells in blood and brain via intact BBB, suggesting a functional interaction between these two compartments, such as interchange of peripherally derived cells or a common regulatory mechanism. Measurement of radioligand binding in blood cells may be a way to control for peripheral immune function in PET studies using TSPO as a marker of brain immune activation.

  12. Prevalence of high-risk human papillomavirus types 16 and 18 in healthy women with cytologically negative pap smear in Iran

    Directory of Open Access Journals (Sweden)

    Safaei Akbar

    2010-10-01

    Full Text Available Background: Because human papillomavirus (HPV is one of the causal factors in cervical cancer, understanding the epidemiology of this infection is an important step towards developing strategies for prevention. Materials and Methods: We evaluated the prevalence of high-risk human papillomavirus Types 16 and 18 in cervical samples from 402 healthy women with normal Pap smears by testing with type-specific primers in the polymerase chain reaction. Participants were seen at two gynecological clinics affiliated to the Shiraz University of Medical Sciences in Iran. Result: The prevalence of positive HPV findings was 5.5%; high-risk HPV human papillomavirus Type 16 prevalence was 2% and no patient harbored HPV-18. The prevalence of HPV was 4.5% in younger age group and gradually increased to 20% in the 4 th decade. Conclusion: The prevalence of high-risk HPV was highest in the youngest women and gradually decreased with age. Overall, the prevalence of HPV in our population is low.

  13. Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors

    Directory of Open Access Journals (Sweden)

    Targoni Oleg S

    2005-06-01

    Full Text Available Abstract Background One means of treating osteoarthritis is with autologous or allogeneic osteochondral grafts. The purpose of this study was to evaluate the innate immunological response in humans toward xeno-derived osteochondral grafts that have been partially or entirely treated by the photooxidation process. Methods The antigens tested included bovine, porcine, ovine and equine osteochondral samples that have been treated in successive steps of photooxidation. ELISPOT assays were used to evaluate the production of IL-1, IL-4, IL-6, IL-10, IL-12 and TNF-α by human monocytes in response to the antigens. Results Results indicated vigorous production of IL-1, IL-6, IL-10 and TNF-α in response to untreated bovine, porcine and equine specimens. This indicates that these samples are perceived as foreign, or stimulatory, by the human monocytes. There was no induction of IL-4 or IL-12, which is required for Th2 and Th1 immunity, respectively. In contrast, the processed bovine, porcine and equine samples did not induce significant activation of cells of the innate immune system. This occurred after the first step in processing (after cleaning in increasing strengths of ethanol. This suggests that the processing steps dramatically, if not completely, negated the immunostimulatory properties of the test sample. The results for the ovine samples indicate a reverse response. Conclusion The findings of the study suggest that photooxidized bovine, porcine or equine samples have the potential to be used as an osteochondral graft. Although the first step in processing reduced the immunological response, photooxidation is still necessary to retain the structure and mechanical integrity of the cartilage, which would allow for immediate joint resurfacing.

  14. Effects of multiple-dose ponesimod, a selective S1P1 receptor modulator, on lymphocyte subsets in healthy humans

    Directory of Open Access Journals (Sweden)

    Jurcevic S

    2016-12-01

    Full Text Available Stipo Jurcevic,1 Pierre-Eric Juif,2 Colleen Hamid,3 Roseanna Greenlaw,3 Daniele D’Ambrosio,2 Jasper Dingemanse2 1Department of Biomedical Sciences, University of Westminster, London, UK; 2Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland; 3Division of Transplantation Immunology & Mucosal Biology, King’s College London, London, UK Abstract: This study investigated the effects of ponesimod, a selective S1P1 receptor modulator, on T lymphocyte subsets in 16 healthy subjects. Lymphocyte subset proportions and absolute numbers were determined at baseline and on Day 10, after once-daily administration of ponesimod (10 mg, 20 mg, and 40 mg each consecutively for 3 days or placebo (ratio 3:1. The overall change from baseline in lymphocyte count was -1,292±340×106 cells/L and 275±486×106 cells/L in ponesimod- and placebo-treated subjects, respectively. This included a decrease in both T and B lymphocytes following ponesimod treatment. A decrease in naïve CD4+ T cells (CD45RA+CCR7+ from baseline was observed only after ponesimod treatment (-113±98×106 cells/L, placebo: 0±18×106 cells/L. The number of T-cytotoxic (CD3+CD8+ and T-helper (CD3+CD4+ cells was significantly altered following ponesimod treatment compared with placebo. Furthermore, ponesimod treatment resulted in marked decreases in CD4+ T-central memory (CD45RA-CCR7+ cells (-437±164×106 cells/L and CD4+ T-effector memory (CD45RA-CCR7- cells (-131±57×106 cells/L. In addition, ponesimod treatment led to a decrease of -228±90×106 cells/L of gut-homing T cells (CLA-integrin β7+. In contrast, when compared with placebo, CD8+ T-effector memory and natural killer (NK cells were not significantly reduced following multiple-dose administration of ponesimod. In summary, ponesimod treatment led to a marked reduction in overall T and B cells. Further investigations revealed that the number of CD4+ cells was dramatically reduced, whereas

  15. High throughput measurement of γH2AX DSB repair kinetics in a healthy human population.

    Directory of Open Access Journals (Sweden)

    Preety M Sharma

    Full Text Available The Columbia University RABiT (Rapid Automated Biodosimetry Tool quantifies DNA damage using fingerstick volumes of blood. One RABiT protocol quantifies the total γ-H2AX fluorescence per nucleus, a measure of DNA double strand breaks (DSB by an immunofluorescent assay at a single time point. Using the recently extended RABiT system, that assays the γ-H2AX repair kinetics at multiple time points, the present small scale study followed its kinetics post irradiation at 0.5 h, 2 h, 4 h, 7 h and 24 h in lymphocytes from 94 healthy adults. The lymphocytes were irradiated ex vivo with 4 Gy γ rays using an external Cs-137 source. The effect of age, gender, race, ethnicity, alcohol use on the endogenous and post irradiation total γ-H2AX protein yields at various time points were statistically analyzed. The endogenous γ-H2AX levels were influenced by age, race and alcohol use within Hispanics. In response to radiation, induction of γ-H2AX yields at 0.5 h and peak formation at 2 h were independent of age, gender, ethnicity except for race and alcohol use that delayed the peak to 4 h time point. Despite the shift in the peak observed, the γ-H2AX yields reached close to baseline at 24 h for all groups. Age and race affected the rate of progression of the DSB repair soon after the yields reached maximum. Finally we show a positive correlation between endogenous γ-H2AX levels with radiation induced γ-H2AX yields (RIY (r=0.257, P=0.02 and a negative correlation with residuals (r=-0.521, P=<0.0001. A positive correlation was also observed between RIY and DNA repair rate (r=0.634, P<0.0001. Our findings suggest age, race, ethnicity and alcohol use influence DSB γ-H2AX repair kinetics as measured by RABiT immunofluorescent assay.

  16. Effects of multiple-dose ponesimod, a selective S1P1 receptor modulator, on lymphocyte subsets in healthy humans

    Science.gov (United States)

    Jurcevic, Stipo; Juif, Pierre-Eric; Hamid, Colleen; Greenlaw, Roseanna; D’Ambrosio, Daniele; Dingemanse, Jasper

    2017-01-01

    This study investigated the effects of ponesimod, a selective S1P1 receptor modulator, on T lymphocyte subsets in 16 healthy subjects. Lymphocyte subset proportions and absolute numbers were determined at baseline and on Day 10, after once-daily administration of ponesimod (10 mg, 20 mg, and 40 mg each consecutively for 3 days) or placebo (ratio 3:1). The overall change from baseline in lymphocyte count was −1,292±340×106 cells/L and 275±486×106 cells/L in ponesimod- and placebo-treated subjects, respectively. This included a decrease in both T and B lymphocytes following ponesimod treatment. A decrease in naïve CD4+ T cells (CD45RA+CCR7+) from baseline was observed only after ponesimod treatment (−113±98×106 cells/L, placebo: 0±18×106 cells/L). The number of T-cytotoxic (CD3+CD8+) and T-helper (CD3+CD4+) cells was significantly altered following ponesimod treatment compared with placebo. Furthermore, ponesimod treatment resulted in marked decreases in CD4+ T-central memory (CD45RA−CCR7+) cells (−437±164×106 cells/L) and CD4+ T-effector memory (CD45RA−CCR7−) cells (−131±57×106 cells/L). In addition, ponesimod treatment led to a decrease of −228±90×106 cells/L of gut-homing T cells (CLA−integrin β7+). In contrast, when compared with placebo, CD8+ T-effector memory and natural killer (NK) cells were not significantly reduced following multiple-dose administration of ponesimod. In summary, ponesimod treatment led to a marked reduction in overall T and B cells. Further investigations revealed that the number of CD4+ cells was dramatically reduced, whereas CD8+ and NK cells were less affected, allowing the body to preserve critical viral-clearing functions. PMID:28096659

  17. Safety analysis of a Russian phage cocktail: From MetaGenomic analysis to oral application in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    McCallin, Shawna, E-mail: semccallin@yahoo.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Alam Sarker, Shafiqul, E-mail: sasarker@icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Barretto, Caroline, E-mail: Caroline.Barretto@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Sultana, Shamima, E-mail: shamima@icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Berger, Bernard, E-mail: bernard.berger@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Huq, Sayeda, E-mail: sayeeda@mail.icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Krause, Lutz, E-mail: ltz.krause@gmail.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Bibiloni, Rodrigo, E-mail: Rodrigo.Bibiloni@agresearch.co.nz [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Schmitt, Bertrand, E-mail: bertrand.schmitt@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Reuteler, Gloria, E-mail: gloria.reuteler@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Brüssow, Harald, E-mail: harald.bruessow@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)

    2013-09-01

    Phage therapy has a long tradition in Eastern Europe, where preparations are comprised of complex phage cocktails whose compositions have not been described. We investigated the composition of a phage cocktail from the Russian pharmaceutical company Microgen targeting Escherichia coli/Proteus infections. Electron microscopy identified six phage types, with numerically T7-like phages dominating over T4-like phages. A metagenomic approach using taxonomical classification, reference mapping and de novo assembly identified 18 distinct phage types, including 7 genera of Podoviridae, 2 established and 2 proposed genera of Myoviridae, and 2 genera of Siphoviridae. De novo assembly yielded 7 contigs greater than 30 kb, including a 147-kb Myovirus genome and a 42-kb genome of a potentially new phage. Bioinformatic analysis did not reveal undesired genes and a small human volunteer trial did not associate adverse effects with oral phage exposure. - Highlights: • We analyzed the composition of a commercial Russian phage cocktail. • The cocktail consists of at least 10 different phage genera. • No undesired genes were detected. • No adverse effects were seen upon oral application in a small human clinical trial.

  18. Polarity-specific cortical effects of transcranial direct current stimulation in primary somatosensory cortex of healthy humans

    Directory of Open Access Journals (Sweden)

    Robert eRehmann

    2016-05-01

    Full Text Available Transcranial direct current stimulation (tDCS is a noninvasive stimulation method that has been shown to modulate the excitability of the motor and visual cortices in human subjects in a polarity dependent manner in previous studies. The aim of our study was to investigate whether anodal and cathodal tDCS can also be used to modulate the excitability of the human primary somatosensory cortex (S1. We measured paired-pulse suppression (PPS of somatosensory evoked potentials in 36 right-handed volunteers before and after anodal, cathodal or sham stimulation over the right non-dominant S1. Paired-pulse stimulation of the median nerve was performed at the dominant and non-dominant hand. After anodal tDCS, PPS was reduced in the ipsilateral S1 compared to sham stimulation, indicating an excitatory effect of anodal tDCS. In contrast, PPS in the stimulated left hemisphere was increased after cathodal tDCS, indicating an inhibitory effect of cathodal tDCS. Sham stimulation induced no pre-post differences. Thus, tDCS can be used to modulate the excitability of S1 in polarity-dependent manner, which can be assessed by paired-pulse suppression. An interesting topic for further studies could be the investigation of direct correlations between sensory changes and excitability changes induced by tDCS.

  19. Development and aging of the healthy human brain uncinate fasciculus across the lifespan using diffusion tensor tractography.

    Science.gov (United States)

    Hasan, Khader M; Iftikhar, Amal; Kamali, Arash; Kramer, Larry A; Ashtari, Manzar; Cirino, Paul T; Papanicolaou, Andrew C; Fletcher, Jack M; Ewing-Cobbs, Linda

    2009-06-18

    The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject's intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

  20. Differential responses of healthy and chronic obstructive pulmonary diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM4.

    Science.gov (United States)

    Leclercq, B; Happillon, M; Antherieu, S; Hardy, E M; Alleman, L Y; Grova, N; Perdrix, E; Appenzeller, B M; Lo Guidice, J-M; Coddeville, P; Garçon, G

    2016-11-01

    While the knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects is still incomplete, detailed in vitro studies are highly needed. With the aim of getting closer to the human in vivo conditions and better integrating a number of factors related to pre-existing chronic pulmonary inflammatory, we sought to develop primary cultures of normal human bronchial epithelial (NHBE) cells and chronic obstructive pulmonary disease (COPD)-diseased human bronchial epithelial (DHBE) cells, grown at the air-liquid interface. Pan-cytokeratin and MUC5AC immunostaining confirmed the specific cell-types of both these healthy and diseased cell models and showed they are closed to human bronchial epithelia. Thereafter, healthy and diseased cells were repeatedly exposed to air pollution-derived PM4 at the non-cytotoxic concentration of 5 μg/cm(2). The differences between the oxidative and inflammatory states in non-exposed NHBE and COPD-DHBE cells indicated that diseased cells conserved their specific physiopathological characteristics. Increases in both oxidative damage and cytokine secretion were reported in repeatedly exposed NHBE cells and particularly in COPD-DHBE cells. Diseased cells repeatedly exposed had lower capacities to metabolize the organic chemicals-coated onto the air-pollution-derived PM4, such as benzo[a]pyrene (B[a]P), but showed higher sensibility to the formation of OH-B[a]P DNA adducts, because their diseased state possibly affected their defenses. Differential profiles of epigenetic hallmarks (i.e., global DNA hypomethylation, P16 promoter hypermethylation, telomere length shortening, telomerase activation, and histone H3 modifications) occurred in repeatedly exposed NHBE and particularly in COPD-DHBE cells. Taken together, these results closely supported the highest responsiveness of COPD-DHBE cells to a repeated exposure to air pollution-derived PM4. The use of these innovative in

  1. (31)P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH, and T1 relaxation times.

    Science.gov (United States)

    Ren, Jimin; Sherry, A Dean; Malloy, Craig R

    2015-11-01

    The conventional method for measuring brain ATP synthesis is (31)P saturation transfer (ST), a technique typically dependent on prolonged pre-saturation with γ-ATP. In this study, ATP synthesis rate in resting human brain is evaluated using EBIT (exchange kinetics by band inversion transfer), a technique based on slow recovery of γ-ATP magnetization in the absence of B1 field following co-inversion of PCr and ATP resonances with a short adiabatic pulse. The unidirectional rate constant for the Pi → γ-ATP reaction is 0.21 ± 0.04 s(-1) and the ATP synthesis rate is 9.9 ± 2.1 mmol min(-1)  kg(-1) in human brain (n = 12 subjects), consistent with the results by ST. Therefore, EBIT could be a useful alternative to ST in studying brain energy metabolism in normal physiology and under pathological conditions. In addition to ATP synthesis, all detectable (31)P signals are analyzed to determine the brain concentration of phosphorus metabolites, including UDPG at around 10 ppm, a previously reported resonance in liver tissues and now confirmed in human brain. Inversion recovery measurements indicate that UDPG, like its diphosphate analogue NAD, has apparent T1 shorter than that of monophosphates (Pi, PMEs, and PDEs) but longer than that of triphosphate ATP, highlighting the significance of the (31)P-(31)P dipolar mechanism in T1 relaxation of polyphosphates. Another interesting finding is the observation of approximately 40% shorter T1 for intracellular Pi relative to extracellular Pi, attributed to the modulation by the intracellular phosphoryl exchange reaction Pi ↔ γ-ATP. The sufficiently separated intra- and extracellular Pi signals also permit the distinction of pH between intra- and extracellular environments (pH 7.0 versus pH 7.4). In summary, quantitative (31)P MRS in combination with ATP synthesis, pH, and T1 relaxation measurements may offer a promising tool to detect biochemical alterations at early stages of brain dysfunctions and diseases.

  2. [Twelve years of working of Brazzaville cancer registry].

    Science.gov (United States)

    Nsondé Malanda, Judith; Nkoua Mbon, Jean Bernard; Bambara, Augustin Tozoula; Ibara, Gérard; Minga, Benoît; Nkoua Epala, Brice; Gombé Mbalawa, Charles

    2013-02-01

    The Brazzaville cancer registry was created in 1996 with the support of the International Agency Research against Cancer (IARC) which is located in Lyon, France. The Brazzaville cancer registry is a registry which is based on population which records new cancer cases occurring in Brazzaville by using Canreg 4.0 Software. Its aim is to supply useful information to fight against cancer to physicians and to decision makers. We conducted this study whose target was to determine the incidence of cancer in Brazzaville during twelve years, from January 1st, 1998 to December 31, 2009. During that period 6,048 new cancer cases were recorded: 3,377 women (55.8%), 2,384 men (39.4%), and 287 children (4.8%) from 0 to 14 years old with an annual average of 504 cases. Middle age to the patient's diagnosis was 49.5 years in female sex and 505.5 years old for male sex. The incidence rate of cancers in Brazzaville was 39.8 or 100.000 inhabitants per year and by sex we observed 49 to female sex and 35.2 for male sex. The first cancers localizations observed to women were in order of frequency: breast, cervix uterine, liver ovaries, hematopoietic system, to men : liver, prostate, hematopoietic system, colon and stomach; to children : retina, kidney, hematopoietic system, liver and bones. These rates are the basis to know the burden of cancer among all pathologies of Brazzaville and the achievement of a national cancer control program.

  3. Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.

    Science.gov (United States)

    De Lonlay, P; Benelli, C; Fouque, F; Ganguly, A; Aral, B; Dionisi-Vici, C; Touati, G; Heinrichs, C; Rabier, D; Kamoun, P; Robert, J J; Stanley, C; Saudubray, J M

    2001-09-01

    Hyperinsulinism and hyperammonemia syndrome has been reported as a cause of moderately severe hyperinsulinism with diffuse involvement of the pancreas. The disorder is caused by gain of function mutations in the GLUD1 gene, resulting in a decreased inhibitory effect of guanosine triphosphate on the glutamate dehydrogenase (GDH) enzyme. Twelve unrelated patients (six males, six females) with hyperinsulinism and hyperammonemia syndrome have been investigated. The phenotypes were clinically heterogeneous, with neonatal and infancy-onset hypoglycemia and variable responsiveness to medical (diazoxide) and dietary (leucine-restricted diet) treatment. Hyperammonemia (90-200 micromol/L, normal carbamylglutamate administration. The patients had mean basal GDH activity (18.3 +/- 0.9 nmol/min/mg protein) not different from controls (17.9 +/- 1.8 nmol/min/mg protein) in cultured lymphoblasts. The sensitivity of GDH activity to inhibition by guanosine triphosphate was reduced in all patient lymphoblast cultures (IC(50), or concentrations required for 50% inhibition of GDH activity, ranging from 140 to 580 nM, compared with control IC(50) value of 83 +/- 1.0 nmol/L). The allosteric effect of ADP was within the normal range. The activating effect of leucine on GDH activity varied among the patients, with a significant decrease of sensitivity that was correlated with the negative clinical response to a leucine-restricted diet in plasma glucose levels in four patients. Molecular studies were performed in 11 patients. Heterozygous mutations were localized in the antenna region (four patients in exon 11, two patients in exon 12) as well as in the guanosine triphosphate binding site (two patients in exon 6, two patients in exon 7) of the GLUD1 gene. No mutation has been found in one patient after sequencing the exons 5-13 of the gene.

  4. Commercializing government-sponsored innovations: Twelve successful buildings case studies

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.A.; Berry, L.G.; Goel, R.K.

    1989-01-01

    This report examines the commercialization and use of R and D results funded by DOE's Office of Buildings and Community Systems (OBCS), an office that is dedicated to improving the energy efficiency of the nation's buildings. Three goals guided the research described in this report: to improve understanding of the factors that hinder or facilitate the transfer of OBCS R and D results, to determine which technology transfer strategies are most effective and under what circumstances each is appropriate, and to document the market penetration and energy savings achieved by successfully-commercialized innovations that have received OBCS support. Twelve successfully-commercialized innovations are discussed here. The methodology employed involved a review of the literature, interviews with innovation program managers and industry personnel, and data collection from secondary sources. Six generic technology transfer strategies are also described. Of these, contracting R and D to industrial partners is found to be the most commonly used strategy in our case studies. The market penetration achieved to date by the innovations studied ranges from less than 1% to 100%. For the three innovations with the highest predicted levels of energy savings (i.e., the flame retention head oil burner, low-E windows, and solid-state ballasts), combined cumulative savings by the year 2000 are likely to approach 2 quads. To date the energy savings for these three innovations have been about 0.2 quads. Our case studies illustrate the important role federal agencies can play in commercializing new technologies. 27 refs., 21 figs., 4 tabs.

  5. Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects.

    Science.gov (United States)

    McCallin, Shawna; Alam Sarker, Shafiqul; Barretto, Caroline; Sultana, Shamima; Berger, Bernard; Huq, Sayeda; Krause, Lutz; Bibiloni, Rodrigo; Schmitt, Bertrand; Reuteler, Gloria; Brüssow, Harald

    2013-09-01

    Phage therapy has a long tradition in Eastern Europe, where preparations are comprised of complex phage cocktails whose compositions have not been described. We investigated the composition of a phage cocktail from the Russian pharmaceutical company Microgen targeting Escherichia coli/Proteus infections. Electron microscopy identified six phage types, with numerically T7-like phages dominating over T4-like phages. A metagenomic approach using taxonomical classification, reference mapping and de novo assembly identified 18 distinct phage types, including 7 genera of Podoviridae, 2 established and 2 proposed genera of Myoviridae, and 2 genera of Siphoviridae. De novo assembly yielded 7 contigs greater than 30 kb, including a 147-kb Myovirus genome and a 42-kb genome of a potentially new phage. Bioinformatic analysis did not reveal undesired genes and a small human volunteer trial did not associate adverse effects with oral phage exposure.

  6. Is Hunting Still Healthy? Understanding the Interrelationships between Indigenous Participation in Land-Based Practices and Human-Environmental Health

    Directory of Open Access Journals (Sweden)

    Ursula King

    2014-05-01

    Full Text Available Indigenous participation in land-based practices such as hunting, fishing, ceremony, and land care has a long history. In recent years, researchers and policy makers have advocated the benefits of these practices for both Indigenous people and the places they live. However, there have also been documented risks associated with participation in these activities. Environmental change brought about by shifts in land use, climate changes, and the accumulation of contaminants in the food chain sit alongside equally rapid shifts in social, economic and cultural circumstances, preferences and practices. To date, the literature has not offered a wide-ranging review of the available cross-disciplinary or cross-ecozone evidence for these intersecting benefits and risks, for both human and environmental health and wellbeing. By utilising hunting as a case study, this paper seeks to fill part of that gap through a transdisciplinary meta-analysis of the international literature exploring the ways in which Indigenous participation in land-based practices and human-environmental health have been studied, where the current gaps are, and how these findings could be used to inform research and policy. The result is an intriguing summary of disparate research that highlights the patchwork of contradictory understandings, and uneven regional emphasis, that have been documented. A new model was subsequently developed that facilitates a more in-depth consideration of these complex issues within local-global scale considerations. These findings challenge the bounded disciplinary and geographic spaces in which much of this work has occurred to date, and opens a dialogue to consider the importance of approaching these issues holistically.

  7. Development and Application of a Blastocystis Subtype-Specific PCR Assay Reveals that Mixed-Subtype Infections Are Common in a Healthy Human Population.

    Science.gov (United States)

    Scanlan, Pauline D; Stensvold, Christen Rune; Cotter, Paul D

    2015-06-15

    The human gut is host to a diversity of microorganisms, including the single-celled microbial eukaryote Blastocystis. Research has shown that most carriers host a single Blastocystis subtype (ST), which is unusual given the considerable within-host species diversity observed for other microbial genera in this ecosystem. However, our limited knowledge of both the incidence and biological significance of Blastocystis diversity within hosts (i.e., so-called mixed infections) is likely due to problems with existing methodologies. Here, we developed and applied Blastocystis ST-specific PCRs for the investigation of the most common subtypes of Blastocystis (ST1 to ST4) to a healthy human cohort (n = 50). We detected mixed infections in 22% of the cases, all of which had been identified as single-ST infections in a previous study using state-of-the-art methods. Our results show that certain STs occur predominantly as either single (ST3 and 4) or mixed (ST1) infections, which may reflect inter alia transient colonization patterns and/or cooperative or competitive interactions between different STs. Comparative analyses with other primers that have been used extensively for ST-specific analysis found them unsuitable for detection of mixed- and, in some cases, single-ST infections. Collectively, our data shed new light on the diversity of Blastocystis within and between human hosts. Moreover, the development of these PCR assays will facilitate future work on the molecular epidemiology and significance of mixed infections in groups of interest, including health and disease cohorts, and also help identify sources of Blastocystis transmission to humans, including identifying potential animal and environmental reservoirs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates

    Directory of Open Access Journals (Sweden)

    Hermans Peter WM

    2011-01-01

    Full Text Available Abstract Background M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM and exacerbations of chronic obstructive pulmonary disease (COPD. With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed. Results The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH, which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement. Conclusions M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens.

  9. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers.

    Science.gov (United States)

    Kabeerdoss, Jayakanthan; Devi, R Shobana; Mary, R Regina; Prabhavathi, D; Vidya, R; Mechenro, John; Mahendri, N V; Pugazhendhi, Srinivasan; Ramakrishna, Balakrishnan S

    2011-12-23

    Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet. 26 women aged 18-21 (median 19) years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing Bifidobacterium lactis Bb12® (10⁹ in 200 ml) for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184) and returned to normal after cessation of probiotic yoghurt intake. Bifidobacterium lactis Bb12® increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.

  10. Stratification of the phase clouds and statistical effects of the non-Markovity in chaotic time series of human gait for healthy people and Parkinson patients

    Science.gov (United States)

    Yulmetyev, Renat; Demin, Sergey; Emelyanova, Natalya; Gafarov, Fail; Hänggi, Peter

    2003-03-01

    In this work we develop a new method of diagnosing the nervous system diseases and a new approach in studying human gait dynamics with the help of the theory of discrete non-Markov random processes (Phys. Rev. E 62 (5) (2000) 6178, Phys. Rev. E 64 (2001) 066132, Phys. Rev. E 65 (2002) 046107, Physica A 303 (2002) 427). The stratification of the phase clouds and the statistical non-Markov effects in the time series of the dynamics of human gait are considered. We carried out the comparative analysis of the data of four age groups of healthy people: children (from 3 to 10 year olds), teenagers (from 11 to 14 year olds), young people (from 21 up to 29 year olds), elderly persons (from 71 to 77 year olds) and Parkinson patients. The full data set are analyzed with the help of the phase portraits of the four dynamic variables, the power spectra of the initial time correlation function and the memory functions of junior orders, the three first points in the spectra of the statistical non-Markov parameter. The received results allow to define the predisposition of the probationers to deflections in the central nervous system caused by Parkinson's disease. We have found out distinct differences between the five submitted groups. On this basis we offer a new method of diagnostics and forecasting Parkinson's disease.

  11. Effects of an antisense oligonucleotide inhibitor of C-reactive protein synthesis on the endotoxin challenge response in healthy human male volunteers.

    Science.gov (United States)

    Noveck, Robert; Stroes, Erik S G; Flaim, JoAnn D; Baker, Brenda F; Hughes, Steve; Graham, Mark J; Crooke, Rosanne M; Ridker, Paul M

    2014-07-10

    C-reactive protein (CRP) binds to damaged cells, activates the classical complement pathway, is elevated in multiple inflammatory conditions, and provides prognostic information on risk of future atherosclerotic events. It is controversial, however, as to whether inhibiting CRP synthesis would have any direct anti-inflammatory effects in humans. A placebo-controlled study was used to evaluate the effects of ISIS 329993 (ISIS-CRPR x) on the acute-phase response after endotoxin challenge in 30 evaluable subjects. Healthy adult males were randomly allocated to receive 6 injections over a 22-day period of placebo or active therapy with ISIS 329993 at 400- or 600-mg doses. Eligible subjects were subsequently challenged with a bolus of endotoxin (2 ng/kg). Inflammatory and hematological biomarkers were measured before and serially after the challenge. ISIS-CRPR x was well tolerated with no serious adverse events. Median CRP levels increased more than 50-fold from baseline 24 hours after endotoxin challenge in the placebo group. In contrast, the median increase in CRP levels was attenuated by 37% (400 mg) and 69% (600 mg) in subjects pretreated with ISIS-CRPR x (Pantisense oligonucleotides and provide an investigative tool to further define the role of CRP in human pathological conditions. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  12. SPE-UPLC-MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women$

    Institute of Scientific and Technical Information of China (English)

    Pravin G. Vanol; Puran Singhal; Priyanka A. Shah; Jaivik V. Shah; Pranav S. Shrivastav; Mallika Sanyal

    2016-01-01

    A rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method is described for determination of letrozole in human plasma. Following solid phase ex-traction (SPE) of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was per-formed on Acquity UPLC BEH C18 (50 mm ? 2.1 mm, 1.7 mm) column using methanol-0.1%formic acid in water (85:15, v/v) as the mobile phase. Detection was carried out on a triple quadrupole mass spec-trometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM) following the transitions at m/z 286.2-217.0 and m/z 290.2-221.0, respectively. The calibration plots were linear through the con-centration range of 0.10–100 ng/mL (r2Z0.9990) using 100 mL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was r 5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR) of 74 subject samples.

  13. Stratification of the phase clouds and statistical effects of the non-Markovity in chaotic time series of human gait for healthy people and Parkinson patients

    CERN Document Server

    Yulmetyev, R M; Emelyanova, N; Gafarov, F; Hänggi, P; Yulmetyev, Renat; Demin, Sergey; Emelyanova, Natalya; Gafarov, Fail; Hanggi, Peter

    2003-01-01

    In this work we develop a new method of diagnosing the nervous system diseases and a new approach in studying human gait dynamics with the help of the theory of discrete non-Markov random processes. The stratification of the phase clouds and the statistical non-Markov effects in the time series of the dynamics of human gait are considered. We carried out the comparative analysis of the data of four age groups of healthy people: children (from 3 to 10 year olds), teenagers (from 11 to 14 year oulds), young people (from 21 up to 29 year oulds), elderly persons (from 71 to 77 year olds) and Parkinson patients. The full data set are analyzed with the help of the phase portraits of the four dynamic variables, the power spectra of the initial time correlation function and the memory functions of junior orders, the three first points in the spectra of the statistical non-Markov parameter. The received results allow to define the predisposition of the probationers to deflections in the central nervous system caused b...

  14. Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival.

    Science.gov (United States)

    Perrotta, Ida; Perri, Mariarita; Santoro, Marta; Panza, Salvatore; Caroleo, Maria C; Guido, Carmela; Mete, Annamaria; Cione, Erika; Aquila, Saveria

    2015-01-01

    Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.

  15. Impact of Gluten-Friendly Bread on the Metabolism and Function of In Vitro Gut Microbiota in Healthy Human and Coeliac Subjects

    Science.gov (United States)

    Bevilacqua, Antonio; Costabile, Adele; Bergillos-Meca, Triana; Gonzalez, Isidro; Landriscina, Loretta; Ciuffreda, Emanuela; D’Agnello, Paola; Corbo, Maria Rosaria; Sinigaglia, Milena; Lamacchia, Carmela

    2016-01-01

    The main aim of this paper was to assess the in vitro response of healthy and coeliac human faecal microbiota to gluten-friendly bread (GFB). Thus, GFB and control bread (CB) were fermented with faecal microbiota in pH-controlled batch cultures. The effects on the major groups of microbiota were monitored over 48 h incubations by fluorescence in situ hybridisation. Short-chain fatty acids (SCFAs) were measured by high-performance liquid chromatography (HPLC). Furthermore, the death kinetics of Lactobacillus acidophilus, Bifidobacterium animalis subsp. lactis, Staphylococcus aureus, and Salmonella Typhimurium in a saline solution supplemented with GFB or CB were also assessed. The experiments in saline solution pinpointed that GFB prolonged the survival of L. acidophilus and exerted an antibacterial effect towards S. aureus and S. Typhimurium. Moreover, GFB modulated the intestinal microbiota in vitro, promoting changes in lactobacilli and bifidobacteria members in coeliac subjects. A final multivariate approach combining both viable counts and metabolites suggested that GFB could beneficially modulate the coeliac gut microbiome; however, human studies are needed to prove its efficacy. PMID:27632361

  16. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    Kabeerdoss Jayakanthan

    2011-12-01

    Full Text Available Abstract Background Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet. Findings 26 women aged 18-21 (median 19 years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing Bifidobacterium lactis Bb12® (109 in 200 ml for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184 and returned to normal after cessation of probiotic yoghurt intake. Conclusions Bifidobacterium lactis Bb12® increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.

  17. 3D spatially encoded and accelerated TE-averaged echo planar spectroscopic imaging in healthy human brain.

    Science.gov (United States)

    Iqbal, Zohaib; Wilson, Neil E; Thomas, M Albert

    2016-03-01

    Several different pathologies, including many neurodegenerative disorders, affect the energy metabolism of the brain. Glutamate, a neurotransmitter in the brain, can be used as a biomarker to monitor these metabolic processes. One method that is capable of quantifying glutamate concentration reliably in several regions of the brain is TE-averaged (1) H spectroscopic imaging. However, this type of method requires the acquisition of multiple TE lines, resulting in long scan durations. The goal of this experiment was to use non-uniform sampling, compressed sensing reconstruction and an echo planar readout gradient to reduce the scan time by a factor of eight to acquire TE-averaged spectra in three spatial dimensions. Simulation of glutamate and glutamine showed that the 2.2-2.4 ppm spectral region contained 95% glutamate signal using the TE-averaged method. Peak integration of this spectral range and home-developed, prior-knowledge-based fitting were used for quantitation. Gray matter brain phantom measurements were acquired on a Siemens 3 T Trio scanner. Non-uniform sampling was applied retrospectively to these phantom measurements and quantitative results of glutamate with respect to creatine 3.0 (Glu/Cr) ratios showed a coefficient of variance of 16% for peak integration and 9% for peak fitting using eight-fold acceleration. In vivo scans of the human brain were acquired as well and five different brain regions were quantified using the prior-knowledge-based algorithm. Glu/Cr ratios from these regions agreed with previously reported results in the literature. The method described here, called accelerated TE-averaged echo planar spectroscopic imaging (TEA-EPSI), is a significant methodological advancement and may be a useful tool for categorizing glutamate changes in pathologies where affected brain regions are not known a priori. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Photodynamic activities of silicon phthalocyanines against achromic M6 melanoma cells and healthy human melanocytes and keratinocytes.

    Science.gov (United States)

    Decreau, R; Richard, M J; Verrando, P; Chanon, M; Julliard, M

    1999-01-01

    Dichlorosilicon phthalocyanine (Cl2SiPc) and bis(tri-n-hexylsiloxy) silicon phthalocyanine (HexSiPc) have been evaluated in vitro as potential photosensitizers for photodynamic therapy (PDT) against the human amelanotic melanoma cell line M6. Each photosensitizer is dissolved in a solvent-PBS mixture, or entrapped in egg-yolk lecithin liposomes or in Cremophor EL micelles. The cells are incubated for 1 h with the sensitizer and then irradiated for 20 min, 1 h or 2 h (lambda > 480 nm, 10 mW cm-2). The photocytotoxic effect is dependent on the photosensitizer concentration and the light dose. Higher phototoxicity is observed after an irradiation of 2 h: treatment with a solution of photosensitizer (2 x 10(-9) M) leads to 10% (HexSiPc in egg-yolk lecithin liposomes) or 20% (Cl2SiPc in DMF-PBS solution) cell viability. After 1 h incubation and 20 min of light exposure, the photodynamic effect is connected with the type of delivery system used. For HexSiPc, lower cell viability is found when this photosensitizer is entrapped in egg-yolk lecithin instead of solvent-PBS or for Cremophor EL micelles with Cl2SiPc. Liposome-delivered HexSiPc leads to lipid damage in M6 cells, illustrated by an increase of thiobarbituric acid-reacting substances (TBARs), but the change is not significant with Cremophor EL. The same is observed for the antioxidative defences after photodynamic stress. The cells irradiated with HexSiPc entrapped in liposomes display an increase of superoxide dismutase (SOD) activity and a decrease of glutathione (GSH) level, glutathione peroxidase (GSHPx) and catalase (Cat) activities.

  19. Radiation-induced bystander effect in healthy G{sub 0} human lymphocytes: Biological and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Belloni, Paola; Latini, Paolo [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo De Lellis, I-01100 Viterbo (Italy); Palitti, Fabrizio, E-mail: palitti@unitus.it [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo De Lellis, I-01100 Viterbo (Italy)

    2011-08-01

    To study the bystander effects, G{sub 0} human peripheral blood lymphocytes were X-irradiated with 0.1, 0.5 and 3 Gy. After 24 h, cell-free conditioned media from irradiated cultures were transferred to unexposed lymphocytes. Following 48 h of medium transfer, viability, induction of apoptosis, telomere shortening, reactive oxygen species (ROS) levels and micronuclei (after stimulation) were analyzed. A statistically significant decrement in cell viability, concomitant with the loss of mitochondrial membrane potential, telomere shortening, increases in hydrogen peroxide (H{sub 2}O{sub 2}) and superoxide anion (O{sub 2}{sup -}) with depletion of intracellular glutathione (GSH) level, and higher frequencies of micronuclei, were observed in bystander lymphocytes incubated with medium from 0.5 and 3 Gy irradiated samples, compared to lymphocytes unexposed. Furthermore, no statistically significant difference between the response to 0.5 and 3 Gy of irradiation in bystander lymphocytes, was found. However, when lymphocytes were irradiated with 0.1 Gy, no bystander effect with regard to viability, apoptosis, telomere length, and micronuclei was observed, although a high production of ROS level persisted. Radiation in the presence of the radical scavenger dimethyl sulfoxide (DMSO) suppressed oxidative stress induced by 3 Gy of X-rays with the effective elimination of bystander effects, suggesting a correlation between ROS and bystander signal formation in irradiated cells. The data propose that bystander effect might be mostly due to the reactions of radiation induced free radicals on DNA, with the existence of a threshold at which the bystander signal is not operative (0.1 Gy dose of X-rays). Our results may have clinical implications for health risk associated with radiation exposure.

  20. Influence of aripiprazole, risperidone, and amisulpride on sensory and sensorimotor gating in healthy 'low and high gating' humans and relation to psychometry.

    Science.gov (United States)

    Csomor, Philipp A; Preller, Katrin H; Geyer, Mark A; Studerus, Erich; Huber, Theodor; Vollenweider, Franz X

    2014-09-01

    Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled, within-subject design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50 suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50 suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50 suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters, whereas modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50 suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50 suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase II/III development plans by providing additional information for critical decision making.

  1. Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study

    Directory of Open Access Journals (Sweden)

    Klautau-Guimarães Maria N

    2010-05-01

    Full Text Available Abstract Background Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events. Methods We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala, catalase (CAT -21A/T, glutathione peroxidase 1 (GPx-1 Pro198Leu, ACE (I/D and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135 to hydrogen peroxide (H2O2, and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H2O2 at 250 μM and 1 mM. Results After treatment with H2O2 at 250 μM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress. Conclusions The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.

  2. Nutrient Contents per Serving of Twelve Varieties of Cooked Rice Marketed in Jordan

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    Jafar M. El-Qudah

    2008-01-01

    Full Text Available Jordan imports rice from different countries without any quality preferences. Twelve varieties of cooked rice marketed in Jordan were analyzed. The content per serving of these varieties were computed for energy, protein, carbohydrates, fat, calcium, sodium, potassium, magnesium, manganese, copper, iron and phosphorous. The protein content per serving found to range from 0.49 g for La Cigala rice to 6.2 g for Harvest rice. The fat content for all rice brands was less than 0.37 g per serving. The energy content ranged from 172.12 g/serving for Basmati rice to 212.25 g/serving for Sun White rice. Generally, all rice varieties contain significant amounts of minerals per serving. Ruzzana found to contain the highest level of calcium (38.2 mg/serving and Amber the lowest calcium content (6.7 mg/serving. Magnesium content found to range from 5.7 mg/serving for Royal Umberella rice to 16.3 mg/serving for Ruzzana rice. Consumption of one serving of Harvest cooked rice will cover 13.5% of the daily requirement of protein for females and 11.1% for males. Manganese content of one serving of Harvest, Sun White, Abu bent and La Cigala will cover 22.2% of the daily requirements for females and 14.7% for males, while consumption of one of Basmati, Sos rice or Amber will cover only 11.1% and 8.75 of requirement for females and males respectively. Planning a healthful diet is not a simple task. Dietary Reference Intake planning and assessing the diets of individuals or groups of healthy individuals according to their stage of life and sex. Food choice is a function of many factors, including personal preferences, habits, ethnic heritage and tradition. Dietary guidelines for Americans, consider whole grain products like rice are among the food groups that form the basis of a healthy diet. Including rice as part of a healthy, balanced diet can be linked to overall healthier eating patterns. Rice eaters are more likely to eat a diet consistent with the 2005 Dietary

  3. White Grape Juice Elicits a Lower Breath Hydrogen Response Compared with Apple Juice in Healthy Human Subjects: A Randomized Controlled Trial.

    Science.gov (United States)

    Erickson, Jennifer; Wang, Qi; Slavin, Joanne

    2017-06-01

    Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS) are used to manage symptoms in individuals with irritable bowel syndrome. Although effective at reducing symptoms, the diet can be complex and restrictive. In addition, there are still large gaps in the literature and many foods with unclear effects in the gastrointestinal (GI) tract, like fruit juice. Although many fruits are allowable on a low-FODMAP diet, consumption of all fruit juice is generally cautioned due to the large fructose load contained in juice, regardless of the glucose concentration. Very little research exists regarding the importance of limiting fructose load during a low-FODMAP diet; therefore, individuals following a low-FODMAP diet may be unnecessarily restricting their diets. To determine whether there is a difference in GI tolerance between juice from a high-FODMAP fruit (apple juice) and juice from a low-FODMAP fruit (white grape juice) in healthy human subjects. The goal is to provide insight into the role of juice in a low-FODMAP diet. A double-blind, randomized, controlled crossover study was conducted with 40 healthy adults. Fasted subjects consumed 12 oz of either apple juice or white grape juice. Breath hydrogen measures were taken at baseline, 1, 2, and 3 hours. Subjective GI tolerance surveys were completed at the same time intervals and at 12 and 24 hours. Breath hydrogen and GI symptoms were assessed with area under the curve analysis. Significance was determined with a two-sided t test with a P value juice resulted in a greater mean breath hydrogen area under the curve at 23.3 ppm/hour (95% CI 13.0 to 33.6) compared with white grape juice at 5.8 ppm/hour (95% CI -4.6 to 16.1) (Pjuices were well tolerated and neither produced any severe symptoms in healthy adults. White grape juice consumption resulted in only a small rise in breath hydrogen, which may suggest excluding foods only because of the high fructose load could be

  4. No Effects of Acute Exposure to Wi-Fi Elect