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Sample records for pharmacologic concentrations selectively

  1. Preparation of selective molybdenum concentrate from collective coppermolybdenum concentrate

    Directory of Open Access Journals (Sweden)

    N. Tusupbaev

    2016-06-01

    Full Text Available The paper considers possibilities of selective separation of the concentrate of copper and molybdenum from a collective copper-molybdenum concentrate of Aktogay deposit using regrinding and conventional flotation reagents. In the case of conventional flotoreagents, the content of molybdenum in a molybdenum concentrate was 8.0% at extraction effectiveness 83.12%. At 27.96% extraction degree of copper, it’s content in the concentrate equaled to 21.3%. After regrinding, molybdenum content in the concentrate was 24.0% at the extraction effectiveness 59.63%, and copper content in the concentrate was 21.9% at the recovery of 61.23%. Thus, the regrinding of a collective copper-molybdenum concentrate resulted in an increase in the content of molybdenum in molybdenum concentrate by 16%, and the copper concentration increased by 0.6%.

  2. [The receptorial responsiveness method (RRM): a new possibility to estimate the concentration of pharmacologic agonists at their receptors].

    Science.gov (United States)

    Pák, Krisztián; Kiss, Zsuzsanna; Erdei, Tamás; Képes, Zita; Gesztelyi, Rudolf

    2014-01-01

    Cardiovascular disease is the biggest challenge in terms of life expectancy in developed countries. Adenosine contributes to the adaptation of the heart to ischemia and hypoxia, because adenosine, in addition to its metabolite role in the nucleic acid metabolism, is the endogenous agonist of the ubiquitous adenosine receptor family. Adenosine receptor activation is beneficial in most cases, it improves the balance between energy supply and consumption, reduces injury caused by stressors and inhibits the unfavorable tissue remodeling. Pharmacological manipulation of cardioprotective effects evoked by adenosine is an important, although to date not sufficiently utilized endeavor that may have therapeutic and preventive implications in cardiovascular diseases. As the ligand binding site of adenosine receptors is accessible from the extracellular space, it is especially important to know the adenosine concentration of the interstitial fluid ([Ado](ISF)). However, in the functioning heart, [Ado](ISF) values range in an extremely wide interval, spanning from nano- to micromolar concentrations, as estimated by the commonly used methods. Our recently developed procedure, the receptorial responsiveness method (RRM), may resolve this problem in certain cases. RRM enables quantification of an acute increase in the concentration of a pharmacological agonist, uniquely in the microenvironment of the receptors of the given agonist. As a limitation, concentration of agonists with short half-life (just like adenosine) at their receptors can only be quantified with the equieffective concentration of a stable agonist exerting the same action. In a previous study using RRM, inhibition of the transmembrane nucleoside transport in the euthyroid guinea pig atrium produced an increase in [Ado](ISF) that was equieffective with 18.8 +/- 3 nM CPA (N6-cyclopentyladenosine, a stable, selective A1 adenosine receptor agonist). This finding is consistent with observations of others, i.e., in the

  3. Ketoconazole inhibits the cellular uptake of anandamide via inhibition of FAAH at pharmacologically relevant concentrations.

    Directory of Open Access Journals (Sweden)

    Emmelie Björklund

    Full Text Available The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA.The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 µM, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component of 34 µM.The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer.

  4. Pharmacologic perspectives of functional selectivity by the angiotensin II type 1 receptor

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Hansen, Jakob Lerche

    2008-01-01

    and to sudden injury occurring in the circulatory system. Hence, current drugs that block all AT(1) receptor actions most likely leave room for improvement. Recent developments show that two major signaling pathways used by the AT(1) receptor may be dissected by pharmacologic means. Key pathologic responses...... protein actions and simultaneous activation of G protein-dependent or -independent signaling could therefore be desirable in certain situations. The previously unappreciated concept of "functional selectivity" makes this exact strategy feasible and may yield improved drugs for cardiovascular therapy....

  5. SVM Based Descriptor Selection and Classification of Neurodegenerative Disease Drugs for Pharmacological Modeling.

    Science.gov (United States)

    Shahid, Mohammad; Shahzad Cheema, Muhammad; Klenner, Alexander; Younesi, Erfan; Hofmann-Apitius, Martin

    2013-03-01

    Systems pharmacological modeling of drug mode of action for the next generation of multitarget drugs may open new routes for drug design and discovery. Computational methods are widely used in this context amongst which support vector machines (SVM) have proven successful in addressing the challenge of classifying drugs with similar features. We have applied a variety of such SVM-based approaches, namely SVM-based recursive feature elimination (SVM-RFE). We use the approach to predict the pharmacological properties of drugs widely used against complex neurodegenerative disorders (NDD) and to build an in-silico computational model for the binary classification of NDD drugs from other drugs. Application of an SVM-RFE model to a set of drugs successfully classified NDD drugs from non-NDD drugs and resulted in overall accuracy of ∼80 % with 10 fold cross validation using 40 top ranked molecular descriptors selected out of total 314 descriptors. Moreover, SVM-RFE method outperformed linear discriminant analysis (LDA) based feature selection and classification. The model reduced the multidimensional descriptors space of drugs dramatically and predicted NDD drugs with high accuracy, while avoiding over fitting. Based on these results, NDD-specific focused libraries of drug-like compounds can be designed and existing NDD-specific drugs can be characterized by a well-characterized set of molecular descriptors. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents with diverse selectivity profiles towards metabotropic and ionotropic glutamate receptor subtypes

    DEFF Research Database (Denmark)

    Madsen, Ulf; Pickering, Darryl S; Nielsen, Birgitte

    2005-01-01

    4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies...

  7. Efficient Generation and Selection of Virtual Populations in Quantitative Systems Pharmacology Models.

    Science.gov (United States)

    Allen, R J; Rieger, T R; Musante, C J

    2016-03-01

    Quantitative systems pharmacology models mechanistically describe a biological system and the effect of drug treatment on system behavior. Because these models rarely are identifiable from the available data, the uncertainty in physiological parameters may be sampled to create alternative parameterizations of the model, sometimes termed "virtual patients." In order to reproduce the statistics of a clinical population, virtual patients are often weighted to form a virtual population that reflects the baseline characteristics of the clinical cohort. Here we introduce a novel technique to efficiently generate virtual patients and, from this ensemble, demonstrate how to select a virtual population that matches the observed data without the need for weighting. This approach improves confidence in model predictions by mitigating the risk that spurious virtual patients become overrepresented in virtual populations.

  8. Selection of antibiotic resistance at very low antibiotic concentrations.

    Science.gov (United States)

    Sandegren, Linus

    2014-05-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  9. Stereochemistry and molecular pharmacology of (S)-thio-ATPA, a new potent and selective GluR5 agonist

    DEFF Research Database (Denmark)

    Stensbøl, T B; Jensen, H S; Nielsen, B

    2001-01-01

    )-Glu) receptors (EC(50)=14 microM), comparable in potency with ATPA (EC(50)=34 microM). Recent findings, that (S)-ATPA is a potent (EC(50)=0.48 microM) and selective agonist at homomerically expressed ionotropic GluR5, prompted us to resolve thio-ATPA using chiral chromatography and pharmacologically characterize...

  10. Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator.

    Science.gov (United States)

    Zhang, Xuqing; Allan, George F; Tannenbaum, Pamela; Sbriscia, Tifanie; Linton, Olivia; Lai, Muh-Tsann; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Lundeen, Scott G; Sui, Zhihua

    2013-03-01

    Selective androgen receptor modulators (SARMs) are androgens with tissue-selective activity. SARMs that have anabolic activity on muscle while having minimal stimulatory activity on prostate are classified as SARM agonists. They can be used to prevent the loss of lean body mass that is associated with cancer, immunodeficiency, renal disease and aging. They may also have anabolic activity on bone; thus, unlike estrogens, they may reverse the loss of bone strength associated with aging or hypogonadism. Our in-house effort on SARM program discovers a nonsteroidal androgen receptor ligand with a unique imidazolopyrazole moiety in its structure. In vitro, this compound is a weak androgen receptor binder and a weak androgen agonist. Despite this, in orchidectomized mature rats it is an effective SARM agonist, with an ED(50) on levator ani muscle of 3.3mg/kg and an ED(50) on ventral prostate of >30mg/kg. It has its maximal effect on muscle at the dose of 10mg/kg. In addition, this compound has mixed agonistic and antagonistic activities on prostate, reducing the weight of that tissue in intact rats by 22% at 10mg/kg. The compound does not have significant effect on gonadotropin levels or testosterone levels in both orchidectomized and intact male rats. It does not have notable progestin, estrogen or glucocorticoid agonistic or antagonistic activity in rats. In a female sexual behavior model, it improves the sexual desire of ovariectomized female rats for sexually mature intact males over nonsexually ovariectomized females. Overall, the imidazolopyrazole is a potent prostate-sparing candidate for development as a SARM agonist with an appropriate pharmacological profile for clinical benefit in muscle-wasting conditions and female sexual function disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Selection of antibiotic resistance at very low antibiotic concentrations

    OpenAIRE

    Sandegren, Linus

    2014-01-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are fou...

  12. Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist.

    Science.gov (United States)

    Arai, Kiyoshi; Homma, Tsuyoshi; Morikawa, Yuka; Ubukata, Naoko; Tsuruoka, Hiyoyuki; Aoki, Kazumasa; Ishikawa, Hirokazu; Mizuno, Makoto; Sada, Toshio

    2015-08-15

    The present study was designed to characterize the pharmacological profile of CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist. In the radioligand-binding assay, CS-3150 inhibited (3)H-aldosterone binding to mineralocorticoid receptor with an IC50 value of 9.4nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 36 and 713nM, respectively. CS-3150 also showed at least 1000-fold higher selectivity for mineralocorticoid receptor over other steroid hormone receptors, glucocorticoid receptor, androgen receptor and progesterone receptor. In the reporter gene assay, CS-3150 inhibited aldosterone-induced transcriptional activation of human mineralocorticoid receptor with an IC50 value of 3.7nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 66 and 970nM, respectively. CS-3150 had no agonistic effect on mineralocorticoid receptor and did not show any antagonistic or agonistic effect on glucocorticoid receptor, androgen receptor and progesterone receptor even at the high concentration of 5μM. In adrenalectomized rats, single oral administration of CS-3150 suppressed aldosterone-induced decrease in urinary Na(+)/K(+) ratio, an index of in vivo mineralocorticoid receptor activation, and this suppressive effect was more potent and longer-lasting than that of spironolactone and eplerenone. Chronic treatment with CS-3150 inhibited blood pressure elevation induced by deoxycorticosterone acetate (DOCA)/salt-loading to rats, and this antihypertensive effect was more potent than that of spironolactone and eplerenone. These findings indicate that CS-3150 is a selective and highly potent mineralocorticoid receptor antagonist with long-lasting oral activity. This agent could be useful for the treatment of hypertension, cardiovascular and renal disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Concentration reduction of selected pollutants in fish culture ...

    African Journals Online (AJOL)

    Concentration reduction of selected pollutants in fish culture effluents using plastic straws and palm kernel shells. ... Journal of Environmental Extension ... Their effluent treatment ability were evaluated in terms of reduction made to ...

  14. Effects of pharmacological concentrations of dietary zinc oxide on growth of post-weaning pigs: a meta-analysis.

    Science.gov (United States)

    Sales, James

    2013-06-01

    Pharmacological dietary zinc (Zn) concentrations of 1,000 to 3,000 mg/kg diet from Zn oxide have been found to increase growth in post-weaning pigs. However, results were inconsistent among studies. A frequentist meta-analysis, in which effects were numerically described with standardized effect sizes (Hedges's g), was conducted in order to identify and quantify the responses in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G/F) in post-weaning pigs upon dietary Zn supplementation from Zn oxide. The inability of independent continuous variables to explain significant heterogeneity obtained with fixed effect models necessitated the use of random effects models to calculate summary statistics. Dietary Zn supplementation increased (P potential environmental pollution will have to be negated by alternative feed additives and management strategies in order to prevent economic losses.

  15. [Ion channels that are sensitive to the extracellular concentration of protons: their structure, function, pharmacology and pathophysiology].

    Science.gov (United States)

    Mercado, F; Vega, R; Soto, E

    Acid sensing ion channels (ASIC) members of the ENaC degenerine channel family, have been shown to participate in various sensorial pathways including nociception, also they have been shown to participate in synaptic transmission, learning and memory processes and in the physiopathology of the ischemic stroke. The proton concentration in the organism is strictly regulated by distinct buffer systems. Drastic changes of pH are generated only by pathological conditions as is the ischemia; however, some physiological processes may produce local changes in the extracellular pH. Recently, a new family of proton receptors known as ASIC has been cloned. These are ionic channels inactivated at physiological pH (7.4) and activated with a pH fall (increase in H+ concentration). ASICs are permeable to sodium ions and in a lesser degree to calcium ions, activation of these channels leads to an increase in cell excitability. The ASICs are distributed widely in the central and peripheral nervous system, and in specialized epithelia. In the past few years they have become a focus of interest due to its role in nociception, taste perception, long term potentation and the physiopathology of ischemic stroke. In this review we address the most relevant molecular, physiological and pharmacological aspects of the ASICs, its participation in some pathological process, and the perspectives of basic and clinic investigation in this arising research field.

  16. A selective review of glutamate pharmacological therapy in obsessive–compulsive and related disorders

    OpenAIRE

    Grados, Marco; Atkins,Elizabeth; Kovacikova,Gabriela Ika; McVicar,Erin

    2015-01-01

    Marco A Grados,1 Elizabeth B Atkins,2 Gabriela I Kovacikova,3 Erin McVicar4 1Division of Child and Adolescent Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Psychology, Smith College, Northampton, MA, 3Department of Psychology, Wellesley College, Wellesley, MA, 4Susquehanna University, Selinsgrove, PA, USA Abstract: Glutamate, an excitatory central nervous system neurotransmitter, is emerging as a potential alternative pharmacological treatment when co...

  17. Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models

    Czech Academy of Sciences Publication Activity Database

    Tavares, M. T.; Shen, S.; Knox, T.; Hadley, M.; Kutil, Zsofia; Bařinka, Cyril; Villagra, A.; Kozikowski, A. P.

    2017-01-01

    Roč. 8, č. 10 (2017), s. 1031-1036 ISSN 1948-5875 R&D Projects: GA ČR GA15-19640S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : HDAC6 inhibitors * nexturastat A * melanoma Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.746, year: 2016

  18. Organic wavelength selective mirrors for luminescent solar concentrators

    NARCIS (Netherlands)

    Verbunt, P.P.C.; Debije, M.G.; Broer, D.J.; Bastiaansen, C.W.M.; Boer, de D.K.G.; Wehrspohn, R.; Gombert, A.

    2012-01-01

    Organic polymeric chiral nematic liquid crystalline (cholesteric) wavelength selective mirrors can increase the efficiency of luminescent solar concentrators (LSCs) when they are illuminated with direct sunlight normal to the device. However, due to the angular dependence of the reflection band, at

  19. Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs

    DEFF Research Database (Denmark)

    Hudson, Brian D; Christiansen, Elisabeth; Tikhonova, Irina G

    2012-01-01

    When it is difficult to develop selective ligands within a family of related G-protein-coupled receptors (GPCRs), chemically engineered receptors activated solely by synthetic ligands (RASSLs) are useful alternatives for probing receptor function. In the present work, we explored whether a RASSL...... on this receptor and demonstrates that exploitation of pharmacological variation between species orthologs is a powerful method to generate novel chemically engineered GPCRs.-Hudson, B. D., Christiansen, E., Tikhonova, I. G., Grundmann, M., Kostenis, E., Adams, D. R., Ulven, T., Milligan, G. Chemically engineering...

  20. Pharmacological targeting of valosin containing protein (VCP) induces DNA damage and selectively kills canine lymphoma cells

    International Nuclear Information System (INIS)

    Nadeau, Marie-Ève; Rico, Charlène; Tsoi, Mayra; Vivancos, Mélanie; Filimon, Sabin; Paquet, Marilène; Boerboom, Derek

    2015-01-01

    Valosin containing protein (VCP) is a critical mediator of protein homeostasis and may represent a valuable therapeutic target for several forms of cancer. Overexpression of VCP occurs in many cancers, and often in a manner correlating with malignancy and poor outcome. Here, we analyzed VCP expression in canine lymphoma and assessed its potential as a therapeutic target for this disease. VCP expression in canine lymphomas was evaluated by immunoblotting and immunohistochemistry. The canine lymphoma cell lines CLBL-1, 17–71 and CL-1 were treated with the VCP inhibitor Eeyarestatin 1 (EER-1) at varying concentrations and times and were assessed for viability by trypan blue exclusion, apoptosis by TUNEL and caspase activity assays, and proliferation by propidium iodide incorporation and FACS. The mechanism of EER-1 action was determined by immunoblotting and immunofluorescence analyses of Lys48 ubiquitin and markers of ER stress (DDIT3), autophagy (SQSTM1, MAP1LC3A) and DNA damage (γH2AFX). TRP53/ATM-dependent signaling pathway activity was assessed by immunoblotting for TRP53 and phospho-TRP53 and real-time RT-PCR measurement of Cdkn1a mRNA. VCP expression levels in canine B cell lymphomas were found to increase with grade. EER-1 treatment killed canine lymphoma cells preferentially over control peripheral blood mononuclear cells. EER-1 treatment of CLBL-1 cells was found to both induce apoptosis and cell cycle arrest in G1. Unexpectedly, EER-1 did not appear to act either by inducing ER stress or inhibiting the aggresome-autophagy pathway. Rather, a rapid and dramatic increase in γH2AFX expression was noted, indicating that EER-1 may act by promoting DNA damage accumulation. Increased TRP53 phosphorylation and Cdkn1a mRNA levels indicated an activation of the TRP53/ATM DNA damage response pathway in response to EER-1, likely contributing to the induction of apoptosis and cell cycle arrest. These results correlate VCP expression with malignancy in canine B cell

  1. Analysis of Market Concentration in Selected Sectors of Public Procurement

    Directory of Open Access Journals (Sweden)

    Petr Svoboda

    2016-01-01

    Full Text Available The goal of this article is the analysis of influence of market concentration in selected areas of public procurement on chosen parameters of public procurement in years 2007 and 2011. Five concentration ratios and five parameters of contracts are calculated for each of five chosen areas of public tenders in 2007 and 2011. After this task, the correlation analysis between concentration ratios and parameters of contracts is done for finding out mutual relation between these two variables. Correlation analysis is then compared with four created hypotheses about the relationship between market concentration and parameters of public procurement The results of the analysis are surprising, because in most cases, the stated hypotheses were rejected, meaning that the correlations between the parameters of public procurement and market concentration were different than this study predicted based on economic theory. The possible reasons for this result, discussed in the article, are corruption and also poor quality of data from Information system of public procurement administered by the Ministry for Regional Development of Czech Republic.

  2. Concentrations of selected contaminants in cabin air of airbus aircrafts.

    Science.gov (United States)

    Dechow, M; Sohn, H; Steinhanses, J

    1997-07-01

    The concentrations of selected air quality parameters in aircraft cabins were investigated including particle numbers in cabin air compared to fresh air and recirculation air, the microbiological contamination and the concentration of volatile organic compounds (VOC). The Airbus types A310 of Swissair and A340 of Lufthansa were used for measurements. The particles were found to be mainly emitted by the passengers, especially by smokers. Depending on recirculation filter efficiency the recirculation air contained a lower or equal amount of particles compared to the fresh air, whereas the amount of bacteria exceeded reported concentrations within other indoor spaces. The detected species were mainly non-pathogenic, with droplet infection over short distances identified as the only health risk. The concentration of volatile organic compounds (VOC) were well below threshold values. Ethanol was identified as the compound with the highest amount in cabin air. Further organics were emitted by the passengers--as metabolic products or by smoking--and on ground as engine exhaust (bad airport air quality). Cleaning agents may be the source of further compounds.

  3. Testing of selected pharmacological agents for capturing waterfowl [Annual Progress Report

    Science.gov (United States)

    Cline, D.R.

    1970-01-01

    The response of game-farm mallards (Frost strain) to seven pharmacological immobilizing agents was evaluated in Phase I of a planned four-phase study. A limited amount of testing was also done with wild mallards. Single dosages were administered to determine the mean effective dose (ED50) and mean lethal dose (LD50), The therapeutic index, or safety factor (LD50/ED50), and palatability were also established. Optimum dosage rates of compounds administered orally on baits were not considered in this phase of the study. Compounds were-administered by intubation and calculated in terms of mg/kg. All except one compound produced narcosis within 5 minutes at the effective dose rate.Immobilization periods for the seven compounds ranged from 7-24 minutes, and recovery periods from 1.0-6.5 hours. Such wide variations in actions of the compounds can be attributed to a compound's rate of absorption, the ease with which it passes the blood-brain barrier, its solubility in tissues, and its rate of metabolism in the liver and kidneys. Length of both the immobilization and recovery periods were extended when dosages were increased. There was no delayed mortality among survivors with any of the seven compounds at either the ED50 or LD50. Females were generally more sensitive to the anesthetizing agents than males. The ED50 for wild mallards was substantially higher than that for the experimental game-farm birds for the two compounds on which this was tested.Tribromoethanol (Avertin of Winthrop Laboratories) satisfied all test criteria an Phase I and will be subjected to more intensive investigation in ensuing tests. Thiopental sodium (Pentothal of Amdal Company) and pentobarbital sodium (Nembutal of Abbott Laboratories) were judged to be marginal. Although their therapeutic indexes were good (5.00), recovery periods were prolonged and toxic convulsions occurred at medium to high dose rates as the LD50 was approached.Alpha-chloralose (Fisher Scientific) proved least promising of

  4. The Current State of Empirical Support for the Pharmacological Treatment of Selective Mutism

    Science.gov (United States)

    Carlson, John S.; Mitchell, Angela D.; Segool, Natasha

    2008-01-01

    This article reviews the current state of evidence for the psychopharmacological treatment of children diagnosed with selective mutism within the context of its link to social anxiety disorder. An increased focus on potential medication treatment for this disorder has resulted from significant monetary and resource limitations in typical practice,…

  5. Synthesis and Pharmacology of Halogenated δ-Opioid-Selective [D-Ala2]Deltorphin II Peptide Analogues

    Science.gov (United States)

    Pescatore, Robyn; Marrone, Gina F.; Sedberry, Seth; Vinton, Daniel; Finkelstein, Netanel; Katlowitz, Yitzchak E.; Pasternak, Gavril W.; Wilson, Krista R.; Majumdar, Susruta

    2015-01-01

    Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-D-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [D-Ala2]deltorphin II template, which is δ-selective in in vitro radioligand binding assays over the μ- and κ-opioid receptors. It is a full agonist in [35S]GTPγS functional assays and analgesic when administered supraspinally to mice. Analgesia of 3 (GATE3-8) is blocked by the selective δ receptor antagonist naltrindole, indicating that the analgesic action of 3 is mediated by the δ-opioid receptor. We have established a radioligand in which 125I isincorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese hamster ovary (CHO) cells expressing the δ receptor. Additionally, a series of peptides based on 3 (GATE3-8) was synthesized by incorporating various halogens in the para position on the aromatic ring of Phe3. The peptides were characterized for binding affinity at the μ-, δ-, and κ-opioid receptors, which showed a linear correlation between binding affinity and the size of the halogen substituent. These peptides may be interesting tools for probing δ-opioid receptor pharmacology. PMID:25844930

  6. Synthesis and pharmacology of halogenated δ-opioid-selective [d-Ala(2)]deltorphin II peptide analogues.

    Science.gov (United States)

    Pescatore, Robyn; Marrone, Gina F; Sedberry, Seth; Vinton, Daniel; Finkelstein, Netanel; Katlowitz, Yitzchak E; Pasternak, Gavril W; Wilson, Krista R; Majumdar, Susruta

    2015-06-17

    Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, which is δ-selective in in vitro radioligand binding assays over the μ- and κ-opioid receptors. It is a full agonist in [(35)S]GTPγS functional assays and analgesic when administered supraspinally to mice. Analgesia of 3 (GATE3-8) is blocked by the selective δ receptor antagonist naltrindole, indicating that the analgesic action of 3 is mediated by the δ-opioid receptor. We have established a radioligand in which (125)I is incorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese hamster ovary (CHO) cells expressing the δ receptor. Additionally, a series of peptides based on 3 (GATE3-8) was synthesized by incorporating various halogens in the para position on the aromatic ring of Phe(3). The peptides were characterized for binding affinity at the μ-, δ-, and κ-opioid receptors, which showed a linear correlation between binding affinity and the size of the halogen substituent. These peptides may be interesting tools for probing δ-opioid receptor pharmacology.

  7. Benzazepines: Structure-activity relationships between D1 receptor blockade and selected pharmacological effects

    International Nuclear Information System (INIS)

    Iorio, L.C.; Billiard, W.; Gold, E.H.

    1986-01-01

    This chapter describes the displacement of 3 H-23390 and 3 H-spiperone binding by dopamine agonists and antagonists. The authors undertook an evaluation of the ability of selected analogs of SCH 23390 to displace 3 H-SCH 23390 and 3 H-spiperone. Structure-activity relationships of SCH 23390 analogs: 7-position substituents, is shown. It is shown that, in general, benzazepines with a variety of substituents in the 7-position retain their selectivity for D 1 sites. Substituents at the 8-position and at the N-position are also discussed. The authors determine a correlation between displacement of 3 H-SCH 23390 and blockade of dopamine-sensitive adenylate cyclase (DSAC). These effects and inhibition of conditioned avoidance responsing (CAS) in rats was also studied. A detailed evaluation is presented of the effects of SCH 23390 and haloperidol in the Inclined Screen and CAR tests

  8. Changes in the levels of kynurenic acid and selected proinflammatory cytokines after pharmacological treatment and electroconvulsive therapy (ECT in patients with depressive disorder

    Directory of Open Access Journals (Sweden)

    Olajossy Marcin

    2016-06-01

    Full Text Available The aim of the present study was to compare the concentrations of KYNA, 3-OH-KYN and the cytokines TNF-α and IL-6 in patients with depression vs. healthy controls as well as in patients with depression treated pharmacologically vs. those treated using ECT. We also evaluated the relationship between the concentrations of KYNA, 3-OH-KYN and the cytokines TNF-α and IL-6 and clinical improvement measured on the MADRS scale in patients treated pharmacologically and those treated with ECT.

  9. Selective pharmacological modulation of renal peripheral-type benzodiazepine binding by treatment with diuretic drugs

    International Nuclear Information System (INIS)

    Lukeman, D.S.; Vaughn, D.A.; Fanestil, D.D.

    1988-01-01

    The authors have assessed the effects of in vivo administration of different classes of diuretic drugs on the expression of the peripheral-type benzodiazepine binding site (PBBS) in crude membranes derived from the cortex and outer medulla of rat kidney by saturation analysis with the PBBS-selective ligands [ 3 H]RO5-4864 and [ 3 H]PH 11195 in cortex and [ 3 H]RO5-4864 in outer medulla. Administration for 14-15 days of furosemide, a drug that blocks NaCl-KCl coupled transport in the thick ascending limb of the loop of Henle, produced a significant doubling in the PBBS density (B/sub max/) in outer medulla, a region of the kidney rich in thick ascending limbs, and produced a lesser but significant increase in PBBS density in the cortex. Conversely, administration for 14-15 days of the carbonic anhydrase inhibitor acetazolamide, which acts predominantly in the proximal tubule, and hydrochlorothiazide, which acts predominantly in the early distal tubule, elicited statistically significant increases in PBBS density in renal cortex but not in renal outer medulla. Furthermore, all drug treatments were without effect on the equilibrium dissociation constants (K/sub d/s) of [ 3 H]RO5-4864 and [ 3 H]PK 11195 binding to cortical and outer medullary membrane preparations. These findings demonstrate that the PBBS can be selectively up-regulated in different regions of the kidney by diuretic drugs with different modes/sites of action. 50 references, 1 table

  10. Pharmacology of JB-9315, a new selective histamine H2-receptor antagonist.

    Science.gov (United States)

    Palacios, B; Montero, M J; Sevilla, M A; San Román, L

    1998-02-01

    1. The histamine H2-receptor antagonistic activity and antisecretory and antiulcer effects of JB-9315 were studied in comparison with the standard H2 blocker ranitidine. 2. In vitro, JB-9315 is a competitive antagonist of histamine H2 receptors in the isolated, spontaneously beating guinea-pig right atrium, with a pA2 value of 7.30 relative to a value of 7.36 for ranitidine. JB-9315 was specific for the histamine H2 receptor because, at high concentration, it did not affect histamine- or acetylcholine-induced contractions in guinea-pig isolated ileum or rat isolated duodenum, respectively. 3. JB-9315 dose dependently inhibited histamine-, pentagastrin- or carbachol-stimulated acid secretion and basal secretion in the perfused stomach preparation of the anesthetized rat. In the pylorus-ligated rat after intraperitoneal administration, total acid output over 4 h was inhibited by JB-9315 with an ID50 of 32.8 mg/kg, confirming its H2-receptor antagonist properties. 4. JB-9315 showed antiulcer activity against cold stress plus indomethacin-induced lesions with an ID50 of 6.8 mg/kg. 5. JB-9315, 50 and 100 mg/kg, inhibited macroscopic gastric hemorrhagic lesions induced by ethanol. In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. 6. These results indicate that JB-9315 is a new antiulcer drug that exerts a cytoprotective effect in addition to its gastric antisecretory activity.

  11. Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

    Science.gov (United States)

    Jayant, Shalini; Sharma, Brij Mohan; Bansal, Rani; Sharma, Bhupesh

    2016-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The pharmacology of TD-8954, a potent and selective 5-HT4 receptor agonist with gastrointestinal prokinetic properties

    Directory of Open Access Journals (Sweden)

    David T Beattie

    2011-05-01

    Full Text Available This study evaluated the in vitro and in vivo pharmacological properties of TD-8954, a potent and selective 5-HT4 receptor agonist. TD-8954 had high affinity (pKi = 9.4 for human recombinant 5-HT4(c (h5-HT4(c receptors, and selectivity (> 2,000-fold over all other 5-HT receptors and non-5-HT receptors, ion channels, enzymes and transporters tested (n = 78. TD-8954 produced an elevation of cAMP in HEK-293 cells expressing the h5-HT4(c receptor (pEC50 = 9.3, and contracted the guinea pig colonic longitudinal muscle/myenteric plexus (LMMP preparation (pEC50 = 8.6. TD-8954 had moderate intrinsic activity (IA in the in vitro assays. In conscious guinea pigs, subcutaneous (s.c. administration of TD 8954 (0.03 - 3 mg/kg increased the colonic transit of carmine red dye, reducing the time taken for its excretion. Following intraduodenal (i.d. dosing to anesthetized rats, TD 8954 (0.03 - 10 mg/kg evoked a dose-dependent relaxation of the esophagus. Following oral administration to conscious dogs, TD 8954 (10 and 30 µg/kg produced an increase in contractility of the antrum, duodenum and jejunum. In a single ascending oral dose study in healthy human subjects, TD-8954 (0.1 - 20 mg increased bowel movement frequency and reduced the time to first stool. It is concluded that TD-8954 is a potent and selective 5-HT4 receptor agonist in vitro, with robust in vivo stimulatory activity in the gastrointestinal (GI tract of guinea pigs, rats, dogs and humans. TD-8954 may have clinical utility in patients with disorders of reduced GI motility.

  13. New selective and potent 5-HT1B/1D antagonists : Chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides

    NARCIS (Netherlands)

    Liao, Y; Bottcher, H; Harting, J; Greiner, H; van Amsterdam, C; Cremers, T; Sundell, S; Marz, J; Rautenberg, W; Wikstrom, H

    2000-01-01

    A series of new analogues of N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide (1; GR127935) as potent and selective 5-HT1B/1D antagonists were synthesized and evaluated pharmacologically. Their receptor binding profiles were comparable

  14. Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists at group I metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Madsen, U; Bräuner-Osborne, H; Frydenvang, Karla Andrea

    2001-01-01

    Using ibotenic acid (2) as a lead, two series of 3-isoxazolol amino acid ligands for (S)-glutamic acid (Glu, 1) receptors have been developed. Whereas analogues of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [AMPA, (RS)-3] interact selectively with ionotropic Glu receptors (i......GluRs), the few analogues of (RS)-2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid [HIBO, (RS)-4] so far known typically interact with iGluRs as well as metabotropic Glu receptors (mGluRs). We here report the synthesis and pharmacology of a series of 4-substituted analogues of HIBO. The hexyl analogue 9 was shown...... to originate in (S)-11 (EC(50) = 395 microM, K(b) = 86 and 90 microM, respectively). Compound 9, administered icv, but not sc, was shown to protect mice against convulsions induced by N-methyl-D-aspartic acid (NMDA). Compounds 9 and 11 were resolved using chiral HPLC, and the configurational assignments...

  15. Radionuclides and selected trace elements in marine protein concentrates

    Energy Technology Data Exchange (ETDEWEB)

    Beasley, T M; Jokela, T A; Eagle, R J

    1971-12-01

    The concentrations of various trace elements and radionuclides have been measured in marine protein concentrates prepared from surface feeding fishes. As with concentrates prepared from benthic fishes, the /sup 210/Pb-/sup 210/Po pair are the most significant radionuclides present. Concentrations of stable Pb, Co and Ag in certain concentrates are sufficiently high to contribute substantially to estimated current intakes of these elements.

  16. Comparison of combinatorial clustering methods on pharmacological data sets represented by machine learning-selected real molecular descriptors.

    Science.gov (United States)

    Rivera-Borroto, Oscar Miguel; Marrero-Ponce, Yovani; García-de la Vega, José Manuel; Grau-Ábalo, Ricardo del Corazón

    2011-12-27

    Cluster algorithms play an important role in diversity related tasks of modern chemoinformatics, with the widest applications being in pharmaceutical industry drug discovery programs. The performance of these grouping strategies depends on various factors such as molecular representation, mathematical method, algorithmical technique, and statistical distribution of data. For this reason, introduction and comparison of new methods are necessary in order to find the model that best fits the problem at hand. Earlier comparative studies report on Ward's algorithm using fingerprints for molecular description as generally superior in this field. However, problems still remain, i.e., other types of numerical descriptions have been little exploited, current descriptors selection strategy is trial and error-driven, and no previous comparative studies considering a broader domain of the combinatorial methods in grouping chemoinformatic data sets have been conducted. In this work, a comparison between combinatorial methods is performed,with five of them being novel in cheminformatics. The experiments are carried out using eight data sets that are well established and validated in the medical chemistry literature. Each drug data set was represented by real molecular descriptors selected by machine learning techniques, which are consistent with the neighborhood principle. Statistical analysis of the results demonstrates that pharmacological activities of the eight data sets can be modeled with a few of families with 2D and 3D molecular descriptors, avoiding classification problems associated with the presence of nonrelevant features. Three out of five of the proposed cluster algorithms show superior performance over most classical algorithms and are similar (or slightly superior in the most optimistic sense) to Ward's algorithm. The usefulness of these algorithms is also assessed in a comparative experiment to potent QSAR and machine learning classifiers, where they perform

  17. Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks

    DEFF Research Database (Denmark)

    Grady, Cheryl Lynn; Siebner, Hartwig R; Hornboll, Bettina

    2013-01-01

    Pharmacological manipulation of serotonin availability can alter the processing of facial expressions of emotion. Using a within-subject design, we measured the effect of serotonin on the brain's response to aversive face emotions with functional MRI while 20 participants judged the gender...... of neutral, fearful and angry faces. In three separate and counterbalanced sessions, participants received citalopram (CIT) to raise serotonin levels, underwent acute tryptophan depletion (ATD) to lower serotonin, or were studied without pharmacological challenge (Control). An analysis designed to identify...

  18. In vitro pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107.

    Science.gov (United States)

    Malysz, John; Anderson, David J; Grønlien, Jens H; Ji, Jianguo; Bunnelle, William H; Håkerud, Monika; Thorin-Hagene, Kirten; Ween, Hilde; Helfrich, Rosalind; Hu, Min; Gubbins, Earl; Gopalakrishnan, Sujatha; Puttfarcken, Pamela S; Briggs, Clark A; Li, Jinhe; Meyer, Michael D; Dyhring, Tino; Ahring, Philip K; Nielsen, Elsebet Ø; Peters, Dan; Timmermann, Daniel B; Gopalakrishnan, Murali

    2010-09-01

    cortical cultures against glutamate-induced toxicity. In summary, ABT-107 is a selective high affinity alpha7 nAChR agonist suitable for characterizing the roles of this subtype in pharmacological studies.

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

    African Journals Online (AJOL)

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

  20. Review of pump suction reducer selection: Eccentric or concentric reducers

    OpenAIRE

    Mahaffey, R M; van Vuuren, S J

    2014-01-01

    Eccentric reducers are traditionally recommended for the pump suction reducer fitting to allow for transportation of air through the fitting to the pump. The ability of a concentric reducer to provide an improved approach flow to the pump while still allowing air to be transported through the fitting is investigated. Computational fluid dynamics (CFD) were utilised to analyse six concentric and six eccentric reducer geometries at four different inlet velocities to determine the flow velocity ...

  1. Selected mineral and heavy metal concentrations in blood and ...

    African Journals Online (AJOL)

    Unknown

    Pb in the dead vultures were generally above values characteristic of heavy metal poisoning. ... of the food chain), may accumulate and concentrate heavy metals in their ..... µg/g wet weight) (Honda et al., 1990), which validates the order of ...

  2. Selected mineral and heavy metal concentrations in blood and ...

    African Journals Online (AJOL)

    Concentrations of eight essential elements (Ca, Co, Cr, Cu, Fe, Mn, Ni and Zn) and three toxic metals (Al, Pb and Sr) were measured in various tissue samples from African whitebacked (Pseudogyps africanus), Cape griffon (Gyps coprotheres) and Lappetfaced (Torgos tracheliotos) vultures in different regions of South ...

  3. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Department of Food Science and Technology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Zhu, Hong; Jia, Zhenquan [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Li, Jianrong [College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Misra, Hara P. [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Zhou, Kequan, E-mail: kzhou@wayne.edu [Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202 (United States); Li, Yunbo, E-mail: yli@vcom.vt.edu [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States)

    2009-12-04

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in {phi}X-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 {mu}M SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  4. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    International Nuclear Information System (INIS)

    Chen, Wei; Zhu, Hong; Jia, Zhenquan; Li, Jianrong; Misra, Hara P.; Zhou, Kequan; Li, Yunbo

    2009-01-01

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in φX-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 μM SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  5. Concentrating on beauty: sexual selection and sociospatial memory.

    Science.gov (United States)

    Becker, D Vaughn; Kenrick, Douglas T; Guerin, Stephen; Maner, Jon K

    2005-12-01

    In three experiments, location memory for faces was examined using a computer version of the matching game Concentration. Findings suggested that physical attractiveness led to more efficient matching for female faces but not for male faces. Study 3 revealed this interaction despite allowing participants to initially see, attend to, and match the attractive male faces in the first few turns. Analysis of matching errors suggested that, compared to other targets, attractive women were less confusable with one another. Results are discussed in terms of the different functions that attractiveness serves for men and women.

  6. GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

    Science.gov (United States)

    Busardò, Francesco P.; Jones, Alan W.

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  7. Anesthetic pharmacology

    National Research Council Canada - National Science Library

    Evers, Alex S; Maze, M; Kharasch, Evan D

    2011-01-01

    ...: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology...

  8. Heavy metal concentrations of selected public parks of Istanbul City

    Directory of Open Access Journals (Sweden)

    Demir Goksel

    2016-01-01

    Full Text Available Many cities, especially larger metropolises, parks are very important recreational areas where people usually have closer contact with flora. Therefore, the pollution level in the parks can have a greater effect on human health. Heavy metals are ubiquitous with the environment, as a result of both natural and anthropogenic activities, and humans are exposed to them through various pathways. Essentially, these areas are assumed to be less exposed to routine contaminants, but especially in metropolises, this assumption could prove false considering these areas are stuck within the confines of a city full of pollutant activity such as intense traffic. In this study; the relationships between heavy metal pollution levels (Cd, Cr, Cu, Ni, Pb, Zn and the pH and electrical conductivity (EC of soil samples were investigated from the parks on the Asian side of Istanbul. For this purpose, the most frequently visited 16 parks were selected as sampling sites. In the second part of the study, linear correlation is used for the data analysis.

  9. Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

    International Nuclear Information System (INIS)

    Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

    1989-01-01

    This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [ 3 H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

  10. Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

    DEFF Research Database (Denmark)

    Kromann, Hasse; Sløk, Frank A; Stensbøl, Tine B

    2002-01-01

    Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are bot...... antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs....

  11. A cell shrinkage-induced non-selective cation conductance with a novel pharmacology in Ehrlich-Lettre-ascites tumour cells

    DEFF Research Database (Denmark)

    Lawonn, Peter; Hoffmann, Else K; Hougaard, Charlotte

    2003-01-01

    In whole-cell recordings on Ehrlich-Lettre-ascites tumour (ELA) cells, the shrinkage-induced activation of a cation conductance with a selectivity ratio P(Na):P(Li):P(K):P(choline):P(NMDG) of 1.00:0.97:0.88:0.03:0.01 was observed. In order of potency, this conductance was blocked by Gd(3+)=benzam......-sensitive and -insensitive channels. In addition, because of its pharmacological profile, it may possibly be related to epithelial Na+ channels (ENaCs)....

  12. Pharmacologically relevant intake during chronic, free-choice drinking rhythms in selectively bred high alcohol-preferring mice.

    Science.gov (United States)

    Matson, Liana M; Grahame, Nicholas J

    2013-11-01

    Multiple lines of high alcohol-preferring (HAP) mice were selectively bred for their intake of 10% ethanol (v/v) during 24-hour daily access over a 4-week period, with the highest drinking lines exhibiting intakes in excess of 20 g/kg/day. We observed circadian drinking patterns and resulting blood ethanol concentrations (BECs) in the HAP lines. We also compared the drinking rhythms and corresponding BECs of the highest drinking HAP lines to those of the C57BL/6J (B6) inbred strain. Adult male and female crossed HAP (cHAP), HAP replicate lines 1, 2, 3 and B6 mice had free-choice access to 10% ethanol and water for 3 weeks prior to bi-hourly assessments of intake throughout the dark portion of the light-dark cycle. All HAP lines reached and maintained a rate of alcohol intake above the rate at which HAP1 mice metabolize alcohol, and BECs were consistent with this finding. Further, cHAP and HAP1 mice maintained an excessive level of intake throughout the dark portion of the cycle, accumulating mean BEC levels of 261.5 ± 18.09 and 217.9 ± 25.02 mg/dl, respectively. B6 mice drank comparatively modestly, and did not accumulate high BEC levels (53.63 + 8.15 mg/dl). Free-choice drinking demonstrated by the HAP1 and cHAP lines may provide a unique opportunity for modeling the excessive intake that often occurs in alcohol-dependent individuals, and allow for exploration of predisposing factors for excessive consumption, as well as the development of physiological, behavioral and toxicological outcomes following alcohol exposure. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  13. Concentration ratios for BIOPATH: selection of the soil-to-plant concentration ratio database

    International Nuclear Information System (INIS)

    Grogan, H.A.

    1985-01-01

    In Switzerland, high-level radioactive waste is planned to be deposited in deep crystalline formations. 'BIOPATH' is the computer code which has been used to simulate the movement of radionuclides in the biosphere, in order to calculate the doses to man. The key parameter used in the model on which the code is based is the concentration ratio (CR). This specifies the transfer of individual radionuclides via the various foodchains, ultimately to man. Five types of CR are required for the model, namely soil to plant, intake by cattle to milk, intake by cattle to meat, intake by poultry to eggs and from water to fish. Each of these CR are discussed in turn; it is shown that soil to plant CR exhibit a variability that greatly exceeds that observed in the other types of CR and for this reason the report goes on to consider these in much closer detail. The different methods and experimental techniques used to derive soil to plant CR are examined and assessed, to allow evaluation of a meaningful data base for use in BIOPATH. The report concludes by examining the data available for each radionuclide in turn and listing a recommended CR for it, to input into the BIOPATH model. (author)

  14. Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation.

    Science.gov (United States)

    Bengtsson-Palme, Johan; Larsson, D G Joakim

    2016-01-01

    There are concerns that selection pressure from antibiotics in the environment may accelerate the evolution and dissemination of antibiotic-resistant pathogens. Nevertheless, there is currently no regulatory system that takes such risks into account. In part, this is due to limited knowledge of environmental concentrations that might exert selection for resistant bacteria. To experimentally determine minimal selective concentrations in complex microbial ecosystems for all antibiotics would involve considerable effort. In this work, our aim was to estimate upper boundaries for selective concentrations for all common antibiotics, based on the assumption that selective concentrations a priori need to be lower than those completely inhibiting growth. Data on Minimal Inhibitory Concentrations (MICs) were obtained for 111 antibiotics from the public EUCAST database. The 1% lowest observed MICs were identified, and to compensate for limited species coverage, predicted lowest MICs adjusted for the number of tested species were extrapolated through modeling. Predicted No Effect Concentrations (PNECs) for resistance selection were then assessed using an assessment factor of 10 to account for differences between MICs and minimal selective concentrations. The resulting PNECs ranged from 8 ng/L to 64 μg/L. Furthermore, the link between taxonomic similarity between species and lowest MIC was weak. This work provides estimated upper boundaries for selective concentrations (lowest MICs) and PNECs for resistance selection for all common antibiotics. In most cases, PNECs for selection of resistance were below available PNECs for ecotoxicological effects. The generated PNECs can guide implementation of compound-specific emission limits that take into account risks for resistance promotion. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    Science.gov (United States)

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

    2015-07-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

  16. Comparative study on the selective chalcopyrite bioleaching of a molybdenite concentrate with mesophilic and thermophilic bacteria.

    Science.gov (United States)

    Romano, P; Blázquez, M L; Alguacil, F J; Muñoz, J A; Ballester, A; González, F

    2001-03-01

    This study evaluates different bioleaching treatments of a molybdenite concentrate using mesophilic and thermophilic bacterial cultures. Further studies on the chemical leaching and the electrochemical behavior of the MoS(2) concentrate were carried out. Bioleaching tests showed a progressive removal of chalcopyrite from the molybdenite concentrate with an increase in temperature. Chemical leaching tests support the idea of an indirect attack of the concentrate. Electrochemical tests indicate that chalcopyrite dissolution is favored when molybdenite is present. Therefore, this type of bioleaching treatment could be applied to purify molybdenite flotation concentrates by selectively dissolving chalcopyrite.

  17. Pharmacological Identification of a Guanidine-Containing β-Alanine Analogue with Low Micromolar Potency and Selectivity for the Betaine/GABA Transporter 1 (BGT1)

    DEFF Research Database (Denmark)

    Al-Khawaja, Anas Mohammad Ali; Petersen, Jette Gellert; Damgaard, Maria

    2014-01-01

    of the amino group in β-alanine or GABA, a series of compounds was generated, and their pharmacological activity assessed at human GAT subtypes. Using a cell-based [(3)H]GABA uptake assay, several selective inhibitors at human BGT1 were identified. The guanidine-containing compound 9 (2-amino-1......,4,5,6-tetrahydropyrimidine-5-carboxylic acid hydrochloride) displayed more than 250 times greater potency than the parent compound β-alanine at BGT1 and is thus the most potent inhibitor reported to date for this subtype (IC50 value of 2.5 µM). In addition, compound 9 displayed about 400, 16 and 40 times lower inhibitory...

  18. [Estimation of relation between homocysteine concentration and selected lipid parameters and adhesion molecules concentration in children with atherosclerosis risk factors].

    Science.gov (United States)

    Sierakowska-Fijałek, Anna; Baj, Zbigniew; Kaczmarek, Piotr; Stepień, Mariusz; Rysz, Jacek

    2008-10-01

    Atherosclerosis begins in childhood. At present among numerous risk factors of atherosclerosis the role of hiperhomocysteinemia in development of cardiovascular heart disease is taken under consideration. Atherogenic effect of homocystein is related to its cytotoxin action, conducting to endothelial dysfunction and damage. It is correlated with increase of the lipid levels in the blood serum and change of expression of the soluble forms of adhesion molecules. The aim of this study was to estimate relations between the homocystein serum concentration, expression of the selected adhesion molecules and the lipid levels in the blood serum in children with atherosclerosis risk factors. The group consisted of 670 children, 76 of them had atherosclerosis risk factors. In further examination 48 children have taken a part, whose parents were agreed for theirs participation in the program. The comparative group composed of 25 children without the risk factors. We determined total cholesterol (TC), triglycerides (TG), LDL cholesterol fraction (LDL-C), HDL cholesterol fraction (HDL-C), serum homocysteine concentration (Hcy), the expression of the soluble forms of adhesion molecules (sCAM): sP-selectin and sVCAM-1 (vascular cell adhesion molecule-1). Obesity, hypertension and lipid disorders in the shape of higher concentration of TC, LDL-C, TG and lower HDL-C were the most frequent risk factors in the investigated children. No significant differences in serum homocysteine concentration were observed between the investigated groups. However, its concentration was significantly higher in children with two atherosclerosis risk factors. No significant differences in expression of s-VCAM-1 were observed in the investigated groups, concentration of sP-selectin was significantly higher in children with atherosclerosis risk factors (phomocysteine and chosen adhesion molecules in children with atherosclerosis risk factors might potentially constitute the marker of early

  19. Selected Abstracts of the 2nd Congress of joint European Neonatal Societies (jENS 2017; Venice (Italy; October 31-November 4, 2017; Session "Perinatal Pharmacology and Anesthesia"

    Directory of Open Access Journals (Sweden)

    --- Various Authors

    2017-10-01

    Full Text Available Selected Abstracts of the 2nd Congress of joint European Neonatal Societies (jENS 2017; Venice (Italy; October 31-November 4, 201758th ESPR Annual Meeting, 7th International Congress of UENPS, 3rd International Congress of EFCNIORGANIZING INSTITUTIONSEuropean Society for Paediatric Research (ESPR, European Society for Neonatology (ESN, Union of European Neonatal & Perinatal Societies (UENPS, European Foundation for the Care of Newborn Infants (EFCNIORGANIZING COMMITTEELuc Zimmermann (President of ESPR, Morten Breindahl (President of ESN, Manuel Sánchez Luna (President of UENPS, Silke Mader (Chairwoman of the Executive Board and Co-Founder of EFCNISCIENTIFIC COMMITTEEVirgilio P. Carnielli (Congress President Chair, Pierre Gressens (Past Scientific President, Umberto Simeoni, Manon Benders, Neil Marlow, Ola D. Saugstad, Petra Hüppi, Agnes van den HoogenSession "Perinatal Pharmacology and Anesthesia"ABS 1. UNDERSTANDING THE RELATIONSHIP BETWEEN DOPAMINE CONCENTRATION AND BLOOD PRESSURE IN NEONATES: INCUBATORS VERSUS COT • K. Kirupakaran, H. Rabe, B. PatelABS 2. IBUPROFEN PHARMACOGENETIC STUDY IN HUMAN MILK SAMPLES • V. Rigourd, C. Verstyuft, J.F. Méritet, P. Seraissol, B. De Villepin, A. Amirouche, R. SerreauABS 3. EFFECT OF POSTNATAL CORTICOSTEROID ON BROWN ADIPOSE TISSUE THERMOGENESIS IN NEONATAL RAT • Y.-S. Chang, C.-H. Lin, Y.-S. TsaiABS 4. URINARY 17-α-HYDROXY-PROGESTERONE AS A POTENTIAL MARKER OF NEONATAL PAIN • M. Brasseler, T. HoehnABS 5. PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES AIMING FOR RATIONAL DRUG DOSING IN PRETERM NEONATES: THE DINO STUDY • R.B. Flint, S. Völler, R. de Groot, D. Liem, P. Andriessen, P. Degrauewe, I. Reiss, D. Burger, D. Tibboel, C.A.J. Knibbe, S.H.P. Simons and DINO Research groupABS 6. VENO-ARTERIAL EXTRACORPOREAL MEM­BRANE OXYGENATION IMPAIRS ACETYL­CHOLINE-INDUCED CONTRACTION IN NEONATAL PORCINE CORONARY ARTERIES • L. Provitera, G. Cavallaro, G. Raffaeli, I. Amodeo, S. Gulden, G. Zuanetti, V

  20. Use of mathematics to guide target selection in systems pharmacology; application to receptor tyrosine kinase (RTK) pathways.

    Science.gov (United States)

    Benson, Neil; van der Graaf, Piet H; Peletier, Lambertus A

    2017-11-15

    A key element of the drug discovery process is target selection. Although the topic is subject to much discussion and experimental effort, there are no defined quantitative rules around optimal selection. Often 'rules of thumb', that have not been subject to rigorous exploration, are used. In this paper we explore the 'rule of thumb' notion that the molecule that initiates a pathway signal is the optimal target. Given the multi-factorial and complex nature of this question, we have simplified an example pathway to its logical minimum of two steps and used a mathematical model of this to explore the different options in the context of typical small and large molecule drugs. In this paper, we report the conclusions of our analysis and describe the analysis tool and methods used. These provide a platform to enable a more extensive enquiry into this important topic. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. [Concentrations of alkaloids, cyanogenic glycosides, polyphenols and saponins in selected medicinal plants from Ecuador and their relationship with acute toxicity against Artemia salina].

    Science.gov (United States)

    Jaramillo Jaramillo, Carmita; Jaramillo Espinoza, Anyi; D'Armas, Haydelba; Troccoli, Luis; Rojas de Astudillo, Luisa

    2016-09-01

    Alkaloids, polyphenols, cyanogenic glycosides and saponins are among the main chemical compounds synthesized by plants but not considered essential for their basic metabolism. These compounds have different functions in plants, and have been recognized with medicinal and pharmacological properties. In this research, concentrations of the mentioned secondary metabolites were determined in the medicinal plants Artemisia absinthium, Cnidoscolus aconitifolius, Parthenium hysterophorus, Piper carpunya and Taraxacum officinale, from Ecuador, and related with cytotoxic effects against Artemia salina. Alcoholic and aqueous extracts from leaves of these selected plants were prepared at different concentrations. To assess cytotoxicity of these extracts, different bioassays with A. salina were undertaken, and the mortality rates and LC50 were obtained. Besides, concentrations of alkaloids, cyanogenic glycosides, phenols, tannins and saponins were determined by spectrophotometric methods; this constituted the first report of quantification of secondary metabolites in the selected plants from Ecuador. T. officinale had the highest concentration of total phenols (22.30 ± 0.23 mg/g) and tannins (11.70 ± 0.10 mg/g), C. aconitifolius of cyanogenic glycosides (5.02 ± 0.37 µg/g) and P. hysterophorus of saponins (6.12 ± 0.02 mg/g). Tannins values obtained were not adverse to their consumption. Alcoholic and aqueous extracts of selected plants had hemolytic activity depending on the concentration of saponins. Although the values of cyanogenic glycosides were permissible, it was necessary to monitor the presence of this metabolite in plants to minimize health problems. LC50 values ranged from extremely toxic (3.37 µg/mL) to highly toxic (274.34 μg/mL), in P. carpunya and T. officinale, respectively. From correlation analysis, it was observed that increase values of alkaloids concentrations had highly significant (pplants cytotoxicity decreased significantly (pplant extracts

  2. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a.

    Science.gov (United States)

    Deuis, Jennifer R; Dekan, Zoltan; Wingerd, Joshua S; Smith, Jennifer J; Munasinghe, Nehan R; Bhola, Rebecca F; Imlach, Wendy L; Herzig, Volker; Armstrong, David A; Rosengren, K Johan; Bosmans, Frank; Waxman, Stephen G; Dib-Hajj, Sulayman D; Escoubas, Pierre; Minett, Michael S; Christie, Macdonald J; King, Glenn F; Alewood, Paul F; Lewis, Richard J; Wood, John N; Vetter, Irina

    2017-01-20

    Human genetic studies have implicated the voltage-gated sodium channel Na V 1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na V 1.7 (IC 50 0.9 nM) with at least 40-1000-fold selectivity over all other Na V subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na V 1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na V 1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na V 1.7 inhibitors produced profound analgesia. Our results suggest that in these inflammatory models, acute administration of peripherally restricted Na V 1.7 inhibitors can only produce analgesia when administered in combination with an opioid.

  3. Catecholic amides as potential selective phosphodiesterase 4D inhibitors: Design, synthesis, pharmacological evaluation and structure-activity relationships.

    Science.gov (United States)

    Zhou, Zhong-Zhen; Ge, Bing-Chen; Chen, Yu-Fang; Shi, Xiu-Dong; Yang, Xue-Mei; Xu, Jiang-Ping

    2015-11-15

    In this study, a series of catechol-based amides (8a-n) with different amide linkers linking the catecholic moiety to the terminal phenyl ring was designed and synthesized as potent phosphodiesterase (PDE) 4D inhibitors. The inhibitory activities of these compounds were evaluated against the core catalytic domains of human PDE4 (PDE4CAT), full-length PDE4B1 and PDE4D7 enzymes, and other PDE family members. The results indicated the majority of compounds 8a-n displayed moderate to good inhibitory activities against PDE4CAT. Among these compounds, compound 8 j with a short amide linker (-CONHCH2-) displayed comparable PDE4CAT inhibitory activity (IC50=410 nM) with rolipram. More interestingly, compound 8 g, a potent and selective PDE4D inhibitor (IC50=94 nM), exhibited a 10-fold selectivity over the PDE4B subtypes and an over 1000-fold selectivity against other PDE family members. Docking simulations suggested that 8 g forms three extra H-bonds with the N-H of residue Asn487 and two water molecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. [Pharmacological treatment].

    Science.gov (United States)

    Arriola Manchola, Enrique; Álaba Trueba, Javier

    2016-06-01

    Alzheimer's disease (AD) is a chronic degenerative and inflammatory process leading to synapticdysfunction and neuronal death. A review about the pharmacological treatment alternatives is made: acetylcholinesterase inhibitors (AChEI), a nutritional supplement (Souvenaid) and Ginkgo biloba. A special emphasis on Ginkgo biloba due to the controversy about its use and the approval by the European Medicines Agency is made. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a

    OpenAIRE

    Deuis, J. R.; Dekan, Z.; Wingerd, J. S.; Smith, J. J.; Munasinghe, N. R.; Bhola, R. F.; Imlach, W. L.; Herzig, V.; Armstrong, D. A.; Rosengren, K. J.; Bosmans, F.; Waxman, S. G.; Dib-Hajj, S. D.; Escoubas, P.; Minett, M. S.

    2017-01-01

    Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV1.7 (IC50 0.9 nM) with at least 40-1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV1.7 activation, Pn3a alone displayed...

  6. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a

    OpenAIRE

    Jennifer R. Deuis; Zoltan Dekan; Joshua S. Wingerd; Jennifer J. Smith; Nehan R. Munasinghe; Rebecca F. Bhola; Wendy L. Imlach; Volker Herzig; David A. Armstrong; K. Johan Rosengren; Frank Bosmans; Stephen G. Waxman; Sulayman D. Dib-Hajj; Pierre Escoubas; Michael S. Minett

    2017-01-01

    Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, ?-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV1.7 (IC50 0.9?nM) with at least 40?1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV1.7 activation, Pn3a alone displayed...

  7. Concentrations and geographic distribution of selected organic pollutants in Scottish surface soils

    International Nuclear Information System (INIS)

    Rhind, S.M.; Kyle, C.E.; Kerr, C.; Osprey, M.; Zhang, Z.L.; Duff, E.I.; Lilly, A.; Nolan, A.; Hudson, G.; Towers, W.; Bell, J.; Coull, M.; McKenzie, C.

    2013-01-01

    Concentrations of selected persistent organic pollutants (POPs) representing three chemical classes (polycyclic aromatic hydrocarbons (PAH), polybrominated diphenyl ethers (PBDE) and polychlorinated biphenyls (PCB) and the organic pollutant diethylhexyl phthalate (DEHP), were determined in surface soil samples (0–5 cm) collected at 20 km grid intersects throughout Scotland over a three-year period. Detectable amounts of all chemical classes and most individual congeners were present in all samples. There were no consistent effects of soil or vegetation type, soil carbon content, pH, altitude or distance from centres of population on concentrations which exhibited extreme variation, even in adjacent samples. It is concluded that soil POPs and DEHP concentrations and associated rates of animal and human exposure were highly variable, influenced by multiple, interacting factors, and not clearly related to local sources but possibly related to wet atmospheric deposition and the organic carbon content of the soil. -- Highlights: •Concentrations of selected organic pollutants in Scottish soils were determined. •Concentrations were highly variable. •There were few effects of soil or vegetation type, soil carbon, pH or altitude. •Distance from cities was not an important determinant of concentrations. •Atmospheric deposition and soil organic carbon content may affect concentrations. -- Soil concentrations of anthropogenic persistent organic pollutants are not clearly related to soil type or pH, vegetation, altitude, or distance from pollutant sources

  8. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors.

    Science.gov (United States)

    Blake, James F; Xu, Rui; Bencsik, Josef R; Xiao, Dengming; Kallan, Nicholas C; Schlachter, Stephen; Mitchell, Ian S; Spencer, Keith L; Banka, Anna L; Wallace, Eli M; Gloor, Susan L; Martinson, Matthew; Woessner, Richard D; Vigers, Guy P A; Brandhuber, Barbara J; Liang, Jun; Safina, Brian S; Li, Jun; Zhang, Birong; Chabot, Christine; Do, Steven; Lee, Leslie; Oeh, Jason; Sampath, Deepak; Lee, Brian B; Lin, Kui; Liederer, Bianca M; Skelton, Nicholas J

    2012-09-27

    The discovery and optimization of a series of 6,7-dihydro-5H-cyclopenta[d]pyrimidine compounds that are ATP-competitive, selective inhibitors of protein kinase B/Akt is reported. The initial design and optimization was guided by the use of X-ray structures of inhibitors in complex with Akt1 and the closely related protein kinase A. The resulting compounds demonstrate potent inhibition of all three Akt isoforms in biochemical assays and poor inhibition of other members of the cAMP-dependent protein kinase/protein kinase G/protein kinase C extended family and block the phosphorylation of multiple downstream targets of Akt in human cancer cell lines. Biological studies with one such compound, 28 (GDC-0068), demonstrate good oral exposure resulting in dose-dependent pharmacodynamic effects on downstream biomarkers and a robust antitumor response in xenograft models in which the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway is activated. 28 is currently being evaluated in human clinical trials for the treatment of cancer.

  9. Selective Granulocyte and Monocyte Apheresis as a Non-Pharmacological Option for Patients with Inflammatory Bowel Disease

    Science.gov (United States)

    C. Leitner, Gerda; Worel, Nina; Vogelsang, Harald

    2012-01-01

    Ulcerative colitis and Crohn's disease are the two most prevalent inflammatory bowel diseases. In both cases, the medically refractory and steroid-dependent type presents a therapeutic challenge. To help resolve this problem, a mainly Japanese team developed a new therapeutic option. There are two systems, both of which are able to selectively remove the main mediators of the disease, namely the activated pro-inflammatory cytokine-producing granulocytes and monocytes/macrophages, from the patient's blood circulation (GMA = granulocyte monocyte apheresis). One of the two systems is the Adacolumn® (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and a single-use column, which contains approximately 35,000 cellulose acetate beads. The exact mode of action is not yet sufficiently understood, but however, a modulation of the immune system takes place. As a result, less pro-inflammatory cytokines are released. Furthermore, the production of anti-inflammatory interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to the inflamed tissue, and CD10-negative immature granulocytes appear in the peripheral blood. Another effect to be mentioned is the removal of the peripheral dendritic cells and the leachate of regulatory T cells (T-regs). The second system is the Cellsorba® FX Filter (Asahi Medical, Tokyo, Japan). The range of efficiency, the indication, and the procedure are very similar to the Adacolumn. Solely the additional removal of lymphocytes can possibly limit the implementation since lymphopenia can increase the risk of autoimmune disease. Both systems provide a low-risk therapy with few adverse reactions. ASFA recommendations for GMA in inflammatory bowel disease are 2B due to the fact that not enough randomized double-blind studies are available to proof the efficacy of this treatment. PMID:22969694

  10. Low concentrations of metal mixture exposures have adverse effects on selected biomarkers of Xenopus laevis tadpoles

    Energy Technology Data Exchange (ETDEWEB)

    Yologlu, Ertan, E-mail: ertanyologlu82@gmail.com [Adiyaman University, Faculty of Education, Department of Science Education, 02040 Adiyaman (Turkey); Ozmen, Murat [Inonu University, Laboratory of Environmental Toxicology, Department of Biology, Faculty of Arts & Science, 44280 Malatya (Turkey)

    2015-11-15

    Highlights: • Selected metal mixtures were evaluated for toxicity of safety limit concentrations. • Xenopus laevis tadpoles were used as model test organism. • Combinations of LC{sub 50} and LC{sub 50}/2 caused 100% lethality for some metals. • Metals did not change metallothionein levels in low concentrations. • Selected enzyme activities showed induction after low concentration exposures. - Abstract: Polluted ecosystems may contain mixtures of metals, such that the combinations of metals, even in low concentrations, may cause adverse effects. In the present study, we focused on toxic effects of mixtures of selected metals, the LC{sub 50} values, and also their safety limit in aquatic systems imposed by the European legislation using a model organism. Xenopus laevis tadpoles were used as test organisms. They were exposed to metals or their combinations due to 96-h LC{sub 50} values. Glutathione S-transferase (GST), glutathione reductase (GR), acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione peroxidase (GPx), and catalase (CAT) levels were evaluated. Metallothionein concentrations were also determined. The LC{sub 50}s for Cd, Pb, and Cu were calculated as 5.81 mg AI/L, 123.05 mg AI/L, and 0.85 mg AI/L, respectively. Low lethality ratios were observed with unary exposure of each metal in lower concentrations. Double or triple combinations of LC{sub 50} and LC{sub 50}/2 concentrations caused 100% lethality with Cd + Cu and Pb + Cd + Cu mixtures, while the Pb + Cu mixture also caused high lethal ratios. The selected enzyme activities were significantly affected by metals or mixtures, and dose-related effects were determined. The metallothionein levels generally increased as related to concentration in unary metals and mixtures. Acceptable limit values of unary metals and mixtures did not significantly change metallothionein levels. The results suggest that oxidative stress-related mechanisms are involved in the toxicity induced by selected

  11. Selection of common bean lines with high grain yield and high grain calcium and iron concentrations

    Directory of Open Access Journals (Sweden)

    Nerinéia Dalfollo Ribeiro

    2014-02-01

    Full Text Available Genetic improvement of common bean nutritional quality has advantages in marketing and can contribute to society as a food source. The objective of this study was to evaluate the genetic variability for grain yield, calcium and iron concentrations in grains of inbred common bean lines obtained by different breeding methods. For this, 136 F7 inbred lines were obtained using the Pedigree method and 136 F7 inbred lines were obtained using the Single-Seed Descent (SSD method. The lines showed genetic variability for grain yield, and concentrations of calcium and iron independently of the method of advancing segregating populations. The Pedigree method allows obtaining a greater number of lines with high grain yield. Selection using the SSD method allows the identification of a larger number of lines with high concentrations of calcium and iron in grains. Weak negative correlations were found between grain yield and calcium concentration (r = -0.0994 and grain yield and iron concentration (r = -0.3926. Several lines show genetic superiority for grain yield and concentrations of calcium and iron in grains and their selection can result in new common bean cultivars with high nutritional quality.

  12. Risk assessment of radon gas concentration for some selected offices of KNUST campus, Kumasi

    International Nuclear Information System (INIS)

    Bediako, Yaw Addo

    2013-11-01

    Radon (Rn-222) has been identified as an factor that could result in a health hazard by studies all around the world. The health risks can be minimised by preventing measures where radon is highly concentrated as in some mines or homes or offices. A study in the buildup concentration of the inert gas, will give us a better understanding of its possible pathways through soil into the air surrounding and offices where radon releases can become hazardous. Measuring the radon concentrations on campus, can help to deduce the radon flux to identify the problem areas for rehabilitation. An active method incorporating Trace level radon gas detection and continious monitoring method was used in this study to determine the radon concentration of the selected offices. Concentrations ranging from 0.010 to 0.498 pCi/I were detected, with the head of optometry and Visual Science recording the highest concentration of 0.498 pCi/I, while the head of Agricultural Engineering Department office with the least concentration of 0.010 pCi/I. Although these concentrations are generally low as compared with the EPA guidelines of an action level of 4 pCi/I, but no amount of radiation is said to be safe. (au)

  13. Determination of the radon Concentration in underground water in selected areas in and around Kumasi

    International Nuclear Information System (INIS)

    Owusu, Seth Adjei

    2012-06-01

    Radon (Rn-222) is a radioactive noble gas of natural origin that may be found anywhere in soil, air and different types of water: surface, borehole, well and spring. It is worth to carry out surveys for the radon in water for radiation protection as well as for geological considerations. The research presenters here was carried out in selected towns in and around Kumasi for the determination of radon concentration in groundwater. The major towns from which samples were taken are , Mowire, Kronum, Aburaso, Medoma, Kenyase, Buokrom, Bomfa, Ayeduase, Kotei, Tikrom. All the samples are used for domestic purposes such as cooking, drinking, bathing and washing. Waters from boreholes and wells in the selected towns were sampled and the radon concentration level measured. The Roll’s method was used for the radon concentration analysis on all the 100 samples. The results shows that, the minimum radon concentration in groundwater was 13015.934 Bq/m3 and it was found at Bomfa, and the highest was found to be 964628.480 Bq/m3, recorded at Mowire. It is believed that this variation of levels is mainly due to the difference in rock type, soil type and geology of the area as well as the depth of the water samples. This information can be used to estimate the possible health hazards from radon in the selected towns in the future from environmental point of view. The data would promote public awareness related to risk of radon exposure. (au)

  14. Pharmacodynamic Model To Describe the Concentration-Dependent Selection of Cefotaxime-Resistant Escherichia coli

    Science.gov (United States)

    Olofsson, Sara K.; Geli, Patricia; Andersson, Dan I.; Cars, Otto

    2005-01-01

    Antibiotic dosing regimens may vary in their capacity to select mutants. Our hypothesis was that selection of a more resistant bacterial subpopulation would increase with the time within a selective window (SW), i.e., when drug concentrations fall between the MICs of two strains. An in vitro kinetic model was used to study the selection of two Escherichia coli strains with different susceptibilities to cefotaxime. The bacterial mixtures were exposed to cefotaxime for 24 h and SWs of 1, 2, 4, 8, and 12 h. A mathematical model was developed that described the selection of preexisting and newborn mutants and the post-MIC effect (PME) as functions of pharmacokinetic parameters. Our main conclusions were as follows: (i) the selection between preexisting mutants increased with the time within the SW; (ii) the emergence and selection of newborn mutants increased with the time within the SW (with a short time, only 4% of the preexisting mutants were replaced by newborn mutants, compared to the longest times, where 100% were replaced); and (iii) PME increased with the area under the concentration-time curve (AUC) and was slightly more pronounced with a long elimination half-life (T1/2) than with a short T1/2 situation, when AUC is fixed. We showed that, in a dynamic competition between strains with different levels of resistance, the appearance of newborn high-level resistant mutants from the parental strains and the PME can strongly affect the outcome of the selection and that pharmacodynamic models can be used to predict the outcome of resistance development. PMID:16304176

  15. A selective electrocatalyst-based direct methanol fuel cell operated at high concentrations of methanol.

    Science.gov (United States)

    Feng, Yan; Liu, Hui; Yang, Jun

    2017-06-01

    Owing to the serious crossover of methanol from the anode to the cathode through the polymer electrolyte membrane, direct methanol fuel cells (DMFCs) usually use dilute methanol solutions as fuel. However, the use of high-concentration methanol is highly demanded to improve the energy density of a DMFC system. Instead of the conventional strategies (for example, improving the fuel-feed system, membrane development, modification of electrode, and water management), we demonstrate the use of selective electrocatalysts to run a DMFC at high concentrations of methanol. In particular, at an operating temperature of 80°C, the as-fabricated DMFC with core-shell-shell Au@Ag 2 S@Pt nanocomposites at the anode and core-shell Au@Pd nanoparticles at the cathode produces a maximum power density of 89.7 mW cm -2 at a methanol feed concentration of 10 M and maintains good performance at a methanol concentration of up to 15 M. The high selectivity of the electrocatalysts achieved through structural construction accounts for the successful operation of the DMFC at high concentrations of methanol.

  16. A selective electrocatalyst–based direct methanol fuel cell operated at high concentrations of methanol

    Science.gov (United States)

    Feng, Yan; Liu, Hui; Yang, Jun

    2017-01-01

    Owing to the serious crossover of methanol from the anode to the cathode through the polymer electrolyte membrane, direct methanol fuel cells (DMFCs) usually use dilute methanol solutions as fuel. However, the use of high-concentration methanol is highly demanded to improve the energy density of a DMFC system. Instead of the conventional strategies (for example, improving the fuel-feed system, membrane development, modification of electrode, and water management), we demonstrate the use of selective electrocatalysts to run a DMFC at high concentrations of methanol. In particular, at an operating temperature of 80°C, the as-fabricated DMFC with core-shell-shell Au@Ag2S@Pt nanocomposites at the anode and core-shell Au@Pd nanoparticles at the cathode produces a maximum power density of 89.7 mW cm−2 at a methanol feed concentration of 10 M and maintains good performance at a methanol concentration of up to 15 M. The high selectivity of the electrocatalysts achieved through structural construction accounts for the successful operation of the DMFC at high concentrations of methanol. PMID:28695199

  17. Study of Selected Composites Copper Concentrate-Plastic Waste Using Thermal Analysis

    Science.gov (United States)

    Szyszka, Danuta

    2017-12-01

    The paper presents thermal analysis of selected composites (copper concentrate, plastic waste) in two stages. The first stage consisted in thermogravimetric analysis and differential thermal analysis on the applied plastic waste and copper concentrate, and subsequently, a comparative study has been carried out on products obtained, constituting composites of those materials. As a result of analyses, it was found that up to ca. 400 °C composites show high thermal stability, whereas above that temperature, a thermal decomposition of the composite occurs, resulting in emissions of organic compounds, i.e. hydrocarbon compounds and organic oxygenate derivatives.

  18. Concentrations and risk assessment of selected monoaromatic hydrocarbons in buses and bus stations of Hangzhou, China.

    Science.gov (United States)

    Li, Shuang; Chen, Shuguang; Zhu, Lizhong; Chen, Xiasheng; Yao, Chaoying; Shen, Xueyou

    2009-03-01

    Air pollution surveys of ten selected monoaromatic hydrocarbons (MAHCs) were conducted in buses and bus stations in Hangzhou, China. The mean concentrations of MAHCs in the air of buses and bus stations were 95.9 and 36.5 microg/m(3), respectively, of which toluene was the highest in all the sampling sites. Mean concentrations of all MAHCs in buses were statistically higher than those nearby bus stations (pbus drivers were 1.11x10(-5) and 4.00x10(-5), respectively, which were way above the limit set by USEPA. The health risk caused by MAHCs in bus microenvironment should be cautioned.

  19. Selective exploitation of large pike Esox lucius-Effects on mercury concentrations in fish populations

    International Nuclear Information System (INIS)

    Sharma, Chhatra Mani; Borgstrom, Reidar; Huitfeldt, Jorgen Sinkaberg; Rosseland, Bjorn Olav

    2008-01-01

    The present study outlines two main trends of mercury transfer patterns through the fish community: 1) the Hg concentrations increase with increase in the trophic level, with top predators having the highest concentrations, and 2) a fast growth rate may dilute the concentrations of Hg in fish muscle tissue (growth biodilution). In 2004, an extensive reduction in number of large pike (Esox lucius L.), was initiated by selective gillnet fishing in Lake Arungen, Norway, in order to increase the pike recruitment due to an expected reduction in cannibalism. In this connection, total mercury (THg) concentrations in the fish community were studied both before (2003) and after (2005) the removal of large pike. The δ 15 N signatures and stomach content analyses indicated that pike and perch (Perca fluviatilis L.) occupied the highest trophic position, while roach (Rutilus rutilus (L.)) was at the lower level, and rudd (Scardinius erythrophthalmus L.) at the lowest. The piscivores, pike and perch, had the highest concentrations of THg. The biomagnification rate of THg through the food web in the fish community was 0.163 ( per milleδ 15 N), with the highest uptake rate (0.232) in perch. A significant decrease in THg concentrations was found in all fish species in 2005 compared to 2003. Removal of the top predators in an Hg contaminated lake might thus be an important management tool for reducing Hg levels in fish, thereby reducing health risk to humans

  20. Energetical optimization and parameters selection for a fixed faceted mirror concentrator

    International Nuclear Information System (INIS)

    Nicolas, R.O.; Duran, J.C.; Dawidowski, L.E.

    1990-01-01

    A method which allows to select the parameters of a cylindrical solar collector by means of an energetical optimization is presented. In particular, the energy collected by the operating fluid and the collection efficiency of a Fixed Faceted Mirror Concentrator (FFMC) are obtained and compared for different sets of parameters. To this end, the two-dimensional optical analysis for non-perfect cylindrical concentrators presented previously is used. Some graphs analyzing the variations of the yearly efficiency of the FFMC as a function of those parameters are given. Finally, the possibility of using a second concentrator in the receiver plane of the FFMC in order to improve the whole efficiency of the prototype is also analyzed. (Author)

  1. High-dimensional orbital angular momentum entanglement concentration based on Laguerre–Gaussian mode selection

    International Nuclear Information System (INIS)

    Zhang, Wuhong; Su, Ming; Wu, Ziwen; Lu, Meng; Huang, Bingwei; Chen, Lixiang

    2013-01-01

    Twisted photons enable the definition of a Hilbert space beyond two dimensions by orbital angular momentum (OAM) eigenstates. Here we propose a feasible entanglement concentration experiment, to enhance the quality of high-dimensional entanglement shared by twisted photon pairs. Our approach is started from the full characterization of entangled spiral bandwidth, and is then based on the careful selection of the Laguerre–Gaussian (LG) modes with specific radial and azimuthal indices p and ℓ. In particular, we demonstrate the possibility of high-dimensional entanglement concentration residing in the OAM subspace of up to 21 dimensions. By means of LabVIEW simulations with spatial light modulators, we show that the Shannon dimensionality could be employed to quantify the quality of the present concentration. Our scheme holds promise in quantum information applications defined in high-dimensional Hilbert space. (letter)

  2. Pharmacological effects of biotin.

    Science.gov (United States)

    Fernandez-Mejia, Cristina

    2005-07-01

    In the last few decades, more vitamin-mediated effects have been discovered at the level of gene expression. Increasing knowledge on the molecular mechanisms of these vitamins has opened new perspectives that form a connection between nutritional signals and the development of new therapeutic agents. Besides its role as a carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme that stimulates glucose production by the liver. The findings that biotin regulates the expression of genes that are critical in the regulation of intermediary metabolism are in agreement with several observations that indicate that biotin supply is involved in glucose and lipid homeostasis. Biotin deficiency has been linked to impaired glucose tolerance and decreased utilization of glucose. On the other hand, the diabetic state appears to be ameliorated by pharmacological doses of biotin. Likewise, pharmacological doses of biotin appear to decrease plasma lipid concentrations and modify lipid metabolism. The effects of biotin on carbohydrate metabolism and the lack of toxic effects of the vitamin at pharmacological doses suggest that biotin could be used in the development of new therapeutics in the treatment of hyperglycemia and hyperlipidemia, an area that we are actively investigating.

  3. Selective removal of arsenic and monovalent ions from brackish water reverse osmosis concentrate.

    Science.gov (United States)

    Xu, Pei; Capito, Marissa; Cath, Tzahi Y

    2013-09-15

    Concentrate disposal and management is a considerable challenge for the implementation of desalination technologies, especially for inland applications where concentrate disposal options are limited. This study has focused on selective removal of arsenic and monovalent ions from brackish groundwater reverse osmosis (RO) concentrate for beneficial use and safe environmental disposal using in situ and pre-formed hydrous ferric oxides/hydroxides adsorption, and electrodialysis (ED) with monovalent permselective membranes. Coagulation with ferric salts is highly efficient at removing arsenic from RO concentrate to meet a drinking water standard of 10 μg/L. The chemical demand for ferric chloride however is much lower than ferric sulfate as coagulant. An alternative method using ferric sludge from surface water treatment plant is demonstrated as an efficient adsorbent to remove arsenic from RO concentrate, providing a promising low cost, "waste treat waste" approach. The monovalent permselective anion exchange membranes exhibit high selectivity in removing monovalent anions over di- and multi-valent anions. The transport of sulfate and phosphate through the anion exchange membranes was negligible over a broad range of electrical current density. However, the transport of divalent cations such as calcium and magnesium increases through monovalent permselective cation exchange membranes with increasing current density. Higher overall salt concentration reduction is achieved around limiting current density while higher normalized salt removal rate in terms of mass of salt per membrane area and applied energy is attained at lower current density because the energy unitization efficiency decreases at higher current density. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity

    Directory of Open Access Journals (Sweden)

    Jonathan eShelton

    2015-01-01

    Full Text Available Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6 induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg. Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15 or advance (CT22 wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light-induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals.

  5. Determination of uranium metal concentration in irradiated fuel storage basin sludge using selective dissolution

    International Nuclear Information System (INIS)

    Delegard, C.H.; Sinkov, S.I.; Chenault, J.W.; Schmidt, A.J.; Pool, K.N.; Welsh, T.L.

    2014-01-01

    Irradiated uranium metal fuel was stored underwater in the K East and K West storage basins at the US Department of Energy Hanford Site. The uranium metal under damaged cladding reacted with water to generate hydrogen gas, uranium oxides, and spalled uranium metal particles which intermingled with other particulates to form sludge. While the fuel has been removed, uranium metal in the sludge remains hazardous. An expeditious routine method to analyze 0.03 wt% uranium metal in the presence of >30 wt% total uranium was needed to support safe sludge management and processing. A selective dissolution method was designed based on the rapid uranium oxide dissolution but very low uranium metal corrosion rates in hot concentrated phosphoric acid. The uranium metal-bearing heel from the phosphoric acid step then is rinsed before the uranium metal is dissolved in hot concentrated nitric acid for analysis. Technical underpinnings of the selective dissolution method, including the influence of sludge components, were investigated to design the steps and define the reagents, quantities, concentrations, temperatures, and times within the selective dissolution analysis. Tests with simulant sludge proved the technique feasible. Tests with genuine sludge showed a 0.0028 ± 0.0037 wt% (at one standard deviation) uranium metal analytical background, a 0.011 wt% detection limit, and a 0.030 wt% quantitation limit in settled (wet) sludge. In tests using genuine K Basin sludge spiked with uranium metal at concentrations above the 0.030 wt% ± 25 % (relative) quantitation limit, uranium metal recoveries averaged 99.5 % with a relative standard deviation of 3.5 %. (author)

  6. Concentration-mortality responses of Myzus persicae and natural enemies to selected insecticides.

    Science.gov (United States)

    Bacci, Leandro; Rosado, Jander F; Picanço, Marcelo C; Pereira, Eliseu J G; Silva, Gerson A; Martins, Júlio C

    2012-01-01

    The toxicity of six insecticides was determined for the peach-potato aphid, Myzus persicae (Hemiptera: Aphididae), and some of its natural enemies - the predatory beetles Cycloneda sanguinea (Coccinellidae) and Acanthinus sp. (Anthicidae), and the wasp parasitoid Diaeretiella rapae (Aphidiidae). Natural enemies from these groups are important natural biological control agents in a number of agroecosystems, and insecticides potentially safe to these non-target organisms should be identified using standardized tests. Thus, concentration-mortality bioassays were carried out with both the aphid and its natural enemies to assess the toxicity and selectivity of acephate, deltamethrin, dimethoate, methamidophos, methyl parathion, and pirimicarb. The latter insecticide was highly selective to all natural enemies tested, and its LC(90) for M. persicae was 14-fold lower than the field rate recommended for control of the aphid in brassica crops. Methyl parathion also showed selectivity to C. sanguinea and Acanthinus sp., but not to D. rapae. Acephate was the least potent insecticide against M. persicae and was equally or more toxic to the natural enemies relative to the aphid. Pirimicarb and methyl parathion were efficient against M. persicae and selective in favor of two of the natural enemies tested. Acanthinus sp. and C. sanguinea were more tolerant to the insecticides than was the parasitoid D. rapae. This study shows that there are selective insecticides that may be compatible with conservation of natural enemies in brassica crops, which is important practical information to improve integrated pest management systems in these crops.

  7. Fabrication and comparison of selective, transparent optics for concentrating solar systems

    Science.gov (United States)

    Taylor, Robert A.; Hewakuruppu, Yasitha; DeJarnette, Drew; Otanicar, Todd P.

    2015-09-01

    Concentrating optics enable solar thermal energy to be harvested at high temperature (solar) wavelengths, but highly reflective at long (thermal emission) wavelengths. If a solar system requires an analogous transparent, non-absorbing optic - i.e. a cover material which is highly transparent at short wavelengths, but highly reflective at long wavelengths - the technology is simply not available. Low-e glass technology represents a commercially viable option for this sector, but it has only been optimized for visible light transmission. Optically thin metal hole-arrays are another feasible solution, but are often difficult to fabricate. This study investigates combinations of thin film coatings of transparent conductive oxides and nanoparticles as a potential low cost solution for selective solar covers. This paper experimentally compares readily available materials deposited on various substrates and ranks them via an `efficiency factor for selectivity', which represents the efficiency of radiative exchange in a solar collector. Out of the materials studied, indium tin oxide and thin films of ZnS-Ag-ZnS represent the most feasible solutions for concentrated solar systems. Overall, this study provides an engineering design approach and guide for creating scalable, selective, transparent optics which could potentially be imbedded within conventional low-e glass production techniques.

  8. Application of tripolar concentric electrodes and prefeature selection algorithm for brain-computer interface.

    Science.gov (United States)

    Besio, Walter G; Cao, Hongbao; Zhou, Peng

    2008-04-01

    For persons with severe disabilities, a brain-computer interface (BCI) may be a viable means of communication. Lapalacian electroencephalogram (EEG) has been shown to improve classification in EEG recognition. In this work, the effectiveness of signals from tripolar concentric electrodes and disc electrodes were compared for use as a BCI. Two sets of left/right hand motor imagery EEG signals were acquired. An autoregressive (AR) model was developed for feature extraction with a Mahalanobis distance based linear classifier for classification. An exhaust selection algorithm was employed to analyze three factors before feature extraction. The factors analyzed were 1) length of data in each trial to be used, 2) start position of data, and 3) the order of the AR model. The results showed that tripolar concentric electrodes generated significantly higher classification accuracy than disc electrodes.

  9. State test-anxiety, selective attention and concentration in university students.

    Science.gov (United States)

    Fernández-Castillo, Antonio; Caurcel, María J

    2015-08-01

    The principal aim of this study was to assess the level of selective attention and mental concentration before exams in a sample of university students and to determine a possible relationship between anxiety and reduction of levels of attention in this circumstance. A total of 403 university students, 176 men and 227 women, aged from 18 to 46 years, participated in the study. Of them, 169 were first-year undergraduates, 118 were second to fourth-year undergraduates and 116 were postgraduate Master's degree students. All of them completed the Spanish version of the Spielberger State-Anxiety Inventory and the D2 Attention Test just before taking an exam. Our results showed that participants with lower levels of anxiety had higher levels of selective attention and mental concentration before the exam. These results specifically indicate that when anxiety levels are very high, this could over-activate the orientating and alerting functions and to reduce the capacity of attentional control. These processes could have a negative impact on specific attentional processes and become a negative influence on performance in exams. © 2014 International Union of Psychological Science.

  10. Prediction of Coal Face Gas Concentration by Multi-Scale Selective Ensemble Hybrid Modeling

    Directory of Open Access Journals (Sweden)

    WU Xiang

    2014-06-01

    Full Text Available A selective ensemble hybrid modeling prediction method based on wavelet transformation is proposed to improve the fitting and generalization capability of the existing prediction models of the coal face gas concentration, which has a strong stochastic volatility. Mallat algorithm was employed for the multi-scale decomposition and single-scale reconstruction of the gas concentration time series. Then, it predicted every subsequence by sparsely weighted multi unstable ELM(extreme learning machine predictor within method SERELM(sparse ensemble regressors of ELM. At last, it superimposed the predicted values of these models to obtain the predicted values of the original sequence. The proposed method takes advantage of characteristics of multi scale analysis of wavelet transformation, accuracy and fast characteristics of ELM prediction and the generalization ability of L1 regularized selective ensemble learning method. The results show that the forecast accuracy has large increase by using the proposed method. The average relative error is 0.65%, the maximum relative error is 4.16% and the probability of relative error less than 1% reaches 0.785.

  11. Relationships between mercury concentration and food selectivity of many kinds of fishes in Minamata Bay

    Science.gov (United States)

    Mori, K.; Kanaya, G.

    2016-02-01

    Serious injuries occurred in residents who consumed fish and shellfishes in Minamata Bay polluted by high-concentration methyl-mercury in the 1950s. Pollution has fallen to a safe level because of the pollution prevention project (dredging etc.) carried out from 1977 to 1990. From 2010 we have been researching the bioaccumulation of mercury in several fishes in Minamata Bay and surrounding areas. We selected several sampling points that showed different environmental conditions, species composition and food web patterns. For the determination of feeding types of 60 species fishes (600 samples) sampled by gill net, we measured mercury levels of each sample and directly checked food items in gut, and distinguished carnivore, omnivore, herbivore and detritivore. At this time, we introduced a stable isotope analysis for checking the food history and feeding habits of dominant fish. In about 300 individuals of 30 species of dominant fish selected from the 600 samples, we measured the stable nitrogen and carbon isotope ratios (δ15N, δ13C) of each sample. Checking the food items in gut of fishes, more than 80% of fishes were carnivorous, and showed different selectivity of food items, such as fish, crustacean and so on. From the results of stable isotope ratios, benthic fish tended to show a higher ratio of δ13C. Usually benthic microalgae evidenced a higher ratio of δ13C than planktonic microalgae, and the ratio conservative through the food chain. In general, δ15N increases through the food chain with +3 to +4 ‰ enrichment per trophic step. In these data, carnivorous fishes of benthic and pelagic type showed medium and high ratios of δ15N. From comparing the stable isotope ratio to the mercury concentration of fishes, all of the high-mercury fishes belonged to benthic and carnivorous types. We consider the joint method of food web analysis and stable isotope analysis to be useful for understanding the mechanism of mercury bioaccumulation through the food web

  12. Bisphenol A and alkylphenols concentrations in selected mariculture fish species from Pulau Kukup, Johor, Malaysia.

    Science.gov (United States)

    Ismail, Nur Afifah Hanun; Wee, Sze Yee; Aris, Ahmad Zaharin

    2018-02-01

    Endocrine disrupting compound (EDC) contamination in food is a global concern. Concerning potential environmental and human health exposed to EDCs via food intake, an experiment was conducted on the selected EDCs concentration in the mariculture fish, Trachinotus blochii (golden pomfret), Lutjanus campechanus (snapper), and Lates calcarifer (sea bass) at Pulau Kukup, Johor. Mariculture activity at Pulau Kukup involves active export of fishes to Singapore and Indonesia. The recovery of BPA (bisphenol A), 4OP (4-octylphenol), and 4NP (4-nonylphenol) were 61.54%-93.00%, 16.79%-17.13%, and 61.24%-71.49%, respectively. Relatively high concentration of BPA was recorded in T. blochii (0.322ng/g), followed by L. calcarifer (0.124ng/g) and L. campechanus (0.023ng/g). Furthermore, 4OP and 4NP were detected only in T. blochii at concentrations of 0.084ng/g and 0.078ng/g, respectively. The results of the present study provide insights on monitoring and managing mariculture activity in relation to environmental protection and food safety. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Concentrations of selected pharmaceuticals and antibiotics in south-central Pennsylvania waters, March through September 2006

    Science.gov (United States)

    Loper, Connie A.; Crawford, J. Kent; Otto, Kim L.; Manning, Rhonda L.; Meyer, Michael T.; Furlong, Edward T.

    2007-01-01

    This report presents environmental and quality-control data from analyses of 15 pharmaceutical and 31 antibiotic compounds in water samples from streams and wells in south-central Pennsylvania. The analyses are part of a study by the U.S. Geological Survey (USGS) in cooperation with the Pennsylvania Department of Environmental Protection (PADEP) to define concentrations of selected emerging contaminants in streams and well water in Pennsylvania. Sampling was conducted at 11 stream sites and at 6 wells in 9 counties of south-central Pennsylvania. Five of the streams received municipal wastewater and 6 of the streams received runoff from agricultural areas dominated by animal-feeding operations. For all 11 streams, samples were collected at locations upstream and downstream of the municipal effluents or animal-feeding operations. All six wells were in agricultural settings. A total of 120 environmental samples and 21 quality-control samples were analyzed for the study. Samples were collected at each site in March/April, May, July, and September 2006 to obtain information on changes in concentration that could be related to seasonal use of compounds.For streams, 13 pharmaceuticals and 11 antibiotics were detected at least 1 time. Detections included analytical results that were estimated or above the minimum reporting limits. Seventy-eight percent of all detections were analyzed in samples collected downstream from municipal-wastewater effluents. For streams receiving wastewater effluents, the pharmaceuticals caffeine and para-xanthine (a degradation product of caffeine) had the greatest concentrations, 4.75 μg/L (micrograms per liter) and 0.853 μg/L, respectively. Other pharmaceuticals and their respective maximum concentrations were carbamazepine (0.516 μg/L) and ibuprofen (0.277 μg/L). For streams receiving wastewater effluents, the antibiotic azithromycin had the greatest concentration (1.65 μg/L), followed by sulfamethoxazole (1.34 μg/L), ofloxacin (0.329

  14. Process for selectively concentrating the radioactivity of thorium containing magnesium slag

    International Nuclear Information System (INIS)

    Wilson, D.A.; Christiansen, S.H.; Simon, J.; Morin, D.W.

    1993-01-01

    In a process for separating magnesium from a magnesium slag using water and carbon dioxide, the improvement described comprises: (a) forming an aqueous magnesium slurry from the magnesium slag, which slag contains radioactive thorium and its daughters, and water; (b) solubilizing magnesium from the magnesium slurry by reacting the aqueous magnesium slurry with carbon dioxide wherein the carbon dioxide is at a pressure from greater than ambient to about 1,000 psig (about 7,000 kPa); (c) selectively concentrating by filtering the radioactive thorium and its daughters such that the radioactive thorium and its daughters are separated from the solubilized magnesium filtrate; and (d) reducing volume and/or weight of radioactive solids for disposal as radioactive waste

  15. Novel selective and potent 5-HT reuptake inhibitors with 5-HT1D antagonist activity: chemistry and pharmacological evaluation of a series of thienopyran derivatives.

    Science.gov (United States)

    Torrado, Alicia; Lamas, Carlos; Agejas, Javier; Jiménez, Alma; Diaz, Nuria; Gilmore, Jeremy; Boot, John; Findlay, Jeremy; Hayhurst, Lorna; Wallace, Louise; Broadmore, Richard; Tomlinson, Rosemarie

    2004-10-15

    A series of compounds combining the naphthylpiperazine and thienopyran scaffolds has been prepared and evaluated for 5-HT reuptake inhibition with 5-HT1D antagonist activity. The design of these compounds has been based on the 'overlapping type' strategy where two pharmacophores are linked in a single molecule. The resultant dual pharmacological profile has the potential to deliver a more efficient treatment for depression.

  16. Comparative study of radon concentration in selected modern and traditional building at Kenyatta University

    International Nuclear Information System (INIS)

    Chege, W.M.; Rathore, I.V.S.; Chhabra, S.C.; Mustapha, A.O.

    2010-01-01

    Radon is leading source of radiation exposure to the public and increases risk of cancer (UNSCEAR, 2000). There is general lack of data on indoor radon in Kenya especially on building design-traditional versus modern. In rural Kenya traditional mud huts coexist with modern stone building. Indoor radon found to vary widely in Kenya: Mustapha et al (2002): 5-1200 Bqm3, Maina et al (2004): 5-704 Bqm3. None of previous works indicates radon variation with building design. The aim of the current study is to compare radon concentrations in coexisting stone buildings and mud huts. Such data would be useful in formulation of policies regarding housing, as part of radon data base in Kenya Experimental Techniques Characteristic of selected buildings: Traditional Huts: Single roomed, Wall made of wood and plastered using mud, bare floor and no ceiling, grass-thatched or mud plastered, doors and windows remained open during the sampling period. Modern Buildings: (Classes used to represent modern building). Those made of natural stone, wooden floor, ceiling, doors and windows remained shut during the sampling period. Measurement of Radon Concentration Radon sampling was done using Charcoal canisters (EPA type). They were activated, and then exposed simultaneously at sampling sites for 48 hours. Analysis and data acquisition was done using NaI(Tl) gamma-ray spectrometer. Radon concentration was calculated based on gamma rays emitted by 214Pb (295 and 352 keV) and 214Bi (609 keV). 13 Results and Discussion Radon levels were higher in classrooms and significantly high in huts. Mean (Bqm-3 ) Minimum (Bqm-3 ) Maximum (Bqm-3 ). Traditional huts had 170.3 15.6 30.2 315.4 while modern buildings had 193 ±19.3 115.76 257.2. There were higher levels in classroom despite lower levels of 226Ra (50.18 Bqkg-1) in natural stone. Possible source of high concentrations: - radon seeping in through floor boards building up over time as building more closed up - Radon concentration was more varied

  17. Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses.

    Science.gov (United States)

    Knych, H K; Steinmetz, S J; McKemie, D S

    2015-04-01

    The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L for the central and peripheral compartments, respectively. Terminal elimination half-life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative-like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent. © 2014 John Wiley & Sons Ltd.

  18. Systemic tobramycin concentrations during selective decontamination of the digestive tract in intensive care unit patients on continuous venovenous hemofiltration

    NARCIS (Netherlands)

    Mol, Meriel; van Kan, H. J. M.; Schultz, Marcus J.; de Jonge, Evert

    2008-01-01

    OBJECTIVE: To study whether selective decontamination of the digestive tract (SDD) results in detectable serum tobramycin concentrations in intensive care unit (ICU) patients with acute renal failure treated with continuous venovenous hemofiltration (CVVH). DESIGN AND SETTING: Prospective,

  19. Effects of Apple Juice Concentrate, Blackcurrant Concentrate and Pectin Levels on Selected Qualities of Apple-Blackcurrant Fruit Leather

    Directory of Open Access Journals (Sweden)

    Lemuel M. Diamante

    2013-09-01

    Full Text Available A study was conducted to determine the effects of different levels of apple juice concentrate (AJC, blackcurrant concentrate (BCC and pectin on the moisture content, water activity, color, texture and ascorbic acid content of apple-blackcurrant fruit leather using the response surface methodology. The results showed the moisture content increased with increasing pectin level and with greater increases at higher AJC and BCC levels while the water activity increased with increasing pectin level and with increasing AJC level, at low pectin levels, but with decreasing AJC, at high pectin levels. The chroma decreased with increasing pectin level and with lower values at the middle AJC level. The puncturing force decreased with increasing AJC level but with a lower value at the middle pectin level. Lastly, the ascorbic acid content increased with increasing BCC level regardless of AJC and pectin levels. There is a need to reduce the drying temperature or time of apple-blackcurrant fruit leather just enough to bring the water activity closer to 0.60, thereby increasing the moisture content resulting in higher product yield.

  20. Effects of Apple Juice Concentrate, Blackcurrant Concentrate and Pectin Levels on Selected Qualities of Apple-Blackcurrant Fruit Leather.

    Science.gov (United States)

    Diamante, Lemuel M; Li, Siwei; Xu, Qianqian; Busch, Janette

    2013-09-12

    A study was conducted to determine the effects of different levels of apple juice concentrate (AJC), blackcurrant concentrate (BCC) and pectin on the moisture content, water activity, color, texture and ascorbic acid content of apple-blackcurrant fruit leather using the response surface methodology. The results showed the moisture content increased with increasing pectin level and with greater increases at higher AJC and BCC levels while the water activity increased with increasing pectin level and with increasing AJC level, at low pectin levels, but with decreasing AJC, at high pectin levels. The chroma decreased with increasing pectin level and with lower values at the middle AJC level. The puncturing force decreased with increasing AJC level but with a lower value at the middle pectin level. Lastly, the ascorbic acid content increased with increasing BCC level regardless of AJC and pectin levels. There is a need to reduce the drying temperature or time of apple-blackcurrant fruit leather just enough to bring the water activity closer to 0.60, thereby increasing the moisture content resulting in higher product yield.

  1. Elevated CO2 and O3t concentrations differentially affect selected groups of the fauna in temperate forest soils

    Science.gov (United States)

    Gladys I. Loranger; Kurt S. Pregitzer; John S. King

    2004-01-01

    Rising atmospheric CO2 concentrations may change soil fauna abundance. How increase of tropospheric ozone (O3t) concentration will modify these responses is still unknown. We have assessed independent and interactive effects of elevated [CO2] and [O3t] on selected groups of soil...

  2. Determination of the Influence of Substrate Concentration on Enzyme Selectivity Using Whey Protein Isolate and Bacillus licheniformis Protease

    NARCIS (Netherlands)

    Butré, C.I.; Sforza, S.; Gruppen, H.; Wierenga, P.A.

    2014-01-01

    Increasing substrate concentration during enzymatic protein hydrolysis results in a decrease in hydrolysis rate. To test if changes in the mechanism of hydrolysis also occur, the enzyme selectivity was determined. The selectivity is defined quantitatively as the relative rate of hydrolysis of each

  3. Concentration of ions in selected bottled water samples sold in Malaysia

    Science.gov (United States)

    Aris, Ahmad Zaharin; Kam, Ryan Chuan Yang; Lim, Ai Phing; Praveena, Sarva Mangala

    2013-03-01

    Many consumers around the world, including Malaysians, have turned to bottled water as their main source of drinking water. The aim of this study is to determine the physical and chemical properties of bottled water samples sold in Selangor, Malaysia. A total of 20 bottled water brands consisting of `natural mineral (NM)' and `packaged drinking (PD)' types were randomly collected and analyzed for their physical-chemical characteristics: hydrogen ion concentration (pH), electrical conductivity (EC) and total dissolved solids (TDS), selected major ions: calcium (Ca), potassium (K), magnesium (Mg) and sodium (Na), and minor trace constituents: copper (Cu) and zinc (Zn) to ascertain their suitability for human consumption. The results obtained were compared with guideline values recommended by World Health Organization (WHO) and Malaysian Ministry of Health (MMOH), respectively. It was found that all bottled water samples were in accordance with the guidelines set by WHO and MMOH except for one sample (D3) which was below the pH limit of 6.5. Both NM and PD bottled water were dominated by Na + K > Ca > Mg. Low values for EC and TDS in the bottled water samples showed that water was deficient in essential elements, likely an indication that these were removed by water treatment. Minerals like major ions were present in very low concentrations which could pose a risk to individuals who consume this water on a regular basis. Generally, the overall quality of the supplied bottled water was in accordance to standards and guidelines set by WHO and MMOH and safe for consumption.

  4. Concentric-Electrode Organic Electrochemical Transistors: Case Study for Selective Hydrazine Sensing

    Directory of Open Access Journals (Sweden)

    Sébastien Pecqueur

    2017-03-01

    Full Text Available We report on hydrazine-sensing organic electrochemical transistors (OECTs with a design consisting of concentric annular electrodes. The design engineering of these OECTs was motivated by the great potential of using OECT sensing arrays in fields such as bioelectronics. In this work, poly(3,4-ethylenedioxythiophene:poly(styrenesulfonate (PEDOT:PSS-based OECTs have been studied as aqueous sensors that are specifically sensitive to the lethal hydrazine molecule. These amperometric sensors have many relevant features for the development of hydrazine sensors, such as a sensitivity down to 10−5 M of hydrazine in water, an order of magnitude higher selectivity for hydrazine than for nine other water-soluble common analytes, the capability to entirely recover its base signal after water flushing, and a very low operation voltage. The specificity for hydrazine to be sensed by our OECTs is caused by its catalytic oxidation at the gate electrode, and enables an increase in the output current modulation of the devices. This has permitted the device-geometry study of the whole series of 80 micrometric OECT devices with sub-20-nm PEDOT:PSS layers, channel lengths down to 1 µm, and a specific device geometry of coplanar and concentric electrodes. The numerous geometries unravel new aspects of the OECT mechanisms governing the electrochemical sensing behaviours of the device—more particularly the effect of the contacts which are inherent at the micro-scale. By lowering the device cross-talk, micrometric gate-integrated radial OECTs shall contribute to the diminishing of the readout invasiveness and therefore further promote the development of OECT biosensors.

  5. Rate and selectivity modification in Fischer-Tropsch synthesis over charcoal supported molybdenum by forced concentration cycling

    International Nuclear Information System (INIS)

    Dun, J.W.; Gulari, E.

    1985-01-01

    Forced concentration cycling of the feed between pure CO and pure H/sub 2/ was used to successfully change both the selectivities and reactivities of promoted and unpromoted charcoal supported molybdenum catalysts in Fischer-Tropsch synthesis. It was found that with the unpromoted catalyst the rate enhancement increases with temperature and selectivity shifts towards methane. At the lower temperatures concentration cycling increases selectivity to ethane and higher hydrocarbons to levels only achievable with promised catalysts. Periodic operation with the potassium promoted catalyst results in small rate enhancements but the olefin to paraffin ratio is dramatically changed without changing the carbon number distribution

  6. Selective effects of whey protein concentrate on glutathione levels and apoptosis in rats with mammary tumors.

    Science.gov (United States)

    Cheng, Shih-Hsuan; Tseng, Yang-Ming; Wu, Szu-Hsien; Tsai, Shih-Meng; Tsai, Li-Yu

    2017-09-01

    Glutathione (GSH) plays an important role in antioxidant defense and regulation of apoptosis. GSH deficiency is related to many diseases, including cancer, and increased GSH levels in cancer cells are associated with chemotherapy resistance because of resistance to apoptosis. In this study, we investigated the effects of whey protein concentrate (WPC), a precursor of GSH, in rats with mammary tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA). DMBA treatment results in cellular changes that mimic the initiation and promotion of carcinogenesis of breast tissue. We aimed to examine the possible preventive effects of diets containing whey protein on DMBA-induced mammary tumors in rats. The results indicate that WPC (0.334 g/kg) supplementation significantly increased the liver GSH levels by 92%, and were accompanied by low Bax/Bcl-2 ratio (from 5 to 3) and cleaved caspase-3/procaspase-3 ratio (from 2.4 to 1.2) in DMBA-treated rats. Furthermore, tumor GSH levels were decreased by 47% in WPC-supplemented rats, which resulted in increased Bax/Bcl-2 ratio (from 0.9 to 2) and cleaved caspase-3/procaspase-3 ratio (from 1.1 to 2.7). In conclusion, supplementation with WPC could selectively deplete tumor GSH levels and, therefore, WPC supplementation might be a promising strategy to overcome treatment resistance in cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. CEMS Investigations of Fe-Silicide Phases Formed by the Method of Concentration Controlled Phase Selection

    Energy Technology Data Exchange (ETDEWEB)

    Moodley, M. K.; Bharuth-Ram, K. [University of Durban-Westville, Physics Department (South Africa); Waal, H. de; Pretorius, R. [University of Stellenbosch, Physics Department (South Africa)

    2002-03-15

    Conversion electron Moessbauer spectroscopy (CEMS) measurements have been made on Fe-silicide samples formed using the method of concentration controlled phase selection. To prepare the samples a 10 nm layer of Fe{sub 30}M{sub 70} (M=Cr, Ni) was evaporated onto Si(100) surfaces, followed by evaporation of a 60 nm Fe layer. Diffusion of the Fe into the Si substrate and the formation of different Fe-Si phases was achieved by subjecting the evaporated samples to a series of heating stages, which consisted of (a) a 10 min anneal at 800 deg. C plus etch of the residual surface layer, (b) a further 3 hr anneal at 800 deg. C, (c) a 60 mJ excimer laser anneal to an energy density of 0.8 J/cm{sup 2}, and (d) a final 3 hr anneal at 800 deg. C. CEMS measurements were used to track the Fe-silicide phases formed. The CEMS spectra consisted of doublets which, based on established hyperfine parameters, could be assigned to {alpha}- or {beta}-FeSi{sub 2} or cubic FeSi. The spectra showed that {beta}-FeSi{sub 2} had formed already at the first annealing stage. Excimer laser annealing resulted in the formation of a phase with hyperfine parameters consistent with those of {alpha}-FeSi{sub 2}. A further 3 hr anneal at 800 deg. C resulted in complete reversal to the semiconducting {beta}-FeSi{sub 2} phase.

  8. Selective Media for Actinide Collection and Pre-Concentration: Results of FY 2006 Studies

    Energy Technology Data Exchange (ETDEWEB)

    Lumetta, Gregg J.; Addleman, Raymond S.; Hay, Benjamin P.; Hubler, Timothy L.; Levitskaia, Tatiana G.; Sinkov, Sergey I.; Snow, Lanee A.; Warner, Marvin G.; Latesky, Stanley L.

    2006-11-17

    In this work, we have investigated new materials for potential use in automated radiochemical separations. The work can be divided into three primary tasks: (1) synthesis of new ligands with high affinity for actinide ions, (2) evaluation of new materials for actinide ion affinity, and (3) computational design of advanced ligand architectures for highly selective binding of actinide ions. Ligand Synthesis Work was conducted on synthesizing Kl?ui ligand derivatives containing functionalized pendant groups on the cyclopentadienyl ring. The functionalized pendent groups would allow these ligands to be attached to organic and inorganic solid supports. This work focused on synthesizing the compound Na[Cp?Co(PO(OC2H5)2)3], where Cp?= C5H4C(O)OCH3. Synthesizing this compound is feasible, but the method used in FY 2006 produced an impure material. A modified synthetic scheme has been developed and will be pursued in FY 2007. Work was also initiated on synthesizing bicyclic diamides functionalized for binding to polymeric resins or other surfaces. Researchers at the University of Oregon are collaborators in this work. To date, this effort has focused on synthesizing and characterizing a symmetrically substituted bicyclic diamide ligand with the ?COOH functionality. Again, this synthetic effort will continue into FY 2007. Separations Material Evaluation Work was conducted in FY 2006 to provide a more extensive set of data on the selectivity and affinity of extraction chromatography resins prepared by sorption of Kl?ui ligand onto an inert macroreticular polymeric support. Consistent with previous observations, it was found that these materials strongly bind tetravalent actinides. These materials also adsorb trivalent actinides at low nitric acid concentrations, but the affinity for the trivalent actinides decreases with increasing nitric acid concentration. These materials have relatively low affinity for U(VI), but they do sorb U(VI) to a greater extent than Am(III) at [HNO

  9. Selective Media for Actinide Collection and Pre-Concentration: Results of FY 2006 Studies

    International Nuclear Information System (INIS)

    Lumetta, Gregg J.; Addleman, Raymond S.; Hay, Benjamin P.; Hubler, Timothy L.; Levitskaia, Tatiana G.; Sinkov, Sergey I.; Snow, Lanee A.; Warner, Marvin G.; Latesky, Stanley L.

    2006-01-01

    In this work, we have investigated new materials for potential use in automated radiochemical separations. The work can be divided into three primary tasks: (1) synthesis of new ligands with high affinity for actinide ions, (2) evaluation of new materials for actinide ion affinity, and (3) computational design of advanced ligand architectures for highly selective binding of actinide ions. Ligand Synthesis Work was conducted on synthesizing Kl?ui ligand derivatives containing functionalized pendant groups on the cyclopentadienyl ring. The functionalized pendent groups would allow these ligands to be attached to organic and inorganic solid supports. This work focused on synthesizing the compound Na[Cp?Co(PO(OC2H5)2)3], where Cp?C5H4C(O)OCH3. Synthesizing this compound is feasible, but the method used in FY 2006 produced an impure material. A modified synthetic scheme has been developed and will be pursued in FY 2007. Work was also initiated on synthesizing bicyclic diamides functionalized for binding to polymeric resins or other surfaces. Researchers at the University of Oregon are collaborators in this work. To date, this effort has focused on synthesizing and characterizing a symmetrically substituted bicyclic diamide ligand with the ?COOH functionality. Again, this synthetic effort will continue into FY 2007. Separations Material Evaluation Work was conducted in FY 2006 to provide a more extensive set of data on the selectivity and affinity of extraction chromatography resins prepared by sorption of Kl?ui ligand onto an inert macroreticular polymeric support. Consistent with previous observations, it was found that these materials strongly bind tetravalent actinides. These materials also adsorb trivalent actinides at low nitric acid concentrations, but the affinity for the trivalent actinides decreases with increasing nitric acid concentration. These materials have relatively low affinity for U(VI), but they do sorb U(VI) to a greater extent than Am(III) at [HNO3

  10. Trace element concentration and speciation in selected urban soils in New York City.

    Science.gov (United States)

    Burt, R; Hernandez, L; Shaw, R; Tunstead, R; Ferguson, R; Peaslee, S

    2014-01-01

    A long history of urbanization and industrialization has affected trace elements in New York City (NYC) soils. Selected NYC pedons were analyzed by aqua regia microwave digestion and sequential chemical extraction as follows: water soluble (WS); exchangeable (EX); specifically sorbed/carbonate bound (SS/CAR); oxide-bound (OX); organic/sulfide bound (OM/S). Soils showed a range in properties (e.g., pH 3.9 to 7.4). Sum of total extractable (SUMTE) trace elements was higher in NYC parks compared to Bronx River watershed sites. NYC surface horizons showed higher total extractable (TE) levels compared to US non-anthropogenic soils. TE levels increased over 10 year in some of the relatively undisturbed and mostly wooded park sites. Surface horizons of park sites with long-term anthropogenic inputs showed elevated TE levels vs. subsurface horizons. Conversely, some Bronx River watershed soils showed increased concentrations with depth, reflective of their formation in a thick mantle of construction debris increasing with depth and intermingled with anthrotransported soil materials. Short-range variability was evident in primary pedons and satellite samples (e.g., Pb 253 ± 143 mg/kg). Long-range variability was indicated by PbTE (348 versus 156 mg/kg) and HgTE (1 versus 0.3 mg/kg) concentrations varying several-fold in the same soil but in different geographic locations. Relative predominance of fractions: RES (37 %) > SS/CAR (22 %) > OX (20 %) > OM/S (10 %) > EX (7 %) > WS (4 %). WS and EX fractions were greatest for Hg (7 %) and Cd (14 %), respectively. RES was predominant fraction for Co, Cr, Ni, and Zn (41 to 51 %); SS/CAR for Cd and Pb (40 and 63 %); OM/S for Cu and Hg (36 and 37 %); and OX for As (59 %).

  11. Comparative study of the selective degradations of two enantiomers in the racemate and an enriched concentration of indoxacarb in soils.

    Science.gov (United States)

    Zhang, Yu-Ping; Hu, De-Yu; Ling, Hu-Rong; Zhong, Lei; Huang, An-Xiang; Zhang, Kan-Kan; Song, Bao-An

    2014-09-17

    In this study, selective degradations of the two enantiomers of indoxacarb in the concentrate (2.33S/1R) and racemate (1S/1R) are examined. The absolute configurations of indoxacarb enantiomers were determined using X-ray diffraction. The results showed that in two alkaline soils, the S-(+)-indoxacarb was preferentially degraded in both the concentrate and racemate. In one acid soil, the two enantiomers degraded no-selectivity. In another acid soil and one neutral soil, the R-(-)-indoxacarb was preferentially degraded in both the concentrate and racemate. Indoxacarb enantiomers were configurationally stable in the five soils, and no interconversion was observed during the incubation. Because no significant difference in degradation was observed after samples were sterilized, the observed enantioselectivity may be attributed primarily to microbial activity in soils. The results indicate that the selective degradation behavior was the same for both formulations that were tested.

  12. Temperature Programmed Desorption of Quench-condensed Krypton and Acetone in Air; Selective Concentration of Ultra-trace Gas Components.

    Science.gov (United States)

    Suzuki, Taku T; Sakaguchi, Isao

    2016-01-01

    Selective concentration of ultra-trace components in air-like gases has an important application in analyzing volatile organic compounds in the gas. In the present study, we examined quench-condensation of the sample gas on a ZnO substrate below 50 K followed by temperature programmed desorption (TPD) (low temperature TPD) as a selective gas concentration technique. We studied two specific gases in the normal air; krypton as an inert gas and acetone as a reactive gas. We evaluated the relationship between the operating condition of low temperature TPD and the lowest detection limit. In the case of krypton, we observed the selective concentration by exposing at 6 K followed by thermal desorption at about 60 K. On the other hand, no selectivity appeared for acetone although trace acetone was successfully concentrated. This is likely due to the solvent effect by a major component in the air, which is suggested to be water. We suggest that pre-condensation to remove the water component may improve the selectivity in the trace acetone analysis by low temperature TPD.

  13. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

    Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

  14. Pharmacology of a selective cyclooxygenase-2 inhibitor, HN-56249: a novel compound exhibiting a marked preference for the human enzyme in intact cells.

    Science.gov (United States)

    Berg, J; Fellier, H; Christoph, T; Kremminger, P; Hartmann, M; Blaschke, H; Rovensky, F; Towart, R; Stimmeder, D

    2000-04-01

    HN-56249 (3-(2,4-dichlorothiophenoxy)-4-methylsulfonylamino-benzenesu lfonamide), a highly selective cyclooxygenase (COX)-2 inhibitor, is the prototype of a novel series of COX inhibitors comprising bicyclic arylethersulfonamides; of this series HN-56249 is the most potent and selective human COX-2 inhibitor. HN-56249 inhibited platelet aggregation as a measure of COX-1 activity only moderately (IC50 26.5+/-1.7 microM). In LPS-stimulated monocytic cells the release of prostaglandin (PG) F1alpha as a measure of COX-2 was markedly inhibited (IC50 0.027+/-0.001 microM). Thus, HN-56249 showed an approximately 1000-fold selectivity for COX-2 in intact cells. In whole blood assays HN-56249 showed a potent inhibitory activity for COX-2 (IC50 0.78+/-0.37 microM) only. COX-1 was only weakly inhibited (IC50 867+/-181 microM). Hence, HN-56249 exhibited a greater than 1000-fold selectivity for whole blood COX-2. HN-56249 surpassed the COX-2 selectivities of the COX-2 selective inhibitors 3-cyclohexyloxy-4-methylsulfonylamino-nitrobenzene (NS-398) and 6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanone (flosulide) in the intact cell assays by eight- and threefold, respectively, and in the whole blood assays by approximately 40-fold. Following i.v. administration HN-56249 inhibited carrageenan-induced rat paw oedema only moderately (ID50 26.2+/-5.7 mg/kg, mean +/- SEM), approximately tenfold less potent than indomethacin (ID50 2.1+/-0.2 mg/kg, mean +/- SEM). After oral administration HN-56249 reversed thermal hyperalgesia in the carrageenan-induced rat paw oedema test, however, some 30-fold less potently than diclofenac. Comparing the inhibitory potency of HN-56249 against human COX-2 with that against murine COX-2 in intact cells revealed a 300-fold selectivity for the human enzyme. Similar effects were observed with other COX-2-selective arylethersulfonamides. In contrast, non-COX-2-selective arylethersulfonamides, including a highly selective COX-1 inhibitor, inhibited

  15. Optimization research on the concentration field of NO in selective catalytic reduction flue gas denitration system

    Science.gov (United States)

    Zheng, Qingyu; Zhang, Guoqiang; Che, Kai; Shao, Shikuan; Li, Yanfei

    2017-08-01

    Taking 660 MW generator unit denitration system as a study object, an optimization and adjustment method shall be designed to control ammonia slip, i.e. adjust ammonia injection system based on NO concentration distribution at inlet/outlet of the denitration system to make the injected ammonia distribute evenly. The results shows that, this method can effectively improve NO concentration distribution at outlet of the denitration system and decrease ammonia injection amount and ammonia slip concentration. Reduce adverse impact of SCR denitration process on the air preheater to realize safe production by guaranteeing that NO discharge shall reach the standard.

  16. Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens

    DEFF Research Database (Denmark)

    Nassan, Feiby L; Coull, Brent A; Gaskins, Audrey J

    2017-01-01

    : In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004-2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change...... PCP use and concentrations of the other phthalate metabolites were not statistically significant. CONCLUSIONS: We identified 10 PCPs of relevance and demonstrated that their use within 6 h of urine collection strongly predicted MEP and paraben urinary concentrations. https://doi.org/10.1289/EHP1374....

  17. Rotating night shift work, sleep quality, selected lifestyle factors and prolactin concentration in nurses and midwives.

    Science.gov (United States)

    Bukowska, Agnieszka; Sobala, Wojciech; Peplonska, Beata

    2015-04-01

    The pattern of secretion of many hormones, including prolactin, is dependent on the circadian rhythm. Night shift work involves exposure to artificial light at night and sleep deficiency, which in turn can affect prolactin synthesis. The aim of this study was to evaluate a possible association between night shift work characteristics, sleep quality, lifestyle factors and prolactin concentration, using data from a cross-sectional study of nurses and midwives. A cross-sectional study was conducted among 327 nurses and midwives currently working on rotating night shifts, and 330 nurses and midwives working during the day (aged 40-60 years) (388 premenopausal and 269 postmenopausal). Information about night shift work characteristics, lifestyle, reproductive factors, sleep pattern and other covariates was collected through a face-to-face interview, and from a one-week work and sleep diary completed by the subjects. Weight and height were measured. Prolactin concentration was measured in the morning blood sample using the electrochemiluminesence immunoassay method. Associations were analyzed using linear regression models adjusted for important confounders. Analyses were carried out separately in pre- and postmenopausal women. None of the night shift work or sleep characteristics was significantly associated with prolactin concentration. Prolactin concentration was significantly (p night shift work is not associated with prolactin concentration. Smoking, parity, time of blood collection and age among postmenopausal women were significant determinants of prolactin.

  18. Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian R; Andersen, Kim

    2002-01-01

    Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro...

  19. Pharmacological characterization of potent and selective NaV1.7 inhibitors engineered from Chilobrachys jingzhao tarantula venom peptide JzTx-V.

    Directory of Open Access Journals (Sweden)

    Bryan D Moyer

    Full Text Available Identification of voltage-gated sodium channel NaV1.7 inhibitors for chronic pain therapeutic development is an area of vigorous pursuit. In an effort to identify more potent leads compared to our previously reported GpTx-1 peptide series, electrophysiology screening of fractionated tarantula venom discovered the NaV1.7 inhibitory peptide JzTx-V from the Chinese earth tiger tarantula Chilobrachys jingzhao. The parent peptide displayed nominal selectivity over the skeletal muscle NaV1.4 channel. Attribute-based positional scan analoging identified a key Ile28Glu mutation that improved NaV1.4 selectivity over 100-fold, and further optimization yielded the potent and selective peptide leads AM-8145 and AM-0422. NMR analyses revealed that the Ile28Glu substitution changed peptide conformation, pointing to a structural rationale for the selectivity gains. AM-8145 and AM-0422 as well as GpTx-1 and HwTx-IV competed for ProTx-II binding in HEK293 cells expressing human NaV1.7, suggesting that these NaV1.7 inhibitory peptides interact with a similar binding site. AM-8145 potently blocked native tetrodotoxin-sensitive (TTX-S channels in mouse dorsal root ganglia (DRG neurons, exhibited 30- to 120-fold selectivity over other human TTX-S channels and exhibited over 1,000-fold selectivity over other human tetrodotoxin-resistant (TTX-R channels. Leveraging NaV1.7-NaV1.5 chimeras containing various voltage-sensor and pore regions, AM-8145 mapped to the second voltage-sensor domain of NaV1.7. AM-0422, but not the inactive peptide analog AM-8374, dose-dependently blocked capsaicin-induced DRG neuron action potential firing using a multi-electrode array readout and mechanically-induced C-fiber spiking in a saphenous skin-nerve preparation. Collectively, AM-8145 and AM-0422 represent potent, new engineered NaV1.7 inhibitory peptides derived from the JzTx-V scaffold with improved NaV selectivity and biological activity in blocking action potential firing in both

  20. Determination of the minimum inhibitory concentration (MIC and mutant prevention concentration (MPC of selected antimicrobials in bovine and swine Pasteurella multocida, Escherichia coli, and Staphylococcus aureus isolates

    Directory of Open Access Journals (Sweden)

    Kateřina Nedbalcová

    2015-01-01

    Full Text Available We compared the values of the minimum inhibitory concentration (MIC and mutant prevention concentration (MPC values ​​of three antimicrobial agents for 72 bovine isolates of Pasteurella multocida, 80 swine isolates of P. multocida, 80 bovine isolates of Escherichia coli, 80 swine isolates of E. coli, and 80 isolates of Staphylococcus aureus from bovine mastitis. The ratio of MIC90​​/MPC90 which limited mutant selection window (MSW was ≤ 0.12/4 mg/l for enrofloxacin, 0.5/≥ 64 mg/l for florfenicol and 4/≥ 128 mg/l for tulathromycin in bovine P. multocida isolates, ≤ 0.12/2 mg/l for enrofloxacin, 0.5/≥ 64 mg/l for florfenicol and 4/≥ 128 mg/l for tulathromycin in swine P. multocida isolates, 1/16 mg/l for enrofloxacin, 8/≥ 64 mg/l for florfenicol and 8/≥ 128 mg/l for tulathromycin in bovine E. coli isolates, 0.5/16 mg/l for enrofloxacin, ≥ 64/≥ 64 mg/l for florfenicol and 8/≥ 128 mg/l for tulathromycin in swine E. coli isolates, and 0.25/16 mg/l for enrofloxacin, 4/≥ 64 mg/l for florfenicol and 4/≥ 128 mg/l for tulathromycin in S. aureus isolates. These findings indicate that the dosage of antimicrobial agents to achieve serum concentration equal to or higher than MPC could reduce selection of resistant bacterial subpopulation.

  1. Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens

    DEFF Research Database (Denmark)

    Nassan, Feiby L; Coull, Brent A; Gaskins, Audrey J

    2017-01-01

    BACKGROUND: Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men's exposure is understudied. OBJECTIVES: We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. METHODS...... in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use. RESULTS: Four hundred men contributed 1,037 urine samples (mean of 3/man...

  2. Activity concentration and AACED due to 40K in some selected medicinal plants

    International Nuclear Information System (INIS)

    Chandrashekara, K.; Radhakrishna, A.P.; Somashekarappa, H.M.

    2017-01-01

    The activity concentrations in soil and medicinal plants, soil to plant transfer factors (TF), and Average Annual Committed Effective Dose (AACED) of 40 K in prominent medicinal plants of Malnad Kerala were estimated. The range of activity concentrations were 144.15 - 558.99 and 405.87 - 2990.75 Bq kg -1 in soil and medicinal plants respectively. The TF was found to vary from 2.34 to 14.84, whereas AACED varied in the range 2.51 - 18.54 mSv y -1 . The study may help to form the database and safety regulations connected with 40 K activity in medicinal plants. (author)

  3. Biological and Pharmacological properties

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Biological and Pharmacological properties. NOEA inhibits Ceramidase. Anandamide inhibits gap junction conductance and reduces sperm fertilizing capacity. Endogenous ligands for Cannabinoid receptors (anandamide and NPEA). Antibacterial and antiviral ...

  4. Systemic tobramycin concentrations during selective decontamination of the digestive tract in intensive care unit patients on continuous venovenous hemofiltration.

    Science.gov (United States)

    Mol, Meriel; van Kan, Hendrikus J M; Schultz, Marcus J; de Jonge, Evert

    2008-05-01

    To study whether selective decontamination of the digestive tract (SDD) results in detectable serum tobramycin concentrations in intensive care unit (ICU) patients with acute renal failure treated with continuous venovenous hemofiltration (CVVH). Prospective, observational, single-center study in a mixed medical-surgical ICU. Adult ICU patients receiving SDD for at least 3 days and being treated with CVVH because of acute renal failure. Tobramycin serum concentrations were measured at the 3rd day after start of CVVH and every 3 days thereafter. Detectable serum concentrations of tobramycin were found in 12 (63%) of 19 patients and in 15 (58%) of the 26 samples. With a toxic tobramycin concentration defined as more than 2.0 mg/l, we found one patient with a toxic concentration of 3.0 mg/l. In three other patients tobramycin concentrations of >or=1.0 mg/l were found. In patients with acute renal failure treated with CVVH, administration of SDD with tobramycin can lead to detectable and potentially toxic serum tobramycin concentrations.

  5. Novel procedure for the extraction and concentration of carotenoid-containing chromoplasts from selected plant systems.

    Science.gov (United States)

    Fish, Wayne W

    2007-02-21

    Natural sources of carotenoids for nutraceutical use are desired by the food industry as a result of the increased production of convenience and other highly processed foods. As new physiological roles are discovered for some of the minor carotenoids that are found in only small amounts in present sources, the need for discovery of new sources will amplify. Thus, a method is needed that will effectively and gently concentrate carotenoids from potential new sources for subsequent identification and analysis. A procedure is presented by which carotenoid-containing tissue chromoplasts can be extracted and subsequently concentrated by precipitation, all in an aqueous milieu. The chromoplasts are extracted and solubilized with 0.3% sodium dodecyl sulfate (SDS) in water. The addition of a nominally equal volume of acetonitrile to the chromoplasts in SDS immediately precipitates the chromoplasts out of solution with generally >90% recovery. Carotenoids contained in the concentrated, still-intact chromoplasts can then be solubilized by organic solvent extraction for subsequent analysis. This methodology offers a means to effectively and gently concentrate carotenoids from fruit tissues where yields are often low (e.g., yellow watermelon).

  6. Concentration factors and aggregated transfer factors in selected bio-indicators from Sweden[Radioecology

    Energy Technology Data Exchange (ETDEWEB)

    Holm, E.; Samuelsson, C.; Holstensson, M. [Lund Univ. (Sweden)

    2006-04-15

    Previously most common has been to use lichens and mosses in the terrestrial environment and mussels and algae in the marine environment. Several plants are promising and less commonly used such as ferns (e.g. Bracken, Pteridium aquilinum) and the fresh water plant, Water horsetail (Equisetum fluviatile). These show high uptake of radiocaesium but also accumulate plutonium and americium. Even if the uptake of transuranic elements is low, this behaviour is rather unique for plants. On bases of available data we have calculated concentration factors Cf and aggregated transfer factors, ATF according to their definitions i.e. Bq kg{sup -1} (biota)/Bq kg{sup -1}(water) and Bq kg{sup -1} (biota)/Bq m{sup -2} respectively. For earlier samples the water concentrations can only roughly be estimated while deposition data are rather well known. For fresh water samples it is a little awkward to use concentration factors since the uptake generally is not from water. Therefore a kind of Aggregated Transfer Factor has also been calculated on basis of using the same areal deposition in sediments as on land. We have used dry weight concentrations for biota. Data are presented for samples of various bio-medicator organisms. (LN)

  7. Petroleum hydrocarbon concentration in selected species of fish and prawn form northwest coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Mehta, P.; Kadam, A.N.; Gajbhiye, S.N.; Desai, B.N.

    of the method was in he range of 36.9-78.5% for 1-10 mu g.g/1, wet wt chrysene concentrations. The levels observed were low ranging from 0.2 to 10.0 mu g.g/1 (wet wt, chrysene equivalent units). The most abundant species Johnius glaucus and Coilia dussumieri...

  8. Radioactivity concentration variation with depth and assessment of workers' doses in selected mining sites

    Directory of Open Access Journals (Sweden)

    C.U. Nwankwo

    2015-04-01

    Full Text Available Mining workers are exposed to radiation in the process of extracting minerals from the earth crust. In this research, activity concentration of the radionuclides in samples collected at different depths in Komu (0–220 ft and Olode (0–30 ft mining sites, Oyo State, Nigeria and the associated workers' radiological risks were assessed. Gemstones from these sites are mined for local and international markets. The radionuclide contents of the samples were determined using Gamma spectroscopy technique. At Komu, 238U and 232Th concentrations, with few exceptions, increased with depth while that of 40K had no defined pattern. At Olode site, 238U and 232Th concentrations decreased with depth while that of 40K was almost constant. Internal hazard indices at Komu in some cases indicated an unacceptable level of risk to workers. Workers' doses would have been underestimated by between 12 and 55% if the activity concentrations of samples in the pit were not included in the calculation.

  9. [Concentration of selected angiogenic factors in serum and peritoneal fluid of women with endometriosis].

    Science.gov (United States)

    Gogacz, Marek; Gałczyński, Krzysztof; Romanek-Piva, Katarzyna; Winkler, Izabela; Rechberger, Tomasz; Adamiak-Godlewska, Aneta

    2015-03-01

    Endometriosis is a sex hormone-dependent and successively progressing gynecological disease, characterized by the presence of endometrial tissue outside the uterus. The etiology of endometriosis is known to be multifactorial, and its growth depends on immunological, hormonal, genetic and environmental factors. Angiogenesis plays a key role in implantation and growth of endometriotic lesions, as well as in adhesion formation. Physiologically angiogenesis is responsible for neoangiogenesis and recruitment of new capillaries from the already existing capillaries. It is well-documented that altered angiogenesis provokes improper follicular maturation, infertility recurrent miscarriages, ovarian hyperstimulation syndrome, and carcinogenesis. Factors stimulating angionesis include angiogenin, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). The aim of the study was to analyze angiogenic factor concentration (angiogenin, VEGF, FGF) in blood serum and peritoneal fluid in patients with diagnosed endometriosis and idiopathic infertility. A total of 39 patients were recruited for the study including 19 patients (study group) diagnosed with endometriosis during the laparoscopic procedure and 20 patients (control group) with idiopathic infertility and no morphologic changes within the pelvis revealed during the laparoscopic procedure. All patients underwent laparoscopy during the follicular phase of the menstrual cycle. Vein blood sample was obtained before the procedure and during laparoscopy the entire peritoneal fluid was aspirated for further measurement of VEGF, FGF and angiogenin concentrations. Angiogenin concentration in peritoneal fluid was statistically higher in patient with idiopathic infertility in comparison to endometriosis (pendometriosis, but no statistical significance was found. VEGF and FGF concentration in blood serum and peritoneal fluid was similar in both groups (p>0.05). There were no significant differences between serum

  10. Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

  11. Compilation of 137Cs concentrations at selected sites in the continental United States

    International Nuclear Information System (INIS)

    Mohr, R.A.; Franks, L.A.

    1982-01-01

    This report summarizes results of cesium-137 analyses of soil samples obtained at 21 locations throughout the continental United States. The sites were all in the vicinity of operating nuclear power reactors, or those scheduled for operation. Selected fallout and meteorological data are also included

  12. Identification and concentration of selected pesticide residues in Ghanaian cocoa beans

    International Nuclear Information System (INIS)

    Sefakor, Adzo Fialor

    2017-07-01

    Pest and disease have been the major causes of low cocoa production worldwide and the use of chemicals in the form of pesticides is one of the main ways of mitigating their undesirable outcome. However, inappropriate application of pesticides does not only affect the quality of cocoa bean products and the well being of consumers of such products but can also damage the natural flora and fauna in the environment. Hence the reason why evaluating the concentrations of pesticide residues is necessary in establishing the quality of a cocoa. The goal of this study was therefore to determine the concentrations and distribution of specific pesticide residues in cocoa beans from the six cocoa growing regions of Ghana. Three classes of pesticides were tested for in cocoa beans obtained from seventeen (17) districts in the Brong Ahafo, Eastern, Central, Western North, Ashanti and Western South cocoa growing regions of Ghana. These were the neonicotinoids (Thiamethoxam, Clothianidin, Imidacloprid and Acetamiprid); the synthetic pyrethroids (Cypermethrin, Deltamethrin, Fenvalerate, Lambda Cyhalothrin and Permethrin) and the organophosphorous compound Chlorpyrifos. Pesticide residue analyses were done separately on the whole unshelled beans, the nibs and the shells using a GC/ECD for the synthetic pyrethroids and organophosphorous compound and a QqQ-LC/MS for the neonicotinoids. The results obtained showed that the mean concentrations of the neonicotinoids in all the three matrices ranged from <0.001 to 0.018 mg/kg in the shells, <0.001 to 0.0025 mg/kg in the nibs and <0.001 to 0.005 mg/kg in the whole beans with Imidacloprid being the predominant one. Ashanti Region had the highest concentration of Imidacloprid in all the three matrices whilst Eastern Region recorded the least concentration of Imidacloprid in the shells (0.009 mg/kg) and whole unshelled beans (0.002 mg/kg). In relations to the synthetic pyrethroids tested for, the results obtained indicated that out of the

  13. Iron concentrations in breast milk and selected maternal factors of human milk bank donors.

    Science.gov (United States)

    Mello-Neto, Julio; Rondó, Patrícia H C; Morgano, Marcelo A; Oshiiwa, Marie; Santos, Mariana L; Oliveira, Julicristie M

    2010-05-01

    The aim of this study was to evaluate the relationship between iron concentration in mature breast milk and characteristics of 136 donors of a Brazilian milk bank. Iron, vitamin A, zinc, and copper concentrations were assessed in human milk and maternal blood. Data were collected on maternal anthropometrics, obstetric, socioeconomic, demographic, and lifestyle factors. Iron, zinc, and copper in milk and zinc and copper in blood were detected by spectrophotometry. Vitamin A in milk and blood was determined by high-performance liquid chromatography. Hemoglobin was measured by electronic counting and serum iron and ferritin by colorimetry and chemoluminescence, respectively. Transferrin and ceruloplasmin were determined by nephelometry. According to multivariate linear regression analysis, iron in milk was positively associated with vitamin A in milk and with smoking but negatively associated with timing of breast milk donation (P milk of Brazilian donors may be influenced by nutritional factors and smoking.

  14. Genomic copy concentrations of selected waterborne viruses in a slum environment in Kampala, Uganda.

    Science.gov (United States)

    Katukiza, A Y; Temanu, H; Chung, J W; Foppen, J W A; Lens, P N L

    2013-06-01

    The presence of viruses in a slum environment where sanitation is poor is a major concern. However, little is known of their occurrence and genomic copy concentration in the slum environment. The main objective of this study was to determine the genomic copy concentrations of human adenoviruses F and G, Rotavirus (RV), Hepatitis A virus (HAV), Hepatitis E virus (HEV) and human adenovirus species A,C,D,E, and F (HAdV-ACDEF) in Bwaise III, a typical slum in Kampala, Uganda. Forty-one samples from surface water, grey water and ground water were collected from 30 sampling locations. The virus particles were recovered by glass wool filtration with elution using beef extract. DNA and RNA viruses were detected by the real time quantitative polymerase chain reaction (qPCR) and the reverse transcription-qPCR (RT-qPCR), respectively. HAdV-F and G were detected in 70.7% of the samples with concentrations up to 2.65 × 10(1) genomic copies per mL (gc mL(-1)). RV and HAV were detected in 60.9% and 17.1% of the samples, respectively. The maximum concentration of RV was 1.87 × 10(2)gc mL(-1). In addition, 78% of the samples tested positive for the HAdV-ACDEF, but all samples tested negative for HEV. These new data are essential for quantitative microbial risk assessment, and for understanding the effects of environmental pollution in slums.

  15. Effects of seasons on the concentration of selected trace elements in horse hair

    Directory of Open Access Journals (Sweden)

    Jadwiga TOPCZEWSKA

    2012-12-01

    Full Text Available The studies were conducted on a group of 20 mares of the Hucul breed kept in free range system. The horses made use of pastures in summer periods while being fed with hay or silage during the winter. Mares that bore offspring regularly, in good conditions and healthy were involved in the analysis. Hair samples of about 500 mg were taken from areas around the neck under the mane of each horse four times a year. The concentration of 6 elements, i.e., B, Ni, Si, Mo, I and Cr were measured in each sample. Much higher concentrations of molybdenum and nickel were found in hair samples collected in spring, but more of boron in autumn while those from winter contained more of chromium, silicon and iodine. The concentration of all the analyzed minerals differed significantly in relation to the season. A significant positive relationship between levels of nickel and molybdenum on the one hand as well as between silicon and chromium on the other was demonstrated. A negative correlation was, however, observed between the levels of iodine and molybdenum as well as between iodine and nickel.

  16. Selective removal of U(VI) from low concentration wastewater by functionalized HKUST-1@H3PW12O40

    International Nuclear Information System (INIS)

    Hui Zhang; Jinhua Xue; Nan Hu; Jing Sun; Dexin Ding; Yongdong Wang; Le Li

    2016-01-01

    The adsorption of U(VI) from low concentration solution by HKUST-1@H 3 PW 12 O 40 was studied as a function of various experimental parameters including pH, interfering ions, contact time, initial uranium concentration and temperature by batch experiments. Equilibrium data were found to fit with Langmuir isotherm model better than Freundlich isotherm model. The kinetic adsorption was fitted by the pseudo-second-order model well. Thermodynamic data from the adsorption experiments indicate that adsorption process is spontaneous and endothermic. HKUST-1@H 3 PW 12 O 40 can selectively adsorb U(VI) from multi-metal ion solutions and the adsorption capacity of HKUST-1@H 3 PW 12 O 40 don't decrease significantly after three cycles of desorption-reuse. The results show that HKUST-1@H 3 PW 12 O 40 is suitable for removal of U(VI) from low concentration solutions. (author)

  17. Impact of low-energy CT imaging on selection of positive oral contrast media concentration.

    Science.gov (United States)

    Patino, Manuel; Murcia, Diana J; Iamurri, Andrea Prochowski; Kambadakone, Avinash R; Hahn, Peter F; Sahani, Dushyant V

    2017-05-01

    To determine to what extent low-energy CT imaging affects attenuation of gastrointestinal tract (GIT) opacified with positive oral contrast media (OCM). Second, to establish optimal OCM concentrations for low-energy diagnostic CT exams. One hundred patients (38 men and 62 women; age 62 ± 11 years; BMI 26 ± 5) with positive OCM-enhanced 120-kVp single-energy CT (SECT), and follow-up 100-kVp acquisitions (group A; n = 50), or 40-70-keV reconstructions from rapid kV switching-single-source dual-energy CT (ssDECT) (group B; n = 50) were included. Luminal attenuation from different GIT segments was compared between exams. Standard dose of three OCM and diluted solutions (75%, 50%, and 25% concentrations) were introduced serially in a gastrointestinal phantom and scanned using SECT (120, 100, and 80 kVp) and DECT (80/140 kVp) acquisitions on a ssDECT scanner. Luminal attenuation was obtained on SECT and DECT images (40-70 keV), and compared to 120-kVp scans with standard OCM concentrations. Luminal attenuation was higher on 100-kVp (328 HU) and on 40-60-keV images (410-924 HU) in comparison to 120-kVp scans (298 HU) in groups A and B (p < 0.05). Phantom: There was an inverse correlation between luminal attenuation and X-ray energy, increasing up to 527 HU on low-kVp and 999 HU on low-keV images (p < 0.05). 25% and 50% diluted OCM solutions provided similar or higher attenuation than 120 kVp, at low kVp and keV, respectively. Low-energy CT imaging increases the attenuation of GIT opacified with positive OCM, permitting reduction of 25%-75% OCM concentration.

  18. Hydrogen evolution activity and electrochemical stability of selected transition metal carbides in concentrated phosphoric acid

    DEFF Research Database (Denmark)

    Tomás García, Antonio Luis; Jensen, Jens Oluf; Bjerrum, Niels J.

    2014-01-01

    phosphoric acid were investigated in a temperature range from 80 to 170°C. A significant dependence of the activities on temperature was observed for all five carbide samples. Through the entire temperature range Group 6 metal carbides showed higher activity than that of the Group 5 metal carbides......Alternative catalysts based on carbides of Group 5 (niobium and tantalum) and 6 (chromium, molybdenum and tungsten) metals were prepared as films on the metallic substrates. The electrochemical activities of these carbide electrodes towards the hydrogen evolution reaction (HER) in concentrated...

  19. Effect of Exposure to Hyperoxic, Hypobaric, and Hyperbaric Environments on Concentrations of Selected Aerobic and Anaerobic Fecal Flora of Mice

    Science.gov (United States)

    Gillmore, James D.; Gordon, Francis B.

    1975-01-01

    Alterations in selected aerobic and anaerobic fecal microflora of the mouse were determined during exposure to hyperoxic and normoxic hypo- and hyperbaric environments. Examination of fecal cultures obtained during exposure for 6 weeks to either 60 or 77% oxygen concentration at 1 atmosphere absolute revealed little alteration in the aerobic or anaerobic flora. There appeared to be only a retardation in the reduction of the Klebsiella-Enterobacter flora which normally occurs after weaning. During exposure to hypobaric environments (100% O2, 0.2 atmosphere absolute), significant alterations in concentrations of Escherichia coli, slow lactose fermenters, Klebsiella-Enterobacter, and enterococci were found in some instances. All alterations were toward increased concentrations. Variations in concentrations of different colony types of obligately anaerobic gram-positive (anGPR) and gram-negative (anGNR) rods cultured during the same experiments also occurred. One colony type of anGPR appeared to decrease while a second type increased in numbers. Concentrations of three colony types of anGNR were generally, but not always, increased. During hyperbaric exposure (2.8% O2, 7.5 atmospheres absolute), increased concentrations of Klebsiella-Enterobacter, E. coli, slow lactose fermenters and enterococci were also noted. Changes in numbers of both colony types of anGPR, when occurring, were in the direction of lower numbers. Alteration in numbers of anGNR were in both directions but were more frequent in the direction of higher numbers. After return to normal air for 4 weeks of either hypo- or hyperbaric exposure, fecal concentrations of all organisms tended to revert toward control values with the exception of the anGPR which remained in lower concentrations after termination of the hyperbaric exposure. These observations indicate that, despite the great variation in the fecal flora among individual mice, it is possible to discover the effects induced by altered gaseous

  20. Rational design, synthesis, and pharmacological properties of new 1,8-naphthyridin-2(1H)-on-3-carboxamide derivatives as highly selective cannabinoid-2 receptor agonists

    DEFF Research Database (Denmark)

    Manera, Clementina; Saccomanni, Giuseppe; Adinolfi, Barbara

    2009-01-01

    The CB(2) receptor activation can be exploited for the treatment of diseases such as chronic pain and tumors of immune origin, devoid of psychotropic activity. On the basis of our already reported 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives, new 1,8-naphthyridin-2(1H)-on-3-carboxamide......-dependent decrease of cell viability. The obtained results suggest that 1,8-naphthyridin-2(1H)-on-3-carboxamides represent a new scaffold very suitable for the development of new promising CB(2) agonists....... derivatives were designed, synthesized, and tested for their affinities toward the human CB(1) and CB(2) cannabinoid receptors. Some of the reported compounds showed a subnanomolar CB(2) affinity with a CB(1)/CB(2) selectivity ratio greater than 200 (compounds 6, 12, cis-12, 13, and cis-13). Further studies...

  1. Concentrations and solubility of selected trace metals in leaf and bagged black teas commercialized in Poland

    Directory of Open Access Journals (Sweden)

    L. Polechońska

    2015-09-01

    Full Text Available The objective of this study was to determine the concentrations of heavy metals in bagged and leaf black teas of the same brand and evaluate the percentage transfer of metals to tea infusion to assess the consumer exposure. Ten leaf black teas and 10 bagged black teas of the same brand available in Poland were analyzed for Zn, Mn, Cd, Pb, Ni, Co, Cr, Al, and Fe concentrations both in dry material and their infusion. The bagged teas contained higher amounts of Pb, Mn, Fe, Ni, Al, and Cr compared with leaf teas of the same brand, whereas the infusions of bagged tea contained higher levels of Mn, Ni, Al, and Cr compared with leaf tea infusions. Generally, the most abundant trace metals in both types of tea were Al and Mn. There was a wide variation in percentage transfer of elements from the dry tea materials to the infusions. The solubility of Ni and Mn was the highest, whereas Fe was insoluble and only a small portion of this metal content may leach into infusion. With respect to the acceptable daily intake of metals, the infusions of both bagged and leaf teas analyzed were found to be safe for human consumption.

  2. Ozone concentrations at a selected high-elevation forest site downwind Mexico City

    Science.gov (United States)

    Torres-JArdon, R.

    2013-05-01

    Torres-Jardón, R.*, Rosas-Pérez, I., Granada-Macías, L. M., Ruiz-Suárez, L. G. Centro de Ciencias de la Atmósfera, UNAM, México D. F. México * rtorres@unam.mx For many years, the vegetation of forest species such as Abies religiosa in natural parks located in the southwest mountains of Mexico City has attracted much attention since these parks have been experiencing a severe decline of unclear etiology. The high ozone levels in the area and the observed naked eye macroscopic, histological and cytological injuries on these species, strongly suggest an important contribution of tropospheric ozone to this deterioration process. Apart of historical short monitoring campaigns for measuring ozone levels in these mountains, it is known just a little is known about the present exposure levels at which the local vegetation is exposed. A continuous ozone analyzer has been in operation since 2011 at a high-elevation forest site (Parque Nacional Miguel Hidalgo, PNMH; 3110 m above mean sea level) located downwind of Mexico City Metropolitan Area (MCMA), in order to characterize the local ozone diel amplitude and its seasonal trend, as well as the influence of MCMA on the local O3 concentrations. Hourly average ozone data in PNMH shows that in general, the diel of ozone concentrations in the forest site has a statistical significant correlation with the pattern of ozone levels observed in several monitoring sites (smog receptor sites) within the MCMA, although the high elevation O3 levels are relatively lower than those in the urban area (around 2200 m above mean sea level). It is possible that a part of the oxidants in the air masses are removed by sink deposition processes during the air mass transport across the hills. The diel amplitude of ozone concentrations is small in the cold season, increasing as the seasons advance to June. As in the city, the highest ozone concentrations occur in April or May and the lowest levels during the rainy season, which extends from

  3. Perinatal pharmacology: applications for neonatal neurology.

    Science.gov (United States)

    Smits, Anne; Allegaert, Karel

    2011-11-01

    The principles of clinical pharmacology also apply to neonates, but their characteristics warrant a tailored approach. We focus on aspects of both developmental pharmacokinetics (concentration/time relationship) and developmental pharmacodynamics (concentration/effect relationship) in neonates. We hereby aimed to link concepts used in clinical pharmacology with compound-specific observations (anti-epileptics, analgosedatives) in the field of neonatal neurology. Although in part anecdotal, we subsequently illustrate the relevance of developmental pharmacology in the field of neonatal neurology by a specific intervention (e.g. whole body cooling), specific clinical presentations (e.g. short and long term outcome following fetal exposure to antidepressive agents, the development of new biomarkers for fetal alcohol syndrome) and specific clinical needs (e.g. analgosedation in neonates, excitocytosis versus neuro-apoptosis/impaired synaptogenesis). Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  4. Identification and in vitro pharmacological characterization of a novel and selective α7 nicotinic acetylcholine receptor agonist, Br-IQ17B.

    Science.gov (United States)

    Tang, Jing-shu; Xie, Bing-xue; Bian, Xi-ling; Xue, Yu; Wei, Ning-ning; Zhou, Jing-heng; Hao, Yu-chen; Li, Gang; Zhang, Liang-ren; Wang, Ke-wei

    2015-07-01

    Alpha7-nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated Ca(2+)-permeable ion channel implicated in cognition and neuropsychiatric disorders. Activation of α7 nAChR improves learning, memory, and sensory gating in animal models. To identify novel α7 nAChR agonists, we synthesized a series of small molecules and characterized a representative compound, Br-IQ17B, N-[(3R)-1-azabicyclo[2,2,2]oct-3-yl]-5-bromoindolizine-2-carboxamide, which specifically activates α7 nAChR. Two-electrode voltage clamp (TEVC) recordings were primarily used for screening in Xenopus oocytes expressing human α7 nAChR. Assays, including radioisotope ligand binding, Western blots, whole-cell recordings of hippocampal culture neurons, and spontaneous IPSC recordings of brain slices, were also utilized to evaluate and confirm the specific activation of α7 nAChR by Br-IQ17B. Br-IQ17B potently activates α7 nAChR with an EC50 of 1.8±0.2 μmol/L. Br-IQ17B is selective over other subtypes such as α4β2 and α3β4, but it blocks 5-HT3A receptors. Br-IQ17B displaced binding of the α7 blocker [(3)H]-MLA to hippocampal crude membranes with a Ki of 14.9±3.2 nmol/L. In hippocampal neurons, Br-IQ17B evoked α7-like currents that were inhibited by MLA and enhanced in the presence of the α7 PAM PNU-120596. In brain slice recordings, Br-IQ17B enhanced GABAergic synaptic transmission in CA1 neurons. Mechanistically, Br-IQ17B increased ERK1/2 phosphorylation that was MLA-sensitive. We identified the novel, potent, and selective α7 agonist Br-IQ17B, which enhances synaptic transmission. Br-IQ17B may be a helpful tool to understand new aspects of α7 nAChR function, and it also has potential for being developed as therapy for schizophrenia and cognitive deficits.

  5. Selectivity improvement of positive photoionization ion mobility spectrometry for rapid detection of organophosphorus pesticides by switching dopant concentration.

    Science.gov (United States)

    Zhou, Qinghua; Li, Jia; Wang, Bin; Wang, Shuang; Li, Haiyang; Chen, Jinyuan

    2018-01-01

    Ion mobility spectrometry (IMS) opened a potential avenue for the rapid detection of organophosphorus pesticides (OPPs), though an improved selectivity of stand-alone IMS was still in high demand. In this study, a stand-alone positive photoionization ion mobility spectrometry (PP-IMS) apparatus was constructed for the rapid detection of OPPs with acetone as dopant. The photoionization of acetone molecules was induced by the ultraviolet irradiation to produce the reactant ions (Ac) 2 H + , which were employed to ionize the OPPs including fenthion, imidan, phosphamidon, dursban, dimethoate and isocarbophos via the proton transfer reaction. Due to the difference in proton affinity, the tested OPPs exhibited the different dopant-dependent manners. Based on this observation, the switching of dopant concentration was implemented to improve the selectivity of PP-IMS for OPPs detection. For instance, a mixture of fenthion, dursban and dimethoate was tested. By switching the concentration of doped acetone from 0.07 to 2.33 to 19.94mgL -1 , the ion peaks of fenthion and dursban were inhibited in succession, achieving the selective detection of dimethoate at last. In addition, another mixture of imidan and phosphamidon was initially detected by PP-IMS with a dose of 0.07mgL -1 acetone, indicating that their ion peaks were severely overlapped; when the concentration of doped acetone was switched to 19.94mgL -1 , the inhibition of imidan signals promised the accurate identification of phosphamidon in mixture. Finally, the PP-IMS in combination of switching dopant concentration was applied to detect the mixed fenthion, dursban and dimethoate in Chinese cabbage, demonstrating the applicability of proposed method to real samples. Copyright © 2017. Published by Elsevier B.V.

  6. CONCENTRATION OF SELECTED ELEMENTS IN RAW AND ULTRA HEAT TREATED COW MILK

    Directory of Open Access Journals (Sweden)

    Lukáčová Anetta

    2012-10-01

    Full Text Available The potential presence of toxic metals in food is being recognized as a priority by standards organizations and constitutes an analytical challenge. The toxic metal content of milk and dairy products is due to several factors: environmental conditions, the manufacturing process and the possible contamination during several steps of the manufacturing processes. The aim of this study was to evaluate samples of raw milk with fat contents 3.8% obtained at randomly from animal farms in around Nitra, western Slovakia region and ultra – heat treated cow milk (UHT with fat contents 1.5% commercially available from local market in Nitra. Samples of milk were analysed for metal contents using atomic absorption spectrophotometry (AAS. UHT milk showed higher levels of cadmium, nickel and iron. Higher levels of zinc, copper were detected in raw milk. Significant differences in the concentration of copper between raw and UHT cow milk were found.

  7. The effect of increased ozone concentrations in the air on selected aspects of rat reproduction.

    Science.gov (United States)

    Jedlińska-Krakowska, M; Gizejewski, Z; Dietrich, G J; Jakubowski, K; Glogowski, J; Penkowski, A

    2006-01-01

    Five-month-old male rates were exposed to 0.5 ppm ozone for 50 days, 5 hours a day. A week before the completion of ozone exposure, a biological test was performed to determine the fertilization rate and the survival rate of newborns in both ozone-exposed and control animals. After 50 days, the rats were sacrificed with an overdose of halotane, and testes were collected to assess the morphology and motility of spermatozoa. Neither the morphology of spermatozoa nor motility parameters determined by the CASA (computer-assisted sperm analysis) system showed statistically significant differences between ozone-exposed and control males. The number of successful matings and the survival rate of newborns per litter within one year postpartum were also similar in both groups. However, sperm concentration was by 17% lower in ozone-exposed rats, compared with the control animals.

  8. Tangential flow ultrafiltration: a "green" method for the size selection and concentration of colloidal silver nanoparticles.

    Science.gov (United States)

    Anders, Catherine B; Baker, Joshua D; Stahler, Adam C; Williams, Austin J; Sisco, Jackie N; Trefry, John C; Wooley, Dawn P; Pavel Sizemore, Ioana E

    2012-10-04

    Nowadays, AgNPs are extensively used in the manufacture of consumer products,(1) water disinfectants,(2) therapeutics,(1, 3) and biomedical devices(4) due to their powerful antimicrobial properties.(3-6) These nanoparticle applications are strongly influenced by the AgNP size and aggregation state. Many challenges exist in the controlled fabrication(7) and size-based isolation(4,8) of unfunctionalized, homogenous AgNPs that are free from chemically aggressive capping/stabilizing agents or organic solvents.(7-13) Limitations emerge from the toxicity of reagents, high costs or reduced efficiency of the AgNP synthesis or isolation methods (e.g., centrifugation, size-dependent solubility, size-exclusion chromatography, etc.).(10,14-18) To overcome this, we recently showed that TFU permits greater control over the size, concentration and aggregation state of Creighton AgNPs (300 ml of 15.3 μg ml(-1) down to 10 ml of 198.7 μg ml(-1)) than conventional methods of isolation such as ultracentrifugation.(19) TFU is a recirculation method commonly used for the weight-based isolation of proteins, viruses and cells.(20,21) Briefly, the liquid sample is passed through a series of hollow fiber membranes with pore size ranging from 1,000 kD to 10 kD. Smaller suspended or dissolved constituents in the sample will pass through the porous barrier together with the solvent (filtrate), while the larger constituents are retained (retentate). TFU may be considered a "green" method as it neither damages the sample nor requires additional solvent to eliminate toxic excess reagents and byproducts. Furthermore, TFU may be applied to a large variety of nanoparticles as both hydrophobic and hydrophilic filters are available. The two main objectives of this study were: 1) to illustrate the experimental aspects of the TFU approach through an invited video experience and 2) to demonstrate the feasibility of the TFU method for larger volumes of colloidal nanoparticles and smaller volumes of

  9. Measuring concentrations of selected air pollutants inside California vehicles. Final report

    International Nuclear Information System (INIS)

    Rodes, C.; Sheldon, L.; Whitaker, D.; Clayton, A.; Fitzgerald, K.

    1999-01-01

    This project measured 2-hour integrated concentrations of PM10, PM2.5, metals and a number of organic chemicals including benzene and MTBE inside vehicles on California roadways. Using continuous samplers, particle counts, black carbon, and CO were also measured. In addition to measuring in-vehicle levels, the investigators measured pollutant levels just outside the vehicle, at roadside stations, and ambient air monitoring stations. Different driving scenarios were designed to assess the effects of a number of factors on in-vehicle pollutant levels. These factors included roadway type, carpool lanes, traffic conditions, geographical locations, vehicle type, and vehicle ventilation conditions. The statewide average in-vehicle concentrations of benzene, MTBE, and formaldehyde ranged from 3--22 microg/m 3 , 3--90 microg/m 3 , and 0---22 microg/m 3 , respectively. The ranges of mean PM10 and PM2.5 in-vehicle levels in Sacramento were 20--40 microg/m 3 and 6--22 microg/m 3 , respectively. In general, pollutant levels inside or just outside the vehicles were higher than those measured at the roadside stations or the ambient air stations. In-vehicle pollutant levels were consistently higher in Los Angeles than Sacramento. Pollutant levels measured inside vehicles traveling in a carpool lane were much lower than those in the right-hand, slower lanes. Under the study conditions, factors such as vehicle type and ventilation and little effect on in-vehicle pollutant levels. Other factors, such as roadway type, freeway congestion level, and time-of-day had some influence on in-vehicle pollution levels

  10. Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma

    Directory of Open Access Journals (Sweden)

    Jolanta Budzyńska-Włodarczyk

    2016-02-01

    Full Text Available Introduction : Localized scleroderma is an autoimmune disease primarily affecting the skin. The cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components. Aim: To determine concentrations of interleukin (IL-27, transforming growth factor (TGF-β1, TGF-β2, IL-6, and sIL-6R in patients with localized scleroderma compared to controls and to assess the relations between their levels and laboratory markers. Material and methods: The study encompassed 17 females with localized scleroderma (aged 25–67. The control group consisted of 30 age-matched healthy women. The blood was sampled from the basilic vein. Serum levels of cytokines were determined using ELISA. Results : The TGF-β2 levels were found to be significantly lower in patients with localized scleroderma compared to controls. Concentrations of TGF-β1 were decreased in scleroderma patients when compared to controls but without statistical significance. There were no significant differences in serum IL-6, sIL-6R and IL-27 levels between patients and the control group; however, we found a significant positive correlation between the level of sIL-6 and ESR among subjects with localized scleroderma. Conclusions : The findings of decreased serum levels of TGF-β1 and TGF-β2 in patients with localized scleroderma demonstrate a possible association of these cytokines with pathogenesis of the disease. The results suggest also that sIL-6R is likely to be involved in inflammation in patients with localized scleroderma.

  11. Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma.

    Science.gov (United States)

    Budzyńska-Włodarczyk, Jolanta; Michalska-Jakubus, Małgorzata M; Kowal, Małgorzata; Krasowska, Dorota

    2016-02-01

    Localized scleroderma is an autoimmune disease primarily affecting the skin. The cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components. To determine concentrations of interleukin (IL)-27, transforming growth factor (TGF)-β1, TGF-β2, IL-6, and sIL-6R in patients with localized scleroderma compared to controls and to assess the relations between their levels and laboratory markers. The study encompassed 17 females with localized scleroderma (aged 25-67). The control group consisted of 30 age-matched healthy women. The blood was sampled from the basilic vein. Serum levels of cytokines were determined using ELISA. The TGF-β2 levels were found to be significantly lower in patients with localized scleroderma compared to controls. Concentrations of TGF-β1 were decreased in scleroderma patients when compared to controls but without statistical significance. There were no significant differences in serum IL-6, sIL-6R and IL-27 levels between patients and the control group; however, we found a significant positive correlation between the level of sIL-6 and ESR among subjects with localized scleroderma. The findings of decreased serum levels of TGF-β1 and TGF-β2 in patients with localized scleroderma demonstrate a possible association of these cytokines with pathogenesis of the disease. The results suggest also that sIL-6R is likely to be involved in inflammation in patients with localized scleroderma.

  12. Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.

    Directory of Open Access Journals (Sweden)

    Shanmiao Gou

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133⁺ but not CD24⁺CD44⁺ESA⁺ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133⁺ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease.

  13. Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline.

    Science.gov (United States)

    Gjestad, Caroline; Westin, Andreas A; Skogvoll, Eirik; Spigset, Olav

    2015-02-01

    The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline. Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs. Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered.

  14. Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

    Directory of Open Access Journals (Sweden)

    Andrzej Prystupa

    2016-06-01

    Full Text Available According to the WHO report, alcohol is the third most significant health risk factor for the global population. There are contrary reports about heavy metals concentrations in patients with alcoholic liver cirrhosis. The aim of this study was to investigate serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis living in the eastern part of Poland according to cirrhosis stage. The participants came from various hospitals of the Lublin region were enrolled. The study group included 46 male and 16 female patients. The control group consisted of 18 healthy individuals without liver disease. High Performance Ion Chromatography was used to determine the concentrations of metal ions (Cd, Zn, Cu, Ni, Co, Mn, and Pb in serum samples. The concentrations of copper, zinc, nickel, and cobalt were found to be significantly lower in patients with alcoholic liver cirrhosis compared to the control group. The serum concentration of cadmium was significantly higher in patients with advanced alcoholic liver cirrhosis compared to the control group. We hypothesize that disorders of metabolism of heavy metals seem to be the outcome of impaired digestion and absorption, which are common in cirrhosis, improper diet, environmental and occupational exposure.

  15. Highly Localized Acoustic Streaming and Size-Selective Submicrometer Particle Concentration Using High Frequency Microscale Focused Acoustic Fields.

    Science.gov (United States)

    Collins, David J; Ma, Zhichao; Ai, Ye

    2016-05-17

    Concentration and separation of particles and biological specimens are fundamental functions of micro/nanofluidic systems. Acoustic streaming is an effective and biocompatible way to create rapid microscale fluid motion and induce particle capture, though the >100 MHz frequencies required to directly generate acoustic body forces on the microscale have traditionally been difficult to generate and localize in a way that is amenable to efficient generation of streaming. Moreover, acoustic, hydrodynamic, and electrical forces as typically applied have difficulty manipulating specimens in the submicrometer regime. In this work, we introduce highly focused traveling surface acoustic waves (SAW) at high frequencies between 193 and 636 MHz for efficient and highly localized production of acoustic streaming vortices on microfluidic length scales. Concentration occurs via a novel mechanism, whereby the combined acoustic radiation and streaming field results in size-selective aggregation in fluid streamlines in the vicinity of a high-amplitude acoustic beam, as opposed to previous acoustic radiation induced particle concentration where objects typically migrate toward minimum pressure locations. Though the acoustic streaming is induced by a traveling wave, we are able to manipulate particles an order of magnitude smaller than possible using the traveling wave force alone. We experimentally and theoretically examine the range of particle sizes that can be captured in fluid streamlines using this technique, with rapid particle concentration demonstrated down to 300 nm diameters. We also demonstrate that locations of trapping and concentration are size-dependent, which is attributed to the combined effects of the acoustic streaming and acoustic forces.

  16. Low Concentrations of Metformin Selectively Inhibit CD133+ Cell Proliferation in Pancreatic Cancer and Have Anticancer Action

    Science.gov (United States)

    Li, Xiangsheng; Shi, Pengfei; Liu, Tao; Wang, Chunyou

    2013-01-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133+ but not CD24+CD44+ESA+ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133+ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease. PMID:23667692

  17. Selected Trace Element Concentrations in Peat Used for Cosmetic Production – A Case Study from Southern Poland

    Directory of Open Access Journals (Sweden)

    Glina Bartłomiej

    2016-12-01

    Full Text Available The aim of the study was to assess the concentration of selected trace elements in organic soils used as a source to obtain a unique peat extract for cosmetics production. Peat material for laboratory analysis were collected from fen peatland located in the Prosna River Valley (Borek village. Studied peatland is managed by “Torf Corporation” company as a source of material to obtain peat extract for cosmetics production. In the collected soil samples (four soil profiles Zn, Cu and Pb concentrations were determined by using atomic absorption spectrometer SpectraAA 220 (Varian, after acid digestion. Obtained results showed that the highest concentrations of selected trace elements were recorded in the surface horizons of organic soils. This fact might be the results of Prosna river flooding or air deposition. Howevere, according to the new Polish regulations (Ordinance of the Minister for Environment 01.09.2016 - the way of conducting contamination assessment of the earth surface, the content of trace elements in the examined soils was greatly belowe the permissible limit for areas from group IV (mine lands. Thus, described soils are proper to obtain peat extract used as a component in cosmetic production.

  18. The Impact of Carrot Enriched in Iodine through Soil Fertilization on Iodine Concentration and Selected Biochemical Parameters in Wistar Rats

    Science.gov (United States)

    Piątkowska, Ewa; Kopeć, Aneta; Bieżanowska-Kopeć, Renata; Pysz, Mirosław; Kapusta-Duch, Joanna; Koronowicz, Aneta Agnieszka; Smoleń, Sylwester; Skoczylas, Łukasz; Ledwożyw-Smoleń, Iwona; Rakoczy, Roksana; Maślak, Edyta

    2016-01-01

    Iodine is one of the trace elements which are essential for mammalian life. The major objective of iodine biofortification of plants is to obtain food rich in this trace element, which may increase its consumption by various populations. Additionally, it may reduce the risk of iodine deficiency diseases. In this research for the first time we have assessed the bioavailability of iodine from raw or cooked carrot biofortified with this trace element on iodine concentration in selected tissues and various biochemical parameters as well as mRNA expression of some genes involved in iodine metabolism in Wistar rats. Statistically, a significantly higher iodine level was determined in urine, faeces and selected tissues of rats fed a diet containing biofortified raw carrot as compared to a diet without iodine and a diet containing control cooked carrot. Biofortified raw carrot significantly increased triiodothyronine concentration as compared to animals from other experimental groups. The highest thyroid stimulating hormone level was determined in rats fed control cooked carrots. mRNA expression of selected genes was affected by different dietary treatment in rats’ hearts. Biofortified raw and cooked carrot could be taken into account as a potential source of iodine in daily diets to prevent iodine deficiency in various populations. PMID:27043135

  19. Literature review of the concentration ratios of selected radionuclides in freshwater and marine fish

    Energy Technology Data Exchange (ETDEWEB)

    Poston, T.M.; Klopfer, D.C.

    1986-09-01

    Concentration ratios (CR's) used for modeling the uptake and food chain transport of radionuclides in fish have usually been conservative; that is, at the high end of reported values. This practice ensures that the dose to the consumer of contaminated fish will not be underestimated. In many models, however, conservative values have been used for all variables that have any uncertainty associated with them. As a result the dose to the consumer is overestimated. Realistic CR values need to be developed to establish model parameters that will accurately reflect tissue burdens in fish and resulting dose rates to consumers. This report reviews and summarizes published literature on the uptake and distribution of stable and radioactive isotopes of 26 elements. Based on this review, we have made recommendations on CR values to be used for modeling the accumulation of radionuclides in fish. Our recommendations are compared with CR values reported in other publications. A generic discussion of abiotic and biotic factors that influence CR values is provided so that CR values may be adjusted based on site-specific characteristics of the fishes habitat. Recommended CR values for freshwater fish and for marine fish are listed. Although this report emphasizes radionuclides, it is applicable to stable elements as well.

  20. Literature review of the concentration ratios of selected radionuclides in freshwater and marine fish

    International Nuclear Information System (INIS)

    Poston, T.M.; Klopfer, D.C.

    1986-09-01

    Concentration ratios (CR's) used for modeling the uptake and food chain transport of radionuclides in fish have usually been conservative; that is, at the high end of reported values. This practice ensures that the dose to the consumer of contaminated fish will not be underestimated. In many models, however, conservative values have been used for all variables that have any uncertainty associated with them. As a result the dose to the consumer is overestimated. Realistic CR values need to be developed to establish model parameters that will accurately reflect tissue burdens in fish and resulting dose rates to consumers. This report reviews and summarizes published literature on the uptake and distribution of stable and radioactive isotopes of 26 elements. Based on this review, we have made recommendations on CR values to be used for modeling the accumulation of radionuclides in fish. Our recommendations are compared with CR values reported in other publications. A generic discussion of abiotic and biotic factors that influence CR values is provided so that CR values may be adjusted based on site-specific characteristics of the fishes habitat. Recommended CR values for freshwater fish and for marine fish are listed. Although this report emphasizes radionuclides, it is applicable to stable elements as well

  1. Concentrations of radionuclides and selected stable elements in fruits and vegetables

    International Nuclear Information System (INIS)

    Oakes, T.W.; Shank, K.E.

    1977-01-01

    Twenty-two types of fruits and vegetables collected from two commercial supermarkets have been analyzed for their radionuclidic and stable-element composition. A specific gamma-emitting isotope analysis was performed on each sample for 40 K, 60 Co, 95 Zr-Nb, 106 Ru, 137 Cs, 226 Ra, and 232 Th. The concentration of the stable elements in each sample were determined using multi-element neutron-activation analysis (Al, Ag, Au, As, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Cu, Eu, Fe, Hf, I, K, La, Mn, Mo, Mg, Na, Rb, Sb, Sc, Se, Sr, Ta, Te, Th, Ti, Zn, Zr) and atomic absorption (Cd, Ni, Pb). Information on the composition of a typical diet is used to estimate the radiological dose to man subsequent to ingestion of these fruits and vegetables. The stable-elemental compositions of the foodstuffs analyzed were compared with estimated values assuming foliar deposition and long-term buildup of effluents from a large modern coal-fired steam plant. It is tentatively concluded that for the general case of a precipitator-equipped, coal-fired steam plant, no toxic levels of trace elements in foodstuffs are expected as a result of the plant operation

  2. Modelling Distribution Function of Surface Ozone Concentration for Selected Suburban Areas in Malaysia

    International Nuclear Information System (INIS)

    Muhammad Izwan Zariq Mokhtar; Nurul Adyani Ghazali; Muhammad Yazid Nasir; Norhazlina Suhaimi

    2016-01-01

    Ozone is known as an important secondary pollutant in the atmosphere. The aim of this study is to find the best fit distribution for calculating exceedance and return period of ozone based on suburban areas; Perak (AMS1) and Pulau Pinang (AMS2). Three distributions namely Gamma, Rayleigh and Laplace were used to fit 2 years ozone data (2010 and 2011). The parameters were estimated by using Maximum Likelihood Estimation (MLE) in order to plot probability distribution function (PDF) and cumulative distribution function (CDF). Four performance indicators were used to find the best distribution namely, normalized absolute error (NAE), prediction accuracy (PA), coefficient of determination (R 2 ) and root mean square error (RMSE). The best distribution to represent ozone concentration at both sites in 2010 and 2011 is Gamma distribution with the smallest error measure (NAE and RMSE) and the highest adequacy measure (PA and R 2 ). For the 2010 data, AMS1 was predicted to exceed 0.1 ppm for 2 days in 2011 with a return period of one occurrence. (author)

  3. Selection of propolis Tetragonula sp. extract solvent with flavonoids and polyphenols concentration and antioxidant activity parameters

    Science.gov (United States)

    Christina, Daisy; Hermansyah, Heri; Wijanarko, Anondho; Rohmatin, Etin; Sahlan, Muhamad; Pratami, Diah Kartika; Mun'im, Abdul

    2018-02-01

    Antioxidants are inhibitory compounds that can inhibit auto oxidation reaction by binding to free radicals and highly reactive molecules. The human body needs antioxidant. Antioxidants can be obtained from a variety of natural ingredients, including propolis. Propolis is the natural sap of the bees, obtained from the herbs around the honeycomb. Ethanol is the solvent that often used to extract propolis. Although it has many advantages, ethanol also has weaknesses such as intolerance to alcohol by some people. Therefore, this research was to extract propolis Tetragonula sp. coarse (C) and soft (S) using four varieties of organic solvent, i.e. olive oil (OO), virgin coconut oil (VCO), propylene glycol (PG), and lecithin (L). It was expected to get the best solvent in extracting propolis. The selection of the best solvent was determined by total flavonoids and polyphenols content assay and antioxidant activity. At each test, the absorbance value read by a microplate reader. Flavonoids content assay is using AlCl3 method with best result on rough-VCO propolis extract of 2509,767 ± 615,02 µg/mL. Polyphenols content assay was using Folin Ciocalteu method with the best results on soft-VCO propolis extract of 1391 ± 171.47 µg/mL. Antioxidant activity assay is using DPPH method with best result on soft-VCO propolis extract with IC50 value of 1,559 ± 0,222 µg/mL.

  4. Concentrations, Deposition, and Effects of Nitrogenous Pollutants in Selected California Ecosystems

    Directory of Open Access Journals (Sweden)

    Andrzej Bytnerowicz

    2001-01-01

    Full Text Available Atmospheric deposition of nitrogen (N in California ecosystems is ecologically significant and highly variable, ranging from about 1 to 45 kg/ha/year. The lowest ambient concentrations and deposition values are found in the eastern and northern parts of the Sierra Nevada Mountains and the highest in parts of the San Bernardino and San Gabriel Mountains that are most exposed to the Los Angeles air pollution plume. In the Sierra Nevada Mountains, N is deposited mostly in precipitation, although dry deposition may also provide substantial amounts of N. On the western slopes of the Sierra Nevada, the majority of airborne N is in reduced forms as ammonia (NH3 and particulate ammonium (NH4+ from agricultural activities in the California Central Valley. In southern California, most of the N air pollution is in oxidized forms as nitrogen oxides (NOx, nitric acid (HNO3, and particulate nitrate (NO3– resulting from fossil fuel combustion and subsequent complex photochemical reactions. In southern California, dry deposition of gases and particles provides most (up to 95% of the atmospheric N to forests and other ecosystems. In the mixed-conifer forest zone, elevated deposition of N may initially benefit growth of vegetation, but chronic effects may be expressed as deterioration of forest health and sustainability. HNO3 vapor alone has a potential for toxic effects causing damage of foliar surfaces of pines and oaks. In addition, dry deposition of predominantly HNO3 has lead to changes in vegetation composition and contamination of ground- and stream water where terrestrial N loading is high. Long-term, complex interactions between N deposition and other environmental stresses such as elevated ozone (O3, drought, insect infestations, fire suppression, or intensive land management practices may affect water quality and sustainability of California forests and other ecosystems.

  5. Marrubium vulgare L.: A review on phytochemical and pharmacological aspects

    Directory of Open Access Journals (Sweden)

    Santram Lodhi

    2017-12-01

    Full Text Available Marrubium vulgare L. (family: Lamiaceae, also known as white horehound, is widely used as herbal remedy for chronic coughs and colds. It is used in various disorders related to skin, liver, gastric, heart and immune system. This review abridges phytochemical, pharmacological studies and medicinal uses of M. vulgare and provides scientific proof for various ethnobotanical claims in order to identify gaps, which will give impulsion for novel research on M. vulgare based herbal medicines. This review summarizes selected scientific evidence on phytochemistry and pharmacological properties of M. vulgare over the past 48 years (1968 to 2016. The work reported on M. vulgare was reviewed from various sources like books, internet source i.e. google search engine, pubmed, sciencedirect and chemical abstract. The exhaustive literature was studied and critical analysis was done according to their phytochemical and pharmacological properties. Phytochemical investigations on different parts of M. vulgare have been reported the presence of flavonoids, steroids, terpenoids, tannins, saponins and volatile oils (0.05%. The aerial parts contain marrubiin, together with ursolic acid and choline. Pharmacological activities like, anti-nociceptive, anti-spasmodic, anti-hypertensive, anti-diabetic, gastroprotective, anti-inflammatory, anti-microbial, anti-cancer, antioxidant, and anti-hepatotoxic activity have been reported. M. vulgare has therapeutic potential in the treatment of inflammatory conditions, liver disorders, pain, cardiovascular, gastric and diabetic conditions. Aerial parts of M. vulgare is a good source of labdane type diterpene especially marrubiin which is present in high concentrations. However, further scientific studies are needed to explore clinical efficacy, toxicity and to explore the therapeutic effect of major secondary metabolites like diterpenes, phenylpropanoid and phenylethanoid glycosides of M. vulgare. [J Complement Med Res 2017; 6

  6. CLINICAL PHARMACOLOGY OF DIURETICS

    Directory of Open Access Journals (Sweden)

    I. V. Soldatenko

    2014-06-01

    Full Text Available Clinical pharmacology of diuretics in the international system of ATC (anatomic-therapeutic-chemical is presented. Classification of this group by the action mechanism and caused effects is provided. Pharmacokinetics and pharmacodynamics features, indications and principles of diuretics usage in clinics are considered. Contraindications, side effects and interaction with other drugs of this group are discussed in detail.

  7. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  8. Particulate matter and polycyclic aromatic hydrocarbons in a selected athletic hall: ambient concentrations, origin and effects on human health

    Science.gov (United States)

    Kuskowska, Karolina; Rogula-Kozłowska, Wioletta; Rogula-Kopiec, Patrycja

    2018-01-01

    The paper presents the results of research on the concentration of 16 polycyclic aromatic hydrocarbons (PAHs) associated with total suspended particles (TSP) and their respirable fraction (PM4) in one of the Warsaw sports halls. Samples of dust were collected for 15 days simultaneously inside and outside (atmospheric air) of the sports hall. The obtained data allowed calculating diagnostic ratios indicating the origin of the PAHs and selected indicators of cumulative exposure to the PAH mixture. Both PM and PAH in the surveyed area were derived from the combustion of solid fuels; this involved pollution both in the atmospheric air and in the air inside the sports hall. It has been shown that the exposure of sports hall users to PAHs is significantly higher than the exposure resulting from concentrations recorded in the atmospheric air.

  9. Particulate matter and polycyclic aromatic hydrocarbons in a selected athletic hall: ambient concentrations, origin and effects on human health

    Directory of Open Access Journals (Sweden)

    Kuskowska Karolina

    2018-01-01

    Full Text Available The paper presents the results of research on the concentration of 16 polycyclic aromatic hydrocarbons (PAHs associated with total suspended particles (TSP and their respirable fraction (PM4 in one of the Warsaw sports halls. Samples of dust were collected for 15 days simultaneously inside and outside (atmospheric air of the sports hall. The obtained data allowed calculating diagnostic ratios indicating the origin of the PAHs and selected indicators of cumulative exposure to the PAH mixture. Both PM and PAH in the surveyed area were derived from the combustion of solid fuels; this involved pollution both in the atmospheric air and in the air inside the sports hall. It has been shown that the exposure of sports hall users to PAHs is significantly higher than the exposure resulting from concentrations recorded in the atmospheric air.

  10. Oesophageal cancer in the Transkei. Determination of trace element concentrations in selected plant material by instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Renan, M.J.; Drennan, B.D.; Keddy, R.J.; Sellschop, J.P.F.

    1979-01-01

    The results of the analysis by instrumental neutron activation for the concentration of trace elements in plant materials from certain areas in the Transkei region of southern Africa are presented. These areas are selected for their characteristic high or low incidence of carcinoma of the oesophagus. To broaden the suite of elements for which analysed and to overcome some of the limitations of neutron activation analysis, certain other nuclear analyses and methods are suggested which, if utilized, would increase the number of elements determined, and so improve the information available. (author)

  11. Sex differences in the pharmacological treatment of hypertension : a review of population-based studies

    NARCIS (Netherlands)

    Klungel, O.H.; de Boer, A; Paes, A.H.P.; Seidell, J C; Bakker, A

    OBJECTIVE: To summarize all available literature on sex differences in the pharmacological treatment of hypertension with respect to the percentage of hypertensive patients treated pharmacologically and the selection of antihypertensive drugs. The influences of the calendar period, age, definition

  12. Low concentrations of Rhodamine-6G selectively destroy tumor cells and improve survival of melanoma transplanted mice.

    Science.gov (United States)

    Kutushov, M; Gorelik, O

    2013-01-01

    Rhodamine-6G is a fluorescent dye binding to mitochondria, thus reducing the intact mitochondria number and inhibiting mitochondrial metabolic activity. Resultantly, the respiratory chain functioning becomes blocked, the cell "suffocated" and eventually destroyed. Unlike normal cells, malignant cells demonstrate a priori reduced mitochondrial numbers and aberrant metabolism. Therefore, a turning point might exist, when Rhodamine-induced loss of active mitochondria would selectively destroy malignant, but spare normal cells. Various malignant vs. non-malignant cell lines were cultured with Rhodamine-6G at different concentrations. In addition, C57Bl mice were implanted with B16-F10 melanoma and treated with Rhodamine-6G at different dosage/time regimens. Viability and proliferation of cultured tumor cells were time and dose-dependently inhibited, up to 90%, by Rhodamine-6G, with profound histological signs of cell death. By contrast, inhibition of normal control cell proliferation hardly exceeded 15-17%. Melanoma-transplanted mice receiving Rhodamine-6G demonstrated prolonged survival, improved clinical parameters, inhibited tumor growth and metastases count, compared to their untreated counterparts. Twice-a-week 10-6M Rhodamine-6G regimen yielded the most prominent results. We conclude that malignant, but not normal, cells are selectively destroyed by low doses of Rhodamine-6G. In vivo, such treatment selectively suppresses tumor progression and dissemination, thus improving prognosis. We suggest that selective anti-tumor properties of Rhodamine-6G are based on unique physiologic differences in energy metabolism between malignant and normal cells. If found clinically relevant, low concentrations of Rhodamine-6G might be useful for replacing, or backing up, more aggressive nonselective chemotherapeutic compounds.

  13. Assessment of Heavy Metals Concentration in Soils at Selected Points on Roads and Sites Around Nairobi Using EDXRF Spectrometer

    International Nuclear Information System (INIS)

    Wanjala, O. F.; Rathore, I.V.S.; Murungi, J.

    2016-01-01

    Increased exhaust emissions (gaseous and particulate), fuel leakage, damping and wear and tear of vehicle parts have resulted in environmental pollution by heavy metals especially along major roads with high traffic. This calls for constant monitoring to make sure that the levels of heavy metals do not go above the threshold limits recommended due to their adverse health effects on human beings, plants and animals. This research project focused on determining the present concentrations of heavy metals (Pb, Zn, Cu, and Ni) in soils at selected points on roads around Nairobi and some selected sites with respect to distance off-road and depth. The soil samples collected were ground into fine particles of size less than 100m and prepared into pellet form for analysis using Energy Dispersive X-ray fluorescence spectrometry. This analytic technique is fast, non-destructive and enables simultaneous determination of the concentrations of many elements in a sample with high sensitivity. It consists of a Si(Li) detector with energy resolution between 170eV to 190eV at 5.9KeV, MnKα-lines and a radioisotope source 109Cd (T1/2 =461.4 days) for sample excitation leading to emission of characteristic X-rays. Quantitative analysis was done using a software program called Quantitative X-ray Analysis System with a sub-routine program called Quantitative Analysis of Environmental Samples to finally obtain the concentrations of the different elements in the samples. The levels of the heavy metals obtained from the selected sampling sites C.Gar, K. Gar, K.R, G.B.P and Nai were 82.2±7.6, g/g to 236.1±9.2, g/g Pb, 273±9.2, g/g to 794±26, g/gZn, 32.4±4.8, g/g to 221.8±6.8, g/g Cu, and 10.72.7, g/g to 33±4.8, g/g Ni. From the results, it was found that the concentrations of Pb, Zn, Cu, and Ni were very high at the garages followed by parking places for buses and heavy commercial vehicles and lastly at roundabouts. The concentrations of heavy metals on the selected roads at Roy, Cab

  14. Mechanisms responsible for imipenem resistance among Pseudomonas aeruginosa clinical isolates exposed to imipenem concentrations within the mutant selection window.

    Science.gov (United States)

    Vassilara, Foula; Galani, Irene; Souli, Maria; Papanikolaou, Konstantinos; Giamarellou, Helen; Papadopoulos, Antonios

    2017-07-01

    The aim of this study was to determine the propensities of imipenem to select for resistant Pseudomonas aeruginosa mutants by determining the mutant prevention concentrations (MPCs) for 9 unrelated clinical isolates and the accession of any relationship with mechanisms of resistance development. The MPC/MIC ratios ranged from 4 to 16. Detection of resistance mechanisms in the mutant derivatives of the nine isolates mainly revealed inactivating mutations in the gene coding for outer membrane protein OprD. Point mutations leading to premature stop codons or amino acid substitution S278P, ≥1bp deletion leading to frameshift mutations and interruption of the oprD by an insertion sequence, were observed. MPC and mutant selection window (MSW) are unique parameters that may guide the implementation of antimicrobial treatment, providing useful information about the necessary imipenem concentration needed in the infection area, in order to avoid the emergence of resistance, especially in clinical situations with high bacterial load. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. International Union of Basic and Clinical Pharmacology Review: WNT/Frizzled signalling: receptor–ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3

    Science.gov (United States)

    Dijksterhuis, J P; Petersen, J; Schulte, G

    2014-01-01

    The wingless/int1 (WNT)/Frizzled (FZD) signalling pathway controls numerous cellular processes such as proliferation, differentiation, cell-fate decisions, migration and plays a crucial role during embryonic development. Nineteen mammalian WNTs can bind to 10 FZDs thereby activating different downstream pathways such as WNT/β-catenin, WNT/planar cell polarity and WNT/Ca2+. However, the mechanisms of signalling specification and the involvement of heterotrimeric G proteins are still unclear. Disturbances in the pathways can lead to various diseases ranging from cancer, inflammatory diseases to metabolic and neurological disorders. Due to the presence of seven-transmembrane segments, evidence for coupling between FZDs and G proteins and substantial structural differences in class A, B or C GPCRs, FZDs were grouped separately in the IUPHAR GPCR database as the class FZD within the superfamily of GPCRs. Recently, important progress has been made pointing to a direct activation of G proteins after WNT stimulation. WNT/FZD and G protein coupling remain to be fully explored, although the basic observation supporting the nature of FZDs as GPCRs is compelling. Because the involvement of different (i) WNTs; (ii) FZDs; and (iii) intracellular binding partners could selectively affect signalling specification, in this review we present the current understanding of receptor/ligand selectivity of FZDs and WNTs. We pinpoint what is known about signalling specification and the physiological relevance of these interactions with special emphasis on FZD–G protein interactions. LINKED ARTICLESThis article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-5 PMID:24032637

  16. Delirium in the elderly: A systematic review of pharmacological and non-pharmacological treatments

    Directory of Open Access Journals (Sweden)

    Cecília Carboni Tardelli Cerveira

    Full Text Available ABSTRACT Delirium is a common disorder associated with poor prognosis, especially in the elderly. The impact of different treatment approaches for delirium on morbimortality and long-term welfare is not completely understood. OBJECTIVE: To determine the efficacy of pharmacological and non-pharmacological treatments in elderly patients with delirium. METHODS: This systematic review compared pharmacological and non-pharmacological treatments in patients over 60 years old with delirium. Databases used were: MEDLINE (PubMed, EMBASE, Cochrane CENTRAL and LILACS from inception to January 6th, 2016. RESULTS: A total of ten articles were selected. The six non-pharmacological intervention studies showed no impact on duration of delirium, mortality or institutionalization, but a decrease in severity of delirium and improvement in medium-term cognitive function were observed. The most commonly used interventions were temporal-spatial orientation, orientation to self and others, early mobilization and sleep hygiene. The four studies with pharmacological interventions found that rivastigmine reduced the duration of delirium, improved cognitive function and reduced caregiver burden; olanzapine and haloperidol decreased the severity of delirium; droperidol reduced length of hospitalization and improved delirium remission rate. CONCLUSION: Although the pharmacological approach has been used in the treatment of delirium among elderly, there have been few studies assessing its efficacy, involving a small number of patients. However, the improvements in delirium duration and severity suggest these drugs are effective in treating the condition. Once delirium has developed, non-pharmacological treatment seems less effective in controlling symptoms, and there is a lack of studies describing different non-pharmacological interventions.

  17. Pharmacological Investigation of Selected Medicinal Plants of ...

    African Journals Online (AJOL)

    noticeable decrease of exploratory behavior in the test animals from its initial value at 0 to 120 min (Table 2). The results were dose-dependent and significant at p < 0.05 level, At 30 min,. VNME (500 mg/ kg) and VNPE (250 mg/ kg) are significant compared to standard. At 60 min, all test samples are significant compared to.

  18. [Pharmacological therapy of obesity].

    Science.gov (United States)

    Pagotto, Uberto; Vanuzzo, Diego; Vicennati, Valentina; Pasquali, Renato

    2008-04-01

    Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and

  19. Pharmacological and non- pharmacological treatment of hypertension: A review article

    Directory of Open Access Journals (Sweden)

    Marjan Seyedmazhari

    2013-01-01

    Full Text Available BACKGROUND: Hypertension is a worldwide epidemic disease. It is more common and more severe in elderly persons. Various studies however have estimated 41.9 million men and 27.8 million women to have prehypertension. Diagnosis and early treatment of prehypertension are of utmost importance. Although hypertension is usually divided into 2 general categories of essential (primary and secondary hypertension, the initial treatment for hypertension often depends on its stage which is determined by systolic and diastolic blood pressure. Lifestyle modification is the first step in treating stage one hypertension. Pharmaceutical treatments including diuretics, angiotensin converting enzyme (ACE inhibitors, calcium blockers, beta blockers, and angiotensin receptor blockers will be recommended if lifestyle modification fails to control blood pressure.    METHODS: The PubMed database was searched by a number of keywords including hypertension, pharmaceutical treatment, and non-pharmaceutical treatment. The results were limited by determining a date range of 2008-11.    RESULTS: High blood pressure causes major health problems for many people around the world. It should be controlled because of its high mortality and morbidity. However, in order to select an appropriate treatment modality, it is initially important to diagnose the kinds and stages of hypertension. Pharmaceutical or non-pharmaceutical treatments can then be employed to control this serious disease.    CONCLUSION: Treating hypertension depends on the kinds and stages of this disease. Several tips should be considered when selecting a method of treatment.       Keywords: Hypertension, Pharmacological treatment, Non-pharmacological treatment

  20. Pharmacological screening technologies for venom peptide discovery.

    Science.gov (United States)

    Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina

    2017-12-01

    Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Pharmacological interactions of vasoconstrictors.

    Science.gov (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-01-01

    This article is the first of a series on pharmacological interactions involving medicaments commonly prescribed and/or used in odontology: vasoconstrictors in local anaesthetics and anti-inflammatory and anti-microbial analgesics. The necessity for the odontologist to be aware of adverse reactions as a result of the pharmacological interactions is due to the increase in medicament consumption by the general population. There is a demographic change with greater life expectancy and patients have increased chronic health problems and therefore have increased medicament intake. The presence of adrenaline (epinephrine) and other vasoconstrictors in local odontological anaesthetics is beneficial in relation to the duration and depth of anaesthesia and reduces bleeding and systemic toxicity of the local anaesthetic. However, it might produce pharmacological interactions between the injected vasoconstrictors and the local anaesthetic and adrenergic medicament administered exogenically which the odontologist should be aware of, especially because of the risk of consequent adverse reactions. Therefore the importance of conducting a detailed clinical history of the general state of health and include all medicaments, legal as well as illegal, taken by the patient.

  2. Dredging effects on selected nutrient concentrations and ecoenzymatic activity in two drainage ditch sediments in the lower Mississippi River Valley

    Directory of Open Access Journals (Sweden)

    Matt Moore

    2017-09-01

    Full Text Available Agricultural drainage ditches are conduits between production acreage and receiving aquatic systems. Often overlooked for their mitigation capabilities, agricultural drainage ditches provide an important role for nutrient transformation via microbial metabolism. Variations in ecoenzyme activities have been used to elucidate microbial metabolism and resource demand of microbial communities to better understand the relationship between altered nutrient ratios and microbial activity in aquatic ecosystems. Two agricultural drainage ditches, one in the northeast portion of the Arkansas Delta and the other in the lower Mississippi Delta, were monitored for a year. Sediment samples were collected prior to each ditch being dredged (cleaned, and subsequent post-dredging samples occurred as soon as access was available. Seasonal samples were then collected throughout a year to examine effects of dredging on selected nutrient concentrations and ecoenzymatic activity recovery in drainage ditch sediments. Phosphorus concentrations in sediments after dredging decreased 33–66%, depending on ditch and phosphorus extraction methodology. Additionally, ecoenzymatic activity was significantly decreased in most sediment samples after dredging. Fluorescein diacetate hydrolysis activity, an estimate of total microbial activity, decreased 56–67% after dredging in one of the two ditches. Many sample sites also had significant phosphorus and ecoenzymatic activity differences between the post-dredge samples and the year-long follow-up samples. Results indicate microbial metabolism in dredged drainage ditches may take up to a year or more to recover to pre-dredged levels. Likewise, while sediment nutrient concentrations may be decreased through dredging and removal, runoff and erosion events over time tend to quickly replenish nutrient concentrations in replaced sediments. Understanding nutrient dynamics and microbial metabolism within agricultural drainage ditches is

  3. Rich: Region-based Intelligent Cluster-Head Selection and Node Deployment Strategy in Concentric-based WSNs

    Directory of Open Access Journals (Sweden)

    FAN, C.-S.

    2013-11-01

    Full Text Available In a random deployment, sensor nodes are scattered randomly in the sensing field. Hence, the coverage can not be guaranteed. In contrast, the coverage of uniformly deployment is in general larger than the random deployment. However, uniformly deployment strategy may cause unbalanced traffic pattern in wireless sensor networks (WSNs. In this situation, larger load may be imposed to CHs (cluster heads around the sink. Therefore, CHs close to the sink use up their energy earlier than those farther away from the sink. To overcome this problem, we propose a novel node deployment strategy in the concentric model, namely, Region-based Intelligent Cluster-Head selection and node deployment strategy (called Rich. The coverage, energy consumption and data routing issues are well investigated and taken into consideration in the proposed Rich scheme. The simulation results show that the proposed Rich alleviates the unbalanced traffic pattern significantly, prolongs network lifetime and achieves satisfactory coverage ratio.

  4. Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

    Science.gov (United States)

    Song, Yong-Ak; Melik, Rohat; Rabie, Amr N.; Ibrahim, Ahmed M. S.; Moses, David; Tan, Ara; Han, Jongyoon; Lin, Samuel J.

    2011-12-01

    Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.

  5. Assessment of fetal activity concentration and fetal dose for selected radionuclides based on animal and human data

    International Nuclear Information System (INIS)

    Roedler, H.D.

    1987-01-01

    Biokinetic data of selected radionuclide compounds from investigations in man and animal were taken from literature references with the purpose to provide a basis for a comparative assessment of fetal and adult radiation doses after intake or administration of radionuclides. The following ratios of fetal to adult doses were derived from human data: 0.5 for caesium 137 and total body, 2.3 for iron 59 and liver, 0.06 - 0.3 - 1.1 for iodine 131 and thyroid, and 0.1 - 0.3 for strontium 90 and bone. The ratios of activity concentrations in fetal and adult tissues are of considerable variability - up to three orders of magnitude. Further studies on fetal and adult biokinetics specifically designed for comparative dose assessment are indispensable. 106 refs.; 6 tabs

  6. Evaluation of synthetic water-soluble metal-binding polymers with ultrafiltration for selective concentration of americium and plutonium

    International Nuclear Information System (INIS)

    Smith, B.F.; Gibson, R.R.; Jarvinen, G.D.; Jones, M.M.; Lu, M.T.; Robison, T.W.; Schroeder, N.C.; Stalnaker, N.

    1997-01-01

    Routine counting methods and ICP-MS are unable to directly measure the new US Department of Energy (DOE) regulatory level for discharge waters containing alpha-emitting radionuclides of 30 pCi/L total alpha or the 0.05 pCi/L regulatory level for Pu or Am activity required for surface waters at the Rocky Flats site by the State of Colorado. This inability indicates the need to develop rapid, reliable, and robust analytical techniques for measuring actinide metal ions, particularly americium and plutonium. Selective separation or preconcentration techniques would aid in this effort. Water-soluble metal-binding polymers in combination with ultrafiltration are shown to be an effective method for selectively removing dilute actinide ions from acidic solutions of high ionic strength. The actinide-binding properties of commercially available water-soluble polymers and several polymers which have been reported in the literature were evaluated. The functional groups incorporated in the polymers were pyrrolidone, amine, oxime, and carboxylic, phosphonic, or sulfonic acid. The polymer containing phosphonic acid groups gave the best results with high distribution coefficients and concentration factors for 241 Am(III) and 238 Pu(III)/(IV) at pH 4 to 6 and ionic strengths of 0.1 to 4

  7. Prediction of suspended-sediment concentrations at selected sites in the Fountain Creek watershed, Colorado, 2008-09

    Science.gov (United States)

    Stogner, Sr., Robert W.; Nelson, Jonathan M.; McDonald, Richard R.; Kinzel, Paul J.; Mau, David P.

    2013-01-01

    In 2008, the U.S. Geological Survey (USGS), in cooperation with Pikes Peak Area Council of Governments, Colorado Water Conservation Board, Colorado Springs City Engineering, and the Lower Arkansas Valley Water Conservancy District, began a small-scale pilot study to evaluate the effectiveness of the use of a computational model of streamflow and suspended-sediment transport for predicting suspended-sediment concentrations and loads in the Fountain Creek watershed in Colorado. Increased erosion and sedimentation damage have been identified by the Fountain Creek Watershed Plan as key problems within the watershed. A recommendation in the Fountain Creek Watershed plan for management of the basin is to establish measurable criteria to determine if progress in reducing erosion and sedimentation damage is being made. The major objective of this study was to test a computational method to predict local suspended-sediment loads at two sites with different geomorphic characteristics in order to evaluate the feasibility of using such an approach to predict local suspended-sediment loads throughout the entire watershed. Detailed topographic surveys, particle-size data, and suspended-sediment samples were collected at two gaged sites: Monument Creek above Woodmen Road at Colorado Springs, Colorado (USGS gage 07103970), and Sand Creek above mouth at Colorado Springs, Colorado (USGS gage 07105600). These data were used to construct three-dimensional computational models of relatively short channel reaches at each site. The streamflow component of these models predicted a spatially distributed field of water-surface elevation, water velocity, and bed shear stress for a range of stream discharges. Using the model predictions, along with measured particle sizes, the sediment-transport component of the model predicted the suspended-sediment concentration throughout the reach of interest. These computed concentrations were used with predicted flow patterns and channel morphology to

  8. Pharmacological Profile of Quinoxalinone

    Directory of Open Access Journals (Sweden)

    Youssef Ramli

    2014-01-01

    Full Text Available Quinoxalinone and its derivatives are used in organic synthesis for building natural and designed synthetic compounds and they have been frequently utilized as suitable skeletons for the design of biologically active compound. This review covers updated information on the most active quinoxalinone derivatives that have been reported to show considerable pharmacological actions such as antimicrobial, anti-inflammatory, antidiabetic, antiviral, antitumor, and antitubercular activity. It can act as an important tool for chemists to develop newer quinoxalinone derivatives that may prove to be better agents in terms of efficacy and safety.

  9. Well-constructed cellulose acetate membranes for forward osmosis: Minimized internal concentration polarization with an ultra-thin selective layer

    KAUST Repository

    Zhang, Sui

    2010-09-01

    The design and engineering of membrane structure that produces low salt leakage and minimized internal concentration polarization (ICP) in forward osmosis (FO) processes have been explored in this work. The fundamentals of phase inversion of cellulose acetate (CA) regarding the formation of an ultra-thin selective layer at the bottom interface of polymer and casting substrate were investigated by using substrates with different hydrophilicity. An in-depth understanding of membrane structure and pore size distribution has been elucidated with field emission scanning electronic microscopy (FESEM) and positron annihilation spectroscopy (PAS). A double dense-layer structure is formed when glass plate is used as the casting substrate and water as the coagulant. The thickness of the ultra-thin bottom layer resulted from hydrophilic-hydrophilic interaction is identified to be around 95nm, while a fully porous, open-cell structure is formed in the middle support layer due to spinodal decomposition. Consequently, the membrane shows low salt leakage with mitigated ICP in the FO process for seawater desalination. The structural parameter (St) of the membrane is analyzed by modeling water flux using the theory that considers both external concentration polarization (ECP) and ICP, and the St value of the double dense-layer membrane is much smaller than those reported in literatures. Furthermore, the effects of an intermediate immersion into a solvent/water mixed bath prior to complete immersion in water on membrane formation have been studied. The resultant membranes may have a single dense layer with an even lower St value. A comparison of fouling behavior in a simple FO-membrane bioreactor (MBR) system is evaluated for these two types of membranes. The double dense-layer membrane shows a less fouling propensity. This study may help pave the way to improve the membrane design for new-generation FO membranes. © 2010 Elsevier B.V.

  10. Subminimal Inhibitory Concentrations of the Disinfectant Benzalkonium Chloride Select for a Tolerant Subpopulation of Escherichia coli with Inheritable Characteristics

    Directory of Open Access Journals (Sweden)

    Solveig Langsrud

    2012-03-01

    Full Text Available Exposure of Escherichia coli to a subminimal inhibitory concentration (25% below MIC of benzalkonium chloride (BC, an antimicrobial membrane-active agent commonly used in medical and food-processing environments, resulted in cell death and changes in cell morphology (filamentation. A small subpopulation (1–5% of the initial population survived and regained similar morphology and growth rate as non-exposed cells. This subpopulation maintained tolerance to BC after serial transfers in medium without BC. To withstand BC during regrowth the cells up regulated a drug efflux associated gene (the acrB gene, member of the AcrAB-TolC efflux system and changed expression of outer membrane porin genes (ompFW and several genes involved in protecting the cell from the osmotic- and oxidative stress. Cells pre-exposed to osmotic- and oxidative stress (sodium chloride, salicylic acid and methyl viologen showed higher tolerance to BC. A control and two selected isolates showing increased BC-tolerance after regrowth in BC was genome sequenced. No common point mutations were found in the BC- isolates but one point mutation in gene rpsA (Ribosomal protein S1 was observed in one of the isolates. The observed tolerance can therefore not solely be explained by the observed point mutation. The results indicate that there are several different mechanisms responsible for the regrowth of a tolerant subpopulation in BC, both BC-specific and general stress responses, and that sub-MIC of BC may select for phenotypic variants in a sensitive E. coli culture.

  11. Mercury concentrations in water, and mercury and selenium concentrations in fish from Brownlee Reservoir and selected sites in Boise and Snake Rivers, Idaho and Oregon, 2013

    Science.gov (United States)

    MacCoy, Dorene E.

    2014-01-01

    Mercury (Hg) analyses were conducted on samples of sport fish and water collected from six sampling sites in the Boise and Snake Rivers, and Brownlee Reservoir to meet National Pollution Discharge and Elimination System (NPDES) permit requirements for the City of Boise, Idaho. A water sample was collected from each site during October and November 2013 by the City of Boise personnel and was analyzed by the Boise City Public Works Water Quality Laboratory. Total Hg concentrations in unfiltered water samples ranged from 0.73 to 1.21 nanograms per liter (ng/L) at five river sites; total Hg concentration was highest (8.78 ng/L) in a water sample from Brownlee Reservoir. All Hg concentrations in water samples were less than the EPA Hg chronic aquatic life criterion in Idaho (12 ng/L). The EPA recommended a water-quality criterion of 0.30 milligrams per kilogram (mg/kg) methylmercury (MeHg) expressed as a fish-tissue residue value (wet-weight MeHg in fish tissue). MeHg residue in fish tissue is considered to be equivalent to total Hg in fish muscle tissue and is referred to as Hg in this report. The Idaho Department of Environmental Quality adopted the EPA’s fish-tissue criterion and a reasonable potential to exceed (RPTE) threshold 20 percent lower than the criterion or greater than 0.24 mg/kg based on an average concentration of 10 fish from a receiving waterbody. NPDES permitted discharge to waters with fish having Hg concentrations exceeding 0.24 mg/kg are said to have a reasonable potential to exceed the water-quality criterion and thus are subject to additional permit obligations, such as requirements for increased monitoring and the development of a Hg minimization plan. The Idaho Fish Consumption Advisory Program (IFCAP) issues fish advisories to protect general and sensitive populations of fish consumers and has developed an action level of 0.22 mg/kg wet weight Hg in fish tissue. Fish consumption advisories are water body- and species-specific and are used to

  12. ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.

    Science.gov (United States)

    Langlois, Daniel K; Fritz, Michele C; Schall, William D; Bari Olivier, N; Smedley, Rebecca C; Pearson, Paul G; Bailie, Marc B; Hunt, Stephen W

    2018-05-02

    Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of

  13. Pharmacological therapy for amblyopia

    Directory of Open Access Journals (Sweden)

    Anupam Singh

    2017-01-01

    Full Text Available Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time, penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents.

  14. Pharmacological therapy for amblyopia

    Science.gov (United States)

    Singh, Anupam; Nagpal, Ritu; Mittal, Sanjeev Kumar; Bahuguna, Chirag; Kumar, Prashant

    2017-01-01

    Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents. PMID:29018759

  15. Methods for estimating concentrations and loads of selected constituents in tributaries to Lake Houston near Houston, Texas

    Science.gov (United States)

    Lee, Michael T.

    2012-01-01

    Since December 2005, the U.S. Geological Survey, in cooperation with the City of Houston, Texas, has been assessing the quality of the water flowing into Lake Houston. Continuous in-stream water-quality monitors measured streamflow and other physical water quality properties at stations in Spring Creek near Spring, Tex., and East Fork San Jacinto River near New Caney, Tex. Additionally, discrete water-quality samples were periodically collected on these tributaries and analyzed for selected constituents of concern. Data from the discrete water-quality samples collected during 2005-9, in conjunction with the real-time streamflow data and data from the continuous in-stream water-quality monitors, provided the basis for developing regression equations for the estimation of concentrations of water-quality constituents of these source watersheds to Lake Houston. The output of the regression equations are available through the interactive National Real-Time Water Quality Web site (http://nrtwq.usgs.gov).

  16. Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

    Science.gov (United States)

    Lötsch, Jörn; Ultsch, Alfred

    2016-04-01

    A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  17. Pharmacology and function of melatonin receptors

    International Nuclear Information System (INIS)

    Dubocovich, M.L.

    1988-01-01

    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-[125I]iodomelatonin are identical. It is proposed that 2-[125I]iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-[125I]iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references

  18. Pharmacological Effects of Biotin in Animals.

    Science.gov (United States)

    Riveron-Negrete, Leticia; Fernandez-Mejia, Cristina

    2017-01-01

    In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water-soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently-bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Strains of Rodents and the Pharmacology of Learning and Memory

    OpenAIRE

    Ammassari-Teule, Martine; Castellano, Claudio

    2004-01-01

    Mendelian genetic tools have extensively been used to improve the description of the pharmacological mechanisms involved in learning and memory. The first part of this short review describes experiments involving the bidirectional selection of rats or mice for extreme behavioral characteristics or for sensitivity to pharmacological treatments. The second part focuses specifically on inbreeding. In conclusion, the advantages and the limits of a Mendelian pharmacog...

  20. [Pharmacological treatment of obesity].

    Science.gov (United States)

    Gomis Barbará, R

    2004-01-01

    The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.

  1. Pharmacological therapy of spondyloarthritis.

    Science.gov (United States)

    Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

    2015-01-01

    The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

  2. Pharmacology of midazolam.

    Science.gov (United States)

    Pieri, L; Schaffner, R; Scherschlicht, R; Polc, P; Sepinwall, J; Davidson, A; Möhler, H; Cumin, R; Da Prada, M; Burkard, W P; Keller, H H; Müller, R K; Gerold, M; Pieri, M; Cook, L; Haefely, W

    1981-01-01

    8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) is an imidazobenzodiazepine whose salts are soluble and stable in aqueous solution. It has a quick onset and, due to rapid metabolic inactivation, a rather short duration of action in all species studied. Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam. It produces all the characteristic effects of the benzodiazepine class, i.e., anticonvulsant, anxiolytic, sleep-inducing, muscle relaxant, and "sedative" effects. The magnitude of the anticonflict effect of midazolam is smaller than that of diazepam in rats and squirrel monkeys, probably because a more pronounced sedative component interferes with the increase of punished responses. In rodents, surgical anaesthesia is not attained with midazolam alone even in high i.v. doses, whereas this state is obtained in monkeys. The drug potentiates the effect of various central depressant agents. Midazolam is virtually free of effects on the cardiovascular system in conscious animals and produces only slight decreases in cardiac performance in dogs anaesthetized with barbiturates. No direct effects of the drugs on autonomic functions were found, however, stress-induced autonomic disturbances are prevented, probably by an effect on central regulatory systems. All animal data suggest the usefulness of midazolam as a sleep-inducer and i.v. anaesthetic of rapid onset and short duration.

  3. Pharmacology of pediatric resuscitation.

    Science.gov (United States)

    Ushay, H M; Notterman, D A

    1997-02-01

    The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.

  4. Pharmacological Fingerprints of Contextual Uncertainty.

    Directory of Open Access Journals (Sweden)

    Louise Marshall

    2016-11-01

    Full Text Available Successful interaction with the environment requires flexible updating of our beliefs about the world. By estimating the likelihood of future events, it is possible to prepare appropriate actions in advance and execute fast, accurate motor responses. According to theoretical proposals, agents track the variability arising from changing environments by computing various forms of uncertainty. Several neuromodulators have been linked to uncertainty signalling, but comprehensive empirical characterisation of their relative contributions to perceptual belief updating, and to the selection of motor responses, is lacking. Here we assess the roles of noradrenaline, acetylcholine, and dopamine within a single, unified computational framework of uncertainty. Using pharmacological interventions in a sample of 128 healthy human volunteers and a hierarchical Bayesian learning model, we characterise the influences of noradrenergic, cholinergic, and dopaminergic receptor antagonism on individual computations of uncertainty during a probabilistic serial reaction time task. We propose that noradrenaline influences learning of uncertain events arising from unexpected changes in the environment. In contrast, acetylcholine balances attribution of uncertainty to chance fluctuations within an environmental context, defined by a stable set of probabilistic associations, or to gross environmental violations following a contextual switch. Dopamine supports the use of uncertainty representations to engender fast, adaptive responses.

  5. The pharmacology of regenerative medicine.

    Science.gov (United States)

    Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik

    2013-07-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

  6. Tritium concentrations in flow from selected springs that discharge to the Snake River, Twin Falls-Hagerman area, Idaho

    International Nuclear Information System (INIS)

    Mann, L.J.

    1989-01-01

    Concern has been expressed that some of the approximately 30,900 curies of tritium disposed to the Snake River Plain aquifer from 1952 to 1988 at the INEL (idaho National Engineering Laboratory) have migrated to springs discharging to the Snake River in the Twin Falls-Hagerman area. To document tritium concentrations in springflow, 17 springs were sampled in November 1988 and 19 springs were sampled in March 1989. Tritium concentrations were less than the minimum detectable concentration of 0.5 pCi/mL (picocuries/mL) in November 1988 and less than the minimum detectable concentration of 0.2 pCi/mL in March 1989 the minimum detectable concentration was smaller in March 1989. The maximum contaminant level of tritium in drinking water as established by the US Environmental Protection Agency is 20 pCi/mL. US Environmental Protection Agency sample analyses indicate that the tritium concentration has decreased in the Snake River near Buhl since the 1970's. In 1974-79, tritium concentrations were less than 0.3 ± 0.2 pCi/mL in 3 of 20 samples; in 1983-88, 17 of 23 samples contaminated less than 0.3 ± 0.2 pCi/mL of tritium; the minimum detectable concentration is 0.2 pCi/mL. On the basis of decreasing tritium concentrations in the Snake River, their correlation to cessation of atmospheric weapons tests tritium concentrations in springflow less than the minimum detectable concentration, and the distribution of tritium in groundwater at the INEL, aqueous disposal of tritium at the INEL has had no measurable effect on tritium concentrations in springflow from the Snake River Plain aquifer and in the Snake River near Buhl. 15 refs., 2 figs., 3 tabs

  7. World Antimalarial Resistance Network (WARN IV: Clinical pharmacology

    Directory of Open Access Journals (Sweden)

    Gbotosho Grace O

    2007-09-01

    Full Text Available Abstract A World Antimalarial Resistance Network (WARN database has the potential to improve the treatment of malaria, through informing current drug selection and use and providing a prompt warning of when treatment policies need changing. This manuscript outlines the contribution and structure of the clinical pharmacology component of this database. The determinants of treatment response are multi-factorial, but clearly providing adequate blood concentrations is pivotal to curing malaria. The ability of available antimalarial pharmacokinetic data to inform optimal dosing is constrained by the small number of patients studied, with even fewer (if any studies conducted in the most vulnerable populations. There are even less data relating blood concentration data to the therapeutic response (pharmacodynamics. By pooling all available pharmacokinetic data, while paying careful attention to the analytical methodologies used, the limitations of small (and thus underpowered individual studies may be overcome and factors that contribute to inter-individual variability in pharmacokinetic parameters defined. Key variables for pharmacokinetic studies are defined in terms of patient (or study subject characteristics, the formulation and route of administration of the antimalarial studied, the sampling and assay methodology, and the approach taken to data analysis. Better defining these information needs and criteria of acceptability of pharmacokinetic-pharmacodynamic (PK-PD studies should contribute to improving the quantity, relevance and quality of these studies. A better understanding of the pharmacokinetic properties of antimalarials and a more clear definition of what constitutes "therapeutic drug levels" would allow more precise use of the term "antimalarial resistance", as it would indicate when treatment failure is not caused by intrinsic parasite resistance but is instead the result of inadequate drug levels. The clinical pharmacology component

  8. Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

    Science.gov (United States)

    Karlsen Bjånes, Tormod; Mjåset Hjertø, Espen; Lønne, Lars; Aronsen, Lena; Andsnes Berg, Jon; Bergan, Stein; Otto Berg-Hansen, Grim; Bernard, Jean-Paul; Larsen Burns, Margrete; Toralf Fosen, Jan; Frost, Joachim; Hilberg, Thor; Krabseth, Hege-Merete; Kvan, Elena; Narum, Sigrid; Austgulen Westin, Andreas

    2016-01-01

    More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  9. Total and Available Heavy Metal Concentrations and Assessment of Soil Pollution Indices in Selected Soils of Zanjan

    Directory of Open Access Journals (Sweden)

    M. Taheri

    2017-01-01

    Full Text Available Introduction: Soil is a hardly renewable natural resource. Although soil degradation, caused by either human activities and natural processes is a relatively slow procedure, but its effects are long lasting and most often, irreversible in the time scale of man's life. Among the most significant soil contaminants resulting from both natural and human sources, heavy metals are more important due to their long- term toxicity effects. For evaluating soil's enrichment rate by heavy metals, a wide and full study of soils background values, including total and available fractions of heavy metal contents should be done. Zanjan province has some great mines and concentrating industries of lead and zinc especially in Angoran, Mahneshan. Unfortunately produced waste materials of these industries spread over the adjacent areas. Investigations showed that accumulation of some heavy metals in vegetables and crops planted in this region had occurred. Therefore, performing some investigations in these polluted areas and assessing pollution rate and heavy metals distribution in arable lands had prime importance. Our goals were: 1 determining the total and available amounts of Cu, Pb, Zn and Cd in the soils of arable lands in polluted areas of Zanjan city, 2 producing the distribution map for the metals mentioned above and 3 calculating pollution indices in the soils. Materials and Methods: The study area was in south west of Zanjan city. For soil sampling, a 1 Km by 1 Km grid defined in ArcGIS software on landuse layer and totally 144 points that placed on agricultural lands, due to our goals, were sampled. For sampling, in a 5m radius around the point we collected some subsamples from depth of 0 - 15 cm, and after mixing the subsamples, finally a 1Kg soil sample prepared and sent to the laboratory. Sampled soils were air dried and were passed through a 2mm sieve. Soils organic matter (OM content and texture were determined by Walkely-Black and Bouyoucos

  10. Accounting for genotype–by-environment interactions and non-additive genetic variation in genomic selection for water-soluble carbohydrate concentration in wheat

    Science.gov (United States)

    Abiotic stress tolerance traits are often complex and recalcitrant targets for conventional breeding improvement in many crop species. This study evaluated the potential of genomic selection to predict water-soluble carbohydrate concentration (WSCC), an important drought tolerance trait, in wheat un...

  11. Fuzzy pharmacology: theory and applications.

    Science.gov (United States)

    Sproule, Beth A; Naranjo, Claudio A; Türksen, I Burhan

    2002-09-01

    Fuzzy pharmacology is a term coined to represent the application of fuzzy logic and fuzzy set theory to pharmacological problems. Fuzzy logic is the science of reasoning, thinking and inference that recognizes and uses the real world phenomenon that everything is a matter of degree. It is an extension of binary logic that is able to deal with complex systems because it does not require crisp definitions and distinctions for the system components. In pharmacology, fuzzy modeling has been used for the mechanical control of drug delivery in surgical settings, and work has begun evaluating its use in other pharmacokinetic and pharmacodynamic applications. Fuzzy pharmacology is an emerging field that, based on these initial explorations, warrants further investigation.

  12. The pharmacology of gynaecology.

    Science.gov (United States)

    Tothill, A

    1980-09-01

    Focus in this discussion of the pharmacology of gynecology is on the following: vaginal infections; genital herpes; genital warts; pelvic inflammatory disease; urinary infections; pruritus vulvae; menstrual problems; infertility; oral contraception; and hormone replacement therapy. Doctors in England working in Local Authority Family Planning Clinics are debarred from prescribing, and any patient with a vaginal infection has to be referred either to a special clinic or to her general practitioner which is often preferable as her medical history will be known. Vaginal discharge is a frequent complaint, and it is necessary to obtain full details. 1 of the most common infections is vaginal candidosis. Nystatin pessaries have always been a useful 1st-line treatment and are specific for this type of infection. Trichomonas infection also occurs frequently and responds well to metronidazole in a 200 mg dosage, 3 times daily for 7 days. It is necessary to treat the consort at the same time. Venereal diseases such as syphilis and gonorrhea always require vigorous treatment. Patients are now presenting with herpes genitalis far more often. The only treatment which is currently available, and is as good as any, is the application of warm saline to the vaginal area. Genital warts may be discovered on routine gynecological examination or may be reported to the doctor by the patient. 1 application of a 20% solution of podophyllum, applied carefully to each wart, usually effects a cure. Pelvic inflammatory disease seems to be on the increase. Provided any serious disease is ruled out a course of systemic antibiotics is often effective. Urinary infections are often seen in the gynecologic clinic, and many of these will respond well to 2 tablets of co-trimoxazole, 2 times daily for 14 days. In pruritus vulvae it is important to determine whether the cause is general or local. Menstrual problems regularly occur and have been increased by the IUD and the low-dose progesterone pill

  13. Relationship between biomarker responses and contaminant concentration in selected tissues of flounder (Platichthys flesus from the Polish coastal area of the Baltic Sea

    Directory of Open Access Journals (Sweden)

    Magdalena Podolska

    2008-09-01

    Full Text Available Previous studies in the Gulf of Gdańsk discussed the responses of selected enzymatic biomarkers to the contaminant gradient in fish and mussels. In the present study, flounder muscle and liver tissues were analyzed for polychlorinated biphenyls (PCB congeners: 28, 52, 101, 118, 138, 153 and 180, organochlorine pesticides (HCHs, HCB and DDTs, and trace metals (Pb, Cd, Zn, Cu, Hg, Cr. An attempt was made to identify the relationship between the measured enzymatic biomarker responses (cholinesterases, malic enzyme, isocitrate dehydrogenase, glutathione S-transferase and contaminant concentrations in selected flounder tissues. The observed differences in enzymatic biomarker levels suggest that chronic exposure to low-concentration mixtures of contaminants may be occurring in the studied area. However, no conclusive evidence was found of a clear link between the biomarker responses and contaminant concentrations in flounder tissues.

  14. [Selective mutism].

    Science.gov (United States)

    Ytzhak, A; Doron, Y; Lahat, E; Livne, A

    2012-10-01

    Selective mutism is an uncommon disorder in young children, in which they selectively don't speak in certain social situations, while being capable of speaking easily in other social situations. Many etiologies were proposed for selective mutism including psychodynamic, behavioral and familial etc. A developmental etiology that includes insights from all the above is gaining support. Accordingly, mild language impairment in a child with an anxiety trait may be at the root of developing selective mutism. The behavior will be reinforced by an avoidant pattern in the family. Early treatment and followup for children with selective mutism is important. The treatment includes non-pharmacological therapy (psychodynamic, behavioral and familial) and pharmacologic therapy--mainly selective serotonin reuptake inhibitors (SSRI).

  15. Factors determining the concentration and chemical composition of particulate matter in the air of selected service facilities

    Science.gov (United States)

    Rogula-Kopiec, Patrycja; Pastuszka, Józef; Mathews, Barbara; Widziewicz, Kamila

    2018-01-01

    The link between increased morbidity and mortality and increasing concentrations of particulate matter (PM) resulted in great attention being paid to the presence and physicochemical properties of PM in closed rooms, where people spends most of their time. The least recognized group of such indoor environments are small service facilities. The aim of this study was to identify factors which determine the concentration, chemical composition and sources of PM in the air of different service facilities: restaurant kitchen, printing office and beauty salon. The average PM concentration measured in the kitchen was 5-fold (PM4, particle fraction ≥ 4 μm) and 5.3-fold (TSP, total PM) greater than the average concentration of these PM fractions over the same period. During the same measurement period in the printing office and in the beauty salon, the mean PM concentration was 10- and 4-fold (PM4) and 8- and 3-fold (TSP) respectively greater than the mean concentration of these PM fractions in outdoor air. In both facilities the main source of PM macro-components, especially organic carbon, were chemicals, which are normally used in such places - solvents, varnishes, paints, etc. The influence of some metals inflow from the outdoor air into indoor environment of those facilities was also recognized.

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

    Science.gov (United States)

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

    2010-07-01

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

  17. Pharmacological Aspects of Vipera xantina palestinae Venom

    Science.gov (United States)

    Momic, Tatjana; Arlinghaus, Franziska T.; Arien-Zakay, Hadar; Katzhendler, Jeoshua; Eble, Johannes A.; Marcinkiewicz, Cezary; Lazarovici, Philip

    2011-01-01

    In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integrin inhibitors. Viperistatin, a α1β1selective KTS disintegrin and VP12, a α2β1 selective C-type lectin were discovered. These snake venom proteins represent promising tools for research and development of novel collagen receptor selective drugs. These discoveries are also relevant for future improvement of antivenom therapy towards V.x.p. envenomation. PMID:22174978

  18. Influence of Select Antibiotics on Vibrio fischeri and Desmodesmus subspicatus at μg L-1 Concentrations.

    Science.gov (United States)

    de Vasconcelos, E C; Dalke, C R; de Oliveira, C M R

    2017-07-01

    The presence of pharmaceuticals in the aquatic environment is a contemporary reality and it is necessary to understand more about the effects of this presence on organisms. The purpose of this work was to assess the ecotoxicity of antibiotics metronidazole, nitrofurantoin, trimethoprim, and sulphamethoxazole (single and mixture) in Vibrio fischeri and Desmodesmus subspicatus at μg L -1 concentrations. The evaluation of the toxic effect of the antibiotics on V. fischeri and D. subspicatus was based on fluorescence and bioluminescence tests, respectively, using nominal concentrations. When tested individually, the four antibiotics gave rise to a toxic effect on the evaluated organisms. Sulphamethoxazole caused a higher toxic effect on V. fischeri and D. subspicatus from 7.81 to 500 μg L -1 . Trimethoprim and sulphamethoxazole showed hormesis for the concentrations, which ranged from 7.81 to 62.5 μg L -1 . The mixture of antibiotics induced a toxic effect on the V. fischeri and D. subspicatus organisms (from 0.03 to 1 μg L -1 concentrations) than when the antibiotics were evaluated individually. These results were significant since water quality problems are widespread all over the word, and emerging pollutants such as antibiotics have been detected in the aquatic environment in very low concentrations.

  19. Selective Recovery of Yttrium and Ytterbium Oxides from Abu Rusheid REEs Concentrate via Alkaline Leaching and Solvent Extraction

    International Nuclear Information System (INIS)

    El-Sheikh, E.M.

    2017-01-01

    The REEs concentrate prepared from Abu Rusheid lamprophyre ore material is found to assay 44.65% Y_2O_3 and 13.87% Yb_2O_3 together with less amounts of 10 other REEs. This concentrate has been subjected to alkaline leaching process using seven different alkali reagents (single or mixed). From the obtained results, the mixed Na_2CO_3/(NH_4)HCO_3 reagent has been able to leach up to 87.32 % of Yb and 98.73% of Y together with a minor amount of Eu( 1.44)%. Finally, TBP extractant has been used to separate highly pure Yb and Y concentrate oxides from the nitrate solution

  20. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

    to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...

  1. Short- and long-term temporal changes in soil concentrations of selected endocrine disrupting compounds (EDCs) following single or multiple applications of sewage sludge to pastures

    International Nuclear Information System (INIS)

    Rhind, S.M.; Kyle, C.E.; Ruffie, H.; Calmettes, E.; Osprey, M.; Zhang, Z.L.; Hamilton, D.; McKenzie, C.

    2013-01-01

    Temporal changes in soil burdens of selected endocrine disrupting compounds were determined following application to pasture of either sewage sludge or inorganic fertilizer. Soil polycyclic aromatic hydrocarbon and polychlorinated biphenyl concentrations were not altered. Changes in concentrations of diethylhexyl phthalate (DEHP) and PBDEs 47 and 99 differed with season but concentrations remained elevated for more than three weeks after application, when grazing animals are normally excluded from pasture. It is concluded that single applications of sewage sludge can increase soil concentrations of some, but not all classes of EDCs, possibly to concentrations sufficient to exert biological effects when different chemicals act in combination, but patterns of change depend on season and soil temperature. Analysis of soil from pasture subjected to repeated sludge applications, over 13 years, provided preliminary evidence of greater increases in soil burdens of all of the EDC groups measured, including all of the PBDE congeners measured. -- Highlights: •Sewage sludge or inorganic fertilizer was applied to pasture. •Soil PAH and PCB concentrations were not altered by sludge treatment. •Temporal changes in soil phthalate and PBDE differed with season. •Some soil EDC levels were elevated for more than three weeks after application. -- Effects of sewage sludge application to pastures on temporal changes in soil concentrations of endocrine disrupting compounds differ with chemical class and season

  2. Characteristic and Prediction of Carbon Monoxide Concentration using Time Series Analysis in Selected Urban Area in Malaysia

    Directory of Open Access Journals (Sweden)

    Abdul Hamid Hazrul

    2017-01-01

    Full Text Available Carbon monoxide (CO is a poisonous, colorless, odourless and tasteless gas. The main source of carbon monoxide is from motor vehicles and carbon monoxide levels in residential areas closely reflect the traffic density. Prediction of carbon monoxide is important to give an early warning to sufferer of respiratory problems and also can help the related authorities to be more prepared to prevent and take suitable action to overcome the problem. This research was carried out using secondary data from Department of Environment Malaysia from 2013 to 2014. The main objectives of this research is to understand the characteristic of CO concentration and also to find the most suitable time series model to predict the CO concentration in Bachang, Melaka and Kuala Terengganu. Based on the lowest AIC value and several error measure, the results show that ARMA (1,1 is the most appropriate model to predict CO concentration level in Bachang, Melaka while ARMA (1,2 is the most suitable model with smallest error to predict the CO concentration level for residential area in Kuala Terengganu.

  3. Technical basis for selecting radionuclide concentrations for use in Hanford tank basis for interim operation source term

    International Nuclear Information System (INIS)

    Cowley, W.L.

    1997-01-01

    This paper describes the development of a radiological source term for waste tanks at the Hanford Site Nuclear Reservation. It describes the methodology used to identify the most important radionuclides, determine appropriate concentrations, and define unit liter doses. An example of how unit liter doses are used is given

  4. Reduced Seminal Concentration of CD45pos Cells after Follicle-Stimulating Hormone Treatment in Selected Patients with Idiopathic Oligoasthenoteratozoospermia

    Directory of Open Access Journals (Sweden)

    Rosita A. Condorelli

    2014-01-01

    Full Text Available The present study evaluated the conventional sperm parameters and the seminal concentration of CD45pos cells (pan-leukocyte marker of infertile patients with idiopathic oligoasthenoteratozoospermia (OAT. The patients were arbitrarily divided into three groups treated with recombinant follicle-stimulating hormone FSH: α (Group A = 20 patients, recombinant FSH-β (Group B = 20 patients, and highly purified human FSH (Group C = 14 patients. All treated groups achieved a similar improvement of the main sperm parameters (density, progressive motility, and morphology, but only the increase in the percentage of spermatozoa with normal morphology was significant compared to the baseline in all three examined groups. Moreover, all groups had a significant reduction of the seminal concentration of CD45pos cells and of the percentage of immature germ cells. Before and after the treatment, the concentration of CD45pos cells showed a positive linear correlation with the percentage of immature germ cells and a negative correlation with the percentage of spermatozoa with regular morphology. These results demonstrate that treatment with FSH is effective in patients with idiopathic OAT and that there are no significant differences between the different preparations. The novelty of this study is in the significant reduction of the concentration of CD45pos cells observed after the treatment.

  5. Introducing enzyme selectivity as a quantitative parameter to describe the effects of substrate concentration on protein hydrolysis

    NARCIS (Netherlands)

    Butré, C.I.

    2014-01-01

    To understand the differences in peptide composition that result from variations in the conditions of enzymatic hydrolysis of proteins (e.g. substrate concentration) the mechanism of hydrolysis needs to be understood in detail. Therefore, methods and tools were developed to characterize and

  6. Evaluation of selected immunological parameters and the concentration of vitamin D in children with asthma. Case-control study

    Directory of Open Access Journals (Sweden)

    Agata Wawrzyniak

    2017-05-01

    Full Text Available Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled. Disease severity was assessed with the Asthma Control Test (ACT and spirometry. The control group consisted of 15 healthy children. Venous blood from each patient was collected on EDTA or on “clott”. Phenotypes of lymphocytes were evaluated by flow cytometry. Vitamin D concentration was assessed by chemiluminescent immunoassay (CLIA technology. There was a significant decrease in the percentage of T regulatory cells (p < 0.006 in children with asthma compared to the control group. There were no significant differences in the other investigated immunological parameters. In addition, in asthma group statistically significant decreased of vitamin D concentration (p < 0.04 was observed. There were also no significant correlations between vitamin D3 concentration and the course of asthma or percentage of regulatory cells. The results confirmed the role of regulatory T cells in the pathogenesis of asthma. Effects of vitamin D on the severity of the disease has not been proven.

  7. RNA sequencing based analysis of the spleen transcriptome following the infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations

    DEFF Research Database (Denmark)

    Hamzic, Edin; Kjærup, Rikke Brødsgaard; Mach, Núria

    2016-01-01

    in strategies to control IB. To this end, two chicken lines, selected for high and low serum concentration of mannose-binding lectin (MBL), a soluble pattern recognition receptor, were studied. In total, 32 animals from each line (designated L10H for high and L10L for low MBL serum concentration) were used....... Sixteen birds from each line were infected with IBV on day 1 and birds were euthanized at 1 week and 3 weeks post infection, 8 uninfected controls and 8 infected birds from each line at each occasion. RNA sequencing was performed on spleen samples from all 64 birds used in the experiment. Differential...

  8. Photosynthetic pigment concentrations, gas exchange and vegetative growth for selected monocots and dicots treated with two contrasting coal fly ashes

    Energy Technology Data Exchange (ETDEWEB)

    Yunusa, I.A.M.; Burchett, M.D.; Manoharan, V.; DeSilva, D.L.; Eamus, D.; Skilbeck, C.G. [University of Technology Sydney, Sydney, NSW (Australia). Dept. of Environmental Science

    2009-07-15

    There is uncertainty as to the rates of coal fly ash needed for optimum physiological processes and growth. In the current study we tested the hyothesis that photosynthetic pigments concentrations and CO{sub 2} assimilation (A) are more sensitive than dry weights in plants grown on media amended with coal fly ash. We applied the Terrestrial Plant Growth Test (Guideline 208) protocols of the Organization for Economic Cooperation and Development (OECD) to monocots (barley (Hordeum vulgare) and ryegrass (Secale cereale)) and dicots (canola (Brasica napus), radish (Raphanus sativus), field peas (Pisum sativum), and lucerne (Medicago sativa)) on media amended with fly ashes derived from semi-bituminous (gray ash) or lignite (red ash) coals at rates of 0, 2.5, 5.0, 10, or 20 Mg ha(-1). The red ash had higher elemental concentrations and salinity than the gray ash. Fly ash addition had no significant effect on germination by any of the six species. At moderate rates ({<=}10 Mg ha{sup -1}) both ashes increased (P < 0.05) growth rates and concentrations of chlorophylls a and b, but reduced carotenoid concentrations. Addition of either ash increased A in radish and transpiration in barley. Growth rates and final dry weights were reduced for all of the six test species when addition rates exceeded 10 Mg ha{sup -1} for gray ash and 5 Mg ha{sup -1} for red ash. We concluded that plant dry weights, rather than pigment concentrations and/or instantaneous rates of photosynthesis, are more consistent for assessing subsequent growth in plants supplied with fly ash.

  9. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.

    Science.gov (United States)

    Russo, Ethan B; Marcu, Jahan

    2017-01-01

    The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed "pharmacological treasure trove." © 2017 Elsevier Inc. All rights reserved.

  10. Effect of lactation stage on the concentration of essential and selected toxic elements in milk of Dubrovačka ruda - Croatian endangered breed

    Directory of Open Access Journals (Sweden)

    Zvonko Antunović

    2016-11-01

    Full Text Available The aim of the present study was to determine the lactation stage effect on the concentration of essential and selected toxic elements in the sheep’s milk of Dubrovačka ruda. The research was conducted with 23 sheep, average age of 4 years, of 3rd lactation, while the milk samples were taken during the early (60th day, middle (90th day and late (120th day lactation stage. The sheep were selected according to uniformed body development, adequate health status, body condition, equable age (4 years, parity (3rd lactation, stage of lactation (±7 days and litter size (single. Sheep were reared on the extensive Mediterranean pastures, reared indoors afterwards, fed with hay ad libitum and feed mixtures in average 0.5 kg/day. Milk sample was collected during morning milking from each sheep. The digested samples were analyzed with continuous flow hydride generation technique using inductively coupled plasma for Ca, Mg, K, P, Na, Cu, Fe, Zn, Mn, Ni, Mo, Co, Cr, Cd and Pb concentrations. Significant increase of Mg, Na, Se, Mn, Mo and Cd concentrations were found in milk as well as decrease of K concentration during the lactation. Although the concentration of Ca, Cu, Cr and As in milk during the lactation is increased, the differences between the lactation stages were not observed. Concentrations of P, Fe, Ni, Pb and Hg in milk of Dubrovačka ruda did not differ during the lactation. The low concentrations of Cr, Cd, Pb, As, Hg in milk indicate the safety for consumers and preserved environment of Dubrovnik-Neretva County.

  11. Effects of pH and pulp potential on the selective separation of Molybdenite from the Sungun Cu-Mo concentrate

    Directory of Open Access Journals (Sweden)

    Javad Mehrabani

    2017-12-01

    Full Text Available In this research, selective flotation of Mo from the Sungun Cu-Mo concentrate was evaluated in different operating conditions. It was found that the addition of 16 kg/t Na2S into flotation pulp and aeration decreased rapidly the initial oxidized- reduction potential (ORP of the pulp from +228mV to -597 mV (with reference to standard Ag/AgCl electrode and increasing the amount of Na2S by 50kg/t did not change the pulp potential. The highest metallurgical and selective separation of Mo from Mo-Cu concentrate were achieved at pH= 10.5 and ORP

  12. Electronic cigarettes and nicotine clinical pharmacology.

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-05-01

    To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

  13. Electronic cigarettes and nicotine clinical pharmacology

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  14. Effects of soil type and genotype on lead concentration in rootstalk vegetables and the selection of cultivars for food safety.

    Science.gov (United States)

    Ding, Changfeng; Zhang, Taolin; Wang, Xingxiang; Zhou, Fen; Yang, Yiru; Yin, Yunlong

    2013-06-15

    Lead (Pb) contamination of soil poses severe health risks to humans through vegetable consumption. The variations of Pb concentration in different parts of rootstalk vegetables (radish, carrot and potato) were investigated by using twelve cultivars grown in acidic Ferralsols and neutral Cambisols under two Pb treatments (125 mg kg(-1) and 250 mg kg(-1) for Ferralsols; 150 mg kg(-1) and 300 mg kg(-1) for Cambisols) in a pot experiment. The Pb concentration in edible parts was higher in Ferralsols under two Pb treatments, with range from 0.28 to 4.14, 0.42-10.66 mg kg(-1) (fresh weight) respectively, and all of them exceeded the food safety standard (0.1 mg kg(-1)) recommended by the Codex Alimentarius Commission of FAO and WHO. The Pb concentration in edible parts was significantly affected by genotype, soil type and the interaction between these two factors. The variation of Pb concentration in different cultivars was partially governed by Pb absorption and the transfer of Pb from aerial to edible part. The results revealed that caution should be paid to the cultivation of rootstalk vegetables in Pb-contaminated Ferralsols without any agronomic management to reduce Pb availability and plant uptake. For Cambisols with slight to moderate Pb contamination, growing potato cultivar Shandong No.1 and Chongqing No.1 was effective in reducing the risk of Pb entering human food chain. The results suggest the possibility of developing cultivar- and soil-specific planting and monitoring guidelines for the cultivation of rootstalk vegetables on slight to moderate Pb-contaminated soils. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Applicability Of A Semi-Automated Clinical Chemistry Analyzer In Determining The Antioxidant Concentrations Of Selected Plants

    OpenAIRE

    Allan L. Hilario; Phylis C. Rio; Geraldine Susan C. Tengco; Danilo M. Menorca

    2017-01-01

    Plants are rich sources of antioxidants that are protective against diseases associated to oxidative stress. There is a need for high throughput screening method that should be useful in determining the antioxidant concentration in plants. Such screening method should significantly simplify and speed up most antioxidant assays. This paper aimed at comparing the applicability of a semi-automated clinical chemistry analyzer Pointe Scientific MI USA with the traditional standard curve method and...

  16. Evaluation of selected immunological parameters and the concentration of vitamin D in children with asthma. Case-control study

    Science.gov (United States)

    Wawrzyniak, Agata; Lipińska-Opałka, Agnieszka; Zdanowski, Robert; Murawski, Piotr; Kalicki, Bolesław

    2017-01-01

    Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled. Disease severity was assessed with the Asthma Control Test (ACT) and spirometry. The control group consisted of 15 healthy children. Venous blood from each patient was collected on EDTA or on “clott”. Phenotypes of lymphocytes were evaluated by flow cytometry. Vitamin D concentration was assessed by chemiluminescent immunoassay (CLIA) technology. There was a significant decrease in the percentage of T regulatory cells (p asthma compared to the control group. There were no significant differences in the other investigated immunological parameters. In addition, in asthma group statistically significant decreased of vitamin D concentration (p asthma or percentage of regulatory cells. The results confirmed the role of regulatory T cells in the pathogenesis of asthma. Effects of vitamin D on the severity of the disease has not been proven. PMID:28680338

  17. Copper, cadmium, and zinc concentrations in aquatic food chains from the Upper Sacramento River (California) and selected tributaries

    Science.gov (United States)

    Saiki, M.K.; Castleberry, D. T.; May, T. W.; Martin, B.A.; Bullard, F. N.

    1995-01-01

    Metals enter the Upper Sacramento River above Redding, California, primarily through Spring Creek, a tributary that receives acid-mine drainage from a US EPA Superfund site known locally as Iron Mountain Mine. Waterweed (Elodea canadensis) and aquatic insects (midge larvae, Chironomidae; and mayfly nymphs, Ephemeroptera) from the Sacramento River downstream from Spring Creek contained much higher concentrations of copper (Cu), cadmium (Cd), and zinc (Zn) than did similar taxa from nearby reference tributaries not exposed to acid-mine drainage. Aquatic insects from the Sacramento River contained especially high maximum concentrations of Cu (200 mg/kg dry weight in midge larvae), Cd (23 mg/kg dry weight in mayfly nymphs), and Zn (1,700 mg/kg dry weight in mayfly nymphs). Although not always statistically significant, whole-body concentrations of Cu, Cd, and Zn in fishes (threespine stickleback, Gasterosteus aculeatus; Sacramento sucker, Catostomus occidentalis; Sacramento squawfish, Ptychocheilus grandis; and chinook salmon, Oncorhynchus tshawytasch) from the Sacramento River were generally higher than in fishes from the reference tributaries.

  18. Application of the Alternative Traditional and Selective Precipitation Routes for Recovery of High Grade Thorium Concentrates from Egyptian Crude Monazite Sand

    International Nuclear Information System (INIS)

    Helaly, O.S.

    2017-01-01

    Process flow sheet selection for thorium separation in relatively high grade concentrate from Egyptian crude monazite sand was carried out. Traditional selective leaching and precipitation routes were applied after sulfuric acid digestion upon Egyptian crude monazite for this purpose. The resultant hot grey sulfate paste from monazite digestion was firstly cooled to ambient temperature then leached by normal water into two successive stages. The first leach solution contained most of the thorium which represents about 88% of the present thorium and its concentration in the liquor reached 4.5 g Th/l. This liquor also contains most of the free acids and major of impurities especially iron (more than 6.3 g Fe/l). Different routes were tested to evaluate the suitable conditions that verify maximum recovery of thorium from such monazite sulfate solution and producing relatively high grade concentrate. Two different possible traditional and selective methods were involved, namely; thorium initial precipitation with rare earth elements as double sulfate or its precipitation as phosphate through acidity control at ph 1.1 which seems to be the simple, brief and convenient route to accomplish this purpose. Further separation and/or upgrading of thorium from these precipitates (after conversion to hydroxides or without) were conducted through re-dissolution in hydrochloric acid and re-precipitation with different selective reagents in the form of hydroxide, oxalate or fluoride was also included. The target was accomplished through thorium co-precipitation with light rare earth elements as double sulfate, followed by its recovery from this fraction, where a concentrate of grade 68.3% was produced

  19. A Flow System for Generation of Concentration Perturbation in Two-Dimensional Correlation Near-Infrared Spectroscopy: Application to Variable Selection in Multivariate Calibration

    OpenAIRE

    Pereira, CF; Pasquini, C

    2010-01-01

    A flow system is proposed to produce a concentration perturbation in liquid samples, aiming at the generation of two-dimensional correlation near-infrared spectra. The system presents advantages in relation to batch systems employed for the same purpose: the experiments are accomplished in a closed system; application of perturbation is rapid and easy; and the experiments can be carried out with micro-scale volumes. The perturbation system has been evaluated in the investigation and selection...

  20. Selection of representative calibration sample sets for near-infrared reflectance spectroscopy to predict nitrogen concentration in grasses

    DEFF Research Database (Denmark)

    Shetty, Nisha; Rinnan, Åsmund; Gislum, René

    2012-01-01

    ) algorithm were used and compared. Both Puchwein and CADEX methods provide a calibration set equally distributed in space, and both methods require a minimum prior of knowledge. The samples were also selected randomly using complete random, cultivar random (year fixed), year random (cultivar fixed......) and interaction (cultivar × year fixed) random procedures to see the influence of different factors on sample selection. Puchwein's method performed best with lowest RMSEP followed by CADEX, interaction random, year random, cultivar random and complete random. Out of 118 samples of the complete calibration set...... effectively enhance the cost-effectiveness of NIR spectral analysis by reducing the number of analyzed samples in the calibration set by more than 80%, which substantially reduces the effort of laboratory analyses with no significant loss in prediction accuracy....

  1. Selection of AT-Tank Analysis Equipment for Determining Completion of Mixing and Particle Concentration in Hanford Waste Tanks

    International Nuclear Information System (INIS)

    Dodson, M.G.; Ozanich, R.M.; Bailey, S.A.

    1999-01-01

    This document will describe the functions and requirements of the at-tank analysis system concept developed by the Robotics Technology Development Program (RTDP) and Berkeley Instruments. It will discuss commercially available at-tank analysis equipment, and compare those that meet the stated functions and requirements. This is followed by a discussion of the considerations used in the selection of instrumentation for the concept design, and an overall description of the proposed at-tank analysis system

  2. Nanofluidic Pre-Concentration Devices for Enhancing the Detection Sensitivity and Selectivity of Biomarkers for Human Performance Monitoring

    Science.gov (United States)

    2016-10-17

    antibody by glutaraldehyde coupling, for enabling the selective catalysis of α-naphthyl phosphate (NPP) to the electroactive α-naphthol (NP) product , as...solution at 4 °C overnight. The dialysis product , PSA antibody-ALP conjugate, was then transferred to an Eppendorf tube and mixed with an equal...volume of glycerin and 1% BSA, for storage at 0 °C, prior to the experiments. Cortisol, Triamcinolone, Estradiol, Testosterone and Progesterone were

  3. Contemporary pharmacological obesity treatments

    Directory of Open Access Journals (Sweden)

    Kaszubska Katarzyna

    2016-06-01

    Full Text Available In the last few years, obesity has become a global epidemic. Consequently, worldwide costs associated with managing obesity and obesity-related comorbidities are huge. Numerous studies have focused on discerning the appropriate proper treatment of weight related problems such as overweight and obesity. Moreover, many clinical trials have been conducted for many years in order to introduce effective anti-obesity drugs. The aim of the present review is to provide an overview of current and future pharmacotherapy for obesity, and to provide the reader with a determination of the concentration and composition of long and short term anti-obesity drugs, doing so by placing emphasis on pharmacotherapy and up-to-day solutions. It should be noted that, currently, the worldwide pharmacotherapy is represented by phendimetrazine, benzphetamine and diethylpropion, as well as by orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide. In our paper, individual cases of patients’ needs are thoroughly illustrated by way of examples. Medical prescriptions and contraindications are also described.

  4. Pharmacology of antihistamines

    Directory of Open Access Journals (Sweden)

    Martin K Church

    2013-01-01

    Full Text Available H 1- antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H 1 -receptors which are members of the G-protein family. The older first generation H 1- antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H 1 -antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.

  5. Selectivity of calixarene-bonded silica phases in HPLC: Description of special characteristics with a multiple term linear equation at different methanol concentrations.

    Science.gov (United States)

    Schneider, Christian; Jira, Thomas

    2010-10-01

    Retention and selectivity characteristics of different calixarene-, resorcinarene- and alkyl-bonded stationary phases are examined by analyzing a set of test solutes covering the main interactions (hydrophobic, steric, ionic, polar) that apply in HPLC. Therefore Dolan and Snyder's multiple term linear equation has been adapted to fit the properties of calixarene-bonded columns. The obtained parameters are used to describe retention and selectivity of the novel Caltrex(®) phases and to elucidate underlying mechanisms of retention. Here, differences of stationary phase characteristics at different methanol concentrations in the mobile phases are examined. Both selectivity and retention were found to depend on the methanol content. Differences of these dependencies were found for different stationary phases and interactions. The differences between common alkyl-bonded and novel calixarene-bonded phases increase with increasing methanol content.

  6. Accumulation of Mercury (Hg) and Methyl Mercury (Me Hg) Concentrations In Selected Marine Biota From Manjung Coastal Area

    International Nuclear Information System (INIS)

    Anisa Abdullah; Zaini Hamzah; Ahmad Saat; Ahmad Saat; Abd Khalik Wood; Masitah Alias

    2015-01-01

    Level of mercury (Hg) and methyl mercury (Me Hg) in marine ecosystem has been intensively studied as these toxic substances could be accumulated in the marine biota. This study is focusing on the Hg and Me Hg content in marine biota in Manjung coastal area. This area has high potential being affected by rapid socio-economic development of Manjung area such as heavy industrial activities (coal fired power plant, iron foundries, port development and factories), agricultural runoff, waste and toxic discharge, quarries, housing constructions. It may has a potential risk when released into the atmosphere and dispersed on the surface of water and continue deposited at the bottom of the water and sediment and being absorbed by marine biota. The concentrations of Hg and Me Hg in marine ecosystem can be adversely affect human health when it enters the food chain. In this study, five species of marine biota including Johnius dussumieri (Ikan Gelama), Pseudorhombus malayanus (Ikan Sebelah), Arius maculatus (Ikan Duri), Portunus pelagicus (Ketam Renjong) and Charybdis natator (Ketam Salib) were collected during rainy and dry seasons. Measurements were carried out using inductively coupled plasma mass spectrometry (ICP-MS) technique. The Hg concentrations for dry and rainy season are in the range 65.13-102.12 μg/ kg and 75.75-106.10 μg/ kg respectively, while for MeHg concentrations for dry and rainy seasons are in the range 4.35-6.26 μg/ kg and 5.42-6.46 μg/ kg, respectively. These results are below the limit set by Malaysia Food Act (1983). Generally, marine biota from the Manjung coastal area is safe to consume due to low value of ingestion dose rate and health risk index (HRI) for human health. (author)

  7. Concentration of PAHs in Municipal Wastewater in Selected Sewer Collectors of the Upper Silesian Urban Area, Poland

    Directory of Open Access Journals (Sweden)

    Pistelok Franciszek

    2014-12-01

    (GC-MS. The concentrations of 16 PAHs sum (EPA list ranged between 1.025 and 3.056 μg/L. Phenanthrene dominated in nearly all the analysed samples. The contents of PAHs, which are priority hazardous substances according to the directive, were high in the analysed samples. The obtained results and the analysis of diagnostic ratios for the emissions of PAHs into the air helped to reach the conclusion that traffic emissions were the main source of PAHs in the examined wastewater.

  8. Clinical pharmacology of homoharringtonine

    International Nuclear Information System (INIS)

    Savaraj, N.; Lu, K.; Dimery, I.; Feun, L.G.; Burgess, M.; Keating, M.; Loo, T.L.

    1986-01-01

    Clinical pharmacokinetics of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 mu Ci) by continuous 6-hour infusion. The drug and metabolites were quantified by radiochemical and high-performance liquid chromatographic techniques. Computerized nonlinear least-square regression and curve stripping were used to characterize HHT and total [ 3 H]HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an alpha-half-life of 0.5 +/- 0.1 hours and a beta-half-life of 9.3 +/- 1.4 hours. The total clearance of HHT was 177.4 +/- 27.7 ml X hour-1 X kg-1, and the apparent volume of distribution, estimated from the area under the drug concentration versus time curve, was 2.4 +/- 0.4 L X kg-1. Correspondingly, the total [ 3 H]HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total 3 H was 67.5 +/- 7.5 hours, 7.4 times longer; the total clearance was 30.9 +/- 3.1 ml X hour-1 X kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 +/- 0.1 L X kg-1, nearly the same. The 72-hour cumulative urinary excretion of total tritium was 28.2% of the administered dose and only 38.3% of this resided in unchanged HHT. Thus, urinary excretion was not a major route of elimination of HHT. Moreover, HHT underwent extensive metabolism; one major and two minor unidentified products were detected in both plasma and urine

  9. PHARMACOLOGY OF CANNABINOIDS

    Directory of Open Access Journals (Sweden)

    Ilonka Ferjan

    2015-06-01

    Full Text Available The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cells populations. The cannabinoids have been authorized for chemotherapy-induced nausea and vomiting; stimulation of appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. Isolation and identification of different cannabinoids from cannabis and synthesis of novel, more selective, derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoids formulations with unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects e. g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subject to the same regulations as other potential drugs. Safety and efficacy of any potential drug candidate, regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, as well as the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of "Remedium cardinale."

  10. Precision pharmacology for Alzheimer's disease.

    Science.gov (United States)

    Hampel, Harald; Vergallo, Andrea; Aguilar, Lisi Flores; Benda, Norbert; Broich, Karl; Cuello, A Claudio; Cummings, Jeffrey; Dubois, Bruno; Federoff, Howard J; Fiandaca, Massimo; Genthon, Remy; Haberkamp, Marion; Karran, Eric; Mapstone, Mark; Perry, George; Schneider, Lon S; Welikovitch, Lindsay A; Woodcock, Janet; Baldacci, Filippo; Lista, Simone

    2018-04-01

    The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses. Consequently, the distinct pattern of AD pathophysiology in space and time must be investigated on the basis of the individual biological makeup. This requires the implementation of systems biology and neurophysiology to facilitate Precision Medicine (PM) and Precision Pharmacology (PP). The regulation of several processes at multiple levels of complexity from gene expression to cellular cycle to tissue repair and system-wide network activation has different time delays (temporal scale) according to the affected systems (spatial scale). The initial failure might originate and occur at every level potentially affecting the whole dynamic interrelated systems within an organism. Unraveling the spatial and temporal dynamics of non-linear pathophysiological mechanisms across the continuum of hierarchical self-organized systems levels and from systems homeostasis to systems failure is key to understand AD. Measuring and, possibly, controlling space- and time-scaled adaptive and compensatory responses occurring during AD will represent a crucial step to achieve the capacity to substantially modify the disease course and progression at the best suitable timepoints, thus counteracting disrupting critical pathophysiological inputs. This approach will provide the conceptual basis for effective

  11. Imaging of dopamine release induced by pharmacologic and nonpharmacologic stimulations

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Technological advances in molecular imaging made it possible to image synaptic neurotransmitter concentration in living human brain. The dopaminergic system has been most intensively studied because of its importance in neurological as well as psychiatric disorders. This paper provides a brief overview of recent progress in imaging studies of dopamine release induced by pharmacologic and nonpharmacologic stimulations.

  12. Effect of exposure to hyperoxic, hypobaric, and hyperbaric environments on concentrations of selected and aerobic and anaerobic fecal flora of mice.

    Science.gov (United States)

    Gillmore, J D; Gordon, F B

    1975-03-01

    Alterations in selected aerobic and anaerobic fecal microflora of the mouse were determined during exposure to hyperoxic and normoxic hypo- and hyperbaric environments. Examination of fecal cultures obtained during exposure for 6 weeks to either 60 or 77% oxygen concentration 1 atmosphere absolute revealed little alteration in the aerobic or anaerobic flora. There appeared to be only a retardation in the reduction of the Klebsiella-Enterobacter flora which normally occurs after weaning. During exposure to hypobaric environments (100% O-2, 0.2 atmosphere absolute), significant alterations in concentrations of Escherichia coli, slow lactose fermenters, Klebsiella-Enterobacter, and enterococci were found in some instances. All alterations were toward increased concentrations. Variations in concentrations of different colony types of obligately anaerobic gram-positive (anGPR) and gram-negative (anGNR) rods cultured during the same experiments also occurred. One colony type of anGPR appeared to decrease while a second type increased in numbers. Concentrations of three colony types of anGNR were generally, but not always, increased. During hyperbaric exposure (2.8% O-2, 7.5 atmospheres absolute), increased concentrations of Klebsiella-Enterobacter, E. coli, slow lactose fermenters and enterococci were also noted. Changes in numbers of both colony types of anGPR, when occurring, were in the direction of lower numbers. Alteration in numbers of anGNR were in both directions but were more frequent in the direction of higher numbers. After return to normal air for 4 weeks of either hypo- or hyperbaric exposure, fecal concentrations of all organisms tended to revert toward control values with the exception of the anGPR which remained in lower concentrations after termination of the hyperbaric exposure. These observations indicate that, despite the great variation in the fecal flora among individual mice, it is possible to discover the effects induced by altered gaseous

  13. Control of oxygen vacancies and Ce+3 concentrations in doped ceria nanoparticles via the selection of lanthanide element

    International Nuclear Information System (INIS)

    Shehata, N.; Meehan, K.; Hudait, M.; Jain, N.

    2012-01-01

    The effect of lanthanides that have positive association energies with oxygen vacancies, such as samarium and neodymium, and the elements with negative association energies, such as holmium and erbium, on ionization state of cerium and, consequentially, the oxygen vacancy concentration in doped ceria nanoparticles are investigated in this article. Structural and optical characterizations of the doped and undoped ceria nanoparticles, synthesized using chemical precipitation, are carried out using transmission electron microscopy, X-ray diffractometry, optical absorption spectroscopy, and fluorescence spectroscopy. It is deduced that the negative association energy dopants decrease the conversion of Ce +4 into Ce +3 and, hence, scavenge the oxygen vacancies, evidenced by the observed increase in the allowed direct bandgap, decrease in the integrated fluorescence intensity, and increased the size of doped nanoparticles. The opposite trends are obtained when the positive association dopants are used. It is concluded that the determining factor as to whether a lanthanide dopant in ceria acts as a generator or scavenger of oxygen vacancies in ceria nanoparticles is the sign of the association energy between the element and the oxygen vacancies. The ability to tailor the ionization state of cerium and the oxygen vacancy concentration in ceria has applications in a broad range of fields, which include catalysis, biomedicine, electronics, and environmental sensing.

  14. Uranium concentrations in lake and stream waters and sediments from selected sites in the Susitna River Basin, Alaska

    International Nuclear Information System (INIS)

    Hill, D.E.

    1977-03-01

    During the summer of 1976, 141 water and 211 sediment samples were taken from 147 locations in the Susitna River basin in Alaska by the Geophysical Institute of the University of Alaska for the LASL. These samples were taken to provide preliminary information on the uranium concentrations in waters and sediments from the Susitna River basin and to test the analytical methods proposed for the NURE Hydrogeochemical and Stream Sediment Reconnaissance for uranium in Alaska. The uranium determinations resulting from the fluorometric analysis of the water samples and the delayed-neutron counting of the sediment samples are presented. The low levels of uranium in the water samples, many of which were below the detectable limit of the LASL fluorometric technique, indicate that a more sensitive analytical method is needed for the analysis of Alaskan water samples from this area. An overlay showing numbered sample locations and overlays graphically portraying the concentrations of uranium in the water and sediment samples, all at 1:250,000 scale for use with existing USGS topographic sheets, are also provided as plates

  15. Studies on rheological and leaching characteristics of heavy metals through selective additive in high concentration ash slurry.

    Science.gov (United States)

    Senapati, P K; Mohapatra, R; Pani, G K; Mishra, B K

    2012-08-30

    The generation and disposal level of thermal power plant ash in India is a challenging task. The conventional mode of dilute phase ash slurry (10-20% solids by weight) transport through pipelines being practiced in majority of these plants not only consumes huge amount of precious water and pumping energy but also causes serious environmental problem at the disposal site. The present study investigates the rheological and leaching characteristics of an Indian ash samples at high solids concentrations (>50% by weight) using sodium silicate as an additive. The flow behaviour of ash slurry in the concentration range of 50-60% by weight is described by a Bingham-plastic model. It was indicated that the addition of sodium silicate (0.2-0.6% of the total solids) could able to reduce both the slurry viscosity and the yield stress. The analysis of the ash samples for the presence of heavy metals such as Fe, Cd, Ni, Pb, Zn, Cu, Co, As and Hg were carried out following Hansen and Fisher procedure. The addition of sodium silicate affected the leaching characteristics of the ash samples over a period of 300 days resulting in the reduction of leaching of heavy metals. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Pharmacology Experiments on the Computer.

    Science.gov (United States)

    Keller, Daniel

    1990-01-01

    A computer program that replaces a set of pharmacology and physiology laboratory experiments on live animals or isolated organs is described and illustrated. Five experiments are simulated: dose-effect relationships on smooth muscle, blood pressure and catecholamines, neuromuscular signal transmission, acetylcholine and the circulation, and…

  17. Pharmacology of Marihuana (Cannabis sativa)

    Science.gov (United States)

    Maickel, Roger P.

    1973-01-01

    A detailed discussion of marihuana (Cannabis sativa) providing the modes of use, history, chemistry, and physiologic properties of the drug. Cites research results relating to the pharmacologic effects of marihuana. These effects are categorized into five areas: behavioral, cardiovascular-respiratory, central nervous system, toxicity-toxicology,…

  18. Chemotaxonomy and pharmacology of Gentianaceae

    DEFF Research Database (Denmark)

    Jensen, Søren Rosendal; Schripsema, Jan

    2002-01-01

    the remaining six are members of the Gentianeae. Based on the above results, a tentative list of chemical characteristics for the tribes of the Gentianaceae is presented. Finally, some pharmacologically interesting properties of plant extracts or compounds from taxa within Gentianaceae are listed....

  19. The determination of minimum inhibitory concentrations of selected antimicrobials for porcine Haemophilus parasuis isolates from the Czech Republic

    Directory of Open Access Journals (Sweden)

    Kateřina Nedbalcová

    2017-01-01

    Full Text Available Haemophilus parasuis isolates obtained from pigs in the Czech Republic were tested for their susceptibility to amoxicillin, penicillin, ceftiofur, enrofloxacin, tetracycline, and tulathromycin by determination of minimum inhibitory concentrations using the broth microdilution method. The H. parasuis isolates were mostly susceptible to majority of tested antimicrobials (amoxicillin 90%, penicillin 73.3%, enrofloxacin 83.3%, and tulathromycin 83.3%. All isolates were susceptible to ceftiofur. On the other hand, no isolate was susceptible to tetracycline, 30% of tested isolates were intermediately susceptible, and 70% were resistant. These findings indicate that tested antimicrobials with the exception of tetracycline should be the preferred option used for the treatment of infection caused by H. parasuis but due to the potential transmission of resistance from animals to humans, the use of ceftiofur is considered as a last resort option in antimicrobial treatment of animals.

  20. Tangential Flow Ultrafiltration: A “Green” Method for the Size Selection and Concentration of Colloidal Silver Nanoparticles

    Science.gov (United States)

    Anders, Catherine B.; Baker, Joshua D.; Stahler, Adam C.; Williams, Austin J.; Sisco, Jackie N.; Trefry, John C.; Wooley, Dawn P.; Pavel Sizemore, Ioana E.

    2012-01-01

    Nowadays, AgNPs are extensively used in the manufacture of consumer products,1 water disinfectants,2 therapeutics,1, 3 and biomedical devices4 due to their powerful antimicrobial properties.3-6 These nanoparticle applications are strongly influenced by the AgNP size and aggregation state. Many challenges exist in the controlled fabrication7 and size-based isolation4,8 of unfunctionalized, homogenous AgNPs that are free from chemically aggressive capping/stabilizing agents or organic solvents.7-13 Limitations emerge from the toxicity of reagents, high costs or reduced efficiency of the AgNP synthesis or isolation methods (e.g., centrifugation, size-dependent solubility, size-exclusion chromatography, etc.).10,14-18 To overcome this, we recently showed that TFU permits greater control over the size, concentration and aggregation state of Creighton AgNPs (300 ml of 15.3 μg ml-1 down to 10 ml of 198.7 μg ml-1) than conventional methods of isolation such as ultracentrifugation.19 TFU is a recirculation method commonly used for the weight-based isolation of proteins, viruses and cells.20,21 Briefly, the liquid sample is passed through a series of hollow fiber membranes with pore size ranging from 1,000 kD to 10 kD. Smaller suspended or dissolved constituents in the sample will pass through the porous barrier together with the solvent (filtrate), while the larger constituents are retained (retentate). TFU may be considered a "green" method as it neither damages the sample nor requires additional solvent to eliminate toxic excess reagents and byproducts. Furthermore, TFU may be applied to a large variety of nanoparticles as both hydrophobic and hydrophilic filters are available. The two main objectives of this study were: 1) to illustrate the experimental aspects of the TFU approach through an invited video experience and 2) to demonstrate the feasibility of the TFU method for larger volumes of colloidal nanoparticles and smaller volumes of retentate. First

  1. Airborne pollutant concentrations and health risks in selected Apulia region (IT) areas: preliminary results from the Jonico-Salentino project

    Science.gov (United States)

    Buccolieri, Riccardo; Genga, Alessandra; De Donno, Antonella; Siciliano, Tiziana; Siciliano, Maria; Serio, Francesca; Grassi, Tiziana; Rispoli, Gennaro; Cavaiola, Mattia; Lionello, Piero

    2017-04-01

    The Jonico-Salentino project (PJS) is a multidisciplinary study funded by Apulia Region (Det. N. 188_RU - 10/11/2015) aiming to assess health risk of people living in the cities of Lecce, Brindisi and Taranto. Citizens are exposed to emissions from industrial sources, biomass burning, vehicular, naval and air traffic, as well as from natural radioactive sources (radon). In this context, this work presents some preliminary results obtained by the Unit of University of Salento (Lecce) during an experimental campaign carried out in the study areas. The campaign is devoted to (i) sample particulate matter (PM), (ii) measure micro-meteorological variables and (iii) evaluate exposure levels of residents to main pollutants. Specifically, PM is sampled using a low volume sampler, while meteorological variables (wind speed components and direction temperature, relative humidity, precipitation and global solar radiation) are measured by advanced instrumentation such as ultrasonic anemometers which allows for the estimation of turbulence fluxes. The early effects of exposure to air pollutants is evaluated by the frequency of micronucleus (a biomarker of DNA damage) in exfoliated buccal cells collected using a soft-bristled toothbrush from oral mucosa of primary school children enrolled in the study. PM concentration data collected during the campaign are characterised from a chemical and morphological point of view; the analysis of different groups of particles allows identifying different natural and anthropogenic emission sources. This is done in conjunction to the investigation of the influence of local meteorology to elucidate the contribution of specific types of sources on final concentration levels. Finally, all data are used to assess the health risk of people living in the study areas as consequence of exposure to airborne pollutants.

  2. Applicability Of A Semi-Automated Clinical Chemistry Analyzer In Determining The Antioxidant Concentrations Of Selected Plants

    Directory of Open Access Journals (Sweden)

    Allan L. Hilario

    2017-07-01

    Full Text Available Plants are rich sources of antioxidants that are protective against diseases associated to oxidative stress. There is a need for high throughput screening method that should be useful in determining the antioxidant concentration in plants. Such screening method should significantly simplify and speed up most antioxidant assays. This paper aimed at comparing the applicability of a semi-automated clinical chemistry analyzer Pointe Scientific MI USA with the traditional standard curve method and using a Vis spectrophotometer in performing the DPPH assay for antioxidant screening. Samples of crude aqueous leaf extract of kulitis Amaranthus viridis Linn and chayote Sechium edule Linn were screened for the Total Antioxidant Concentration TAC using the two methods. Results presented in mean SD amp956gdl were compared using unpaired Students t-test P0.05. All runs were done in triplicates. The mean TAC of A. viridis was 646.0 45.5 amp956gdl using the clinical chemistry analyzer and 581.9 19.4 amp956gdl using the standard curve-spectrophotometer. On the other hand the mean TAC of S. edule was 660.2 35.9 amp956gdl using the semi-automated clinical chemistry analyzer and 672.3 20.9 amp956gdl using the spectrophotometer. No significant differences were observed between the readings of the two methods for A. viridis P0.05 and S. edible P0.05. This implies that the clinical chemistry analyzer can be an alternative method in conducting the DPPH assay to determine the TAC in plants. This study presented the applicability of a semi-automated clinical chemistry analyzer in performing the DPPH assay. Further validation can be conducted by performing other antioxidant assays using this equipment.

  3. Concentrations and geographical variations of selected toxic elements in meat from semi-domesticated reindeer (Rangifer tarandus tarandus L.) in mid- and northern Norway: evaluation of risk assessment.

    Science.gov (United States)

    Hassan, Ammar Ali; Brustad, Magritt; Sandanger, Torkjel M

    2012-05-01

    Meat samples (n = 100) from semi-domesticated reindeer (Rangifer tarandus tarandus L.) were randomly collected from 10 grazing districts distributed over four Norwegian counties in 2008 and 2009. The main aim was to study concentrations and geographical variations in selected toxic elements; cadmium (Cd), lead (Pb), arsenic (As), copper (Cu), nickel (Ni) and vanadium (V) in order to assess the risk associated with reindeer meat consumption. Sample solutions were analysed using an inductively coupled plasma high resolution mass spectrometer (ICP-HRMS), whereas analysis of variance (ANOVA) was used for statistical analyses. Geographical variations in element concentrations were revealed, with As and Cd demonstrating the largest geographical differences. No clear geographical gradient was observed except for the east-west downward gradient for As. The As concentrations were highest in the vicinity of the Russian border, and only Cd was shown to increase with age (p < 0.05). Sex had no significant effect on the concentration of the studied elements. The concentrations of all the studied elements in reindeer meat were generally low and considerably below the maximum levels (ML) available for toxic elements set by the European Commission (EC). Thus, reindeer meat is not likely to be a significant contributor to the human body burden of toxic elements.

  4. Chlorophenol and alkylphenol concentrations in sediment and mussel tissues collected from selected locations in Kentucky Lake, USA

    Energy Technology Data Exchange (ETDEWEB)

    Loganathan, B.; Brown, B.; Owen, D. [Murray State Univ., Murray, KY (United States); Sajwan, K. [Savannah State Univ., Savannah, GA (United States)

    2004-09-15

    Kentucky (KY) Lake is one the major human-constructed lakes in the US. It serves as an ultimate repository of substances entering this watershed from portions of seven southeastern states, which include a sizeable fraction of the U.S. chemical processing, agricultural chemical products and electronics manufacturing industries. Although a few studies have examined the levels of chlorinated organics in the KY Lake and the lowermost Tennessee River, there have been no reports on the distribution on the levels of chlorophenols and alkylphenols in sediment and/or biological tissues from this region. In this study, sediment, and freshwater mussels were collected from selected locations in KY Lake and Lake Barkley and analyzed for CPs and APs. Furthermore, wood samples from abandoned docks, navigational towers and wood found in the lake bottom were also analyzed to examine the sources of CPs to the lakes.

  5. Cadmium toxicity induced contrasting patterns of concentrations of free sarcosine, specific amino acids and selected microelements in two Noccaea species.

    Science.gov (United States)

    Zemanová, Veronika; Pavlík, Milan; Pavlíková, Daniela

    2017-01-01

    Cadmium (Cd) toxicity affects numerous metabolic processes in plants. In the presence of Cd, plants accumulate specific amino acids which may be beneficial to developing Cd tolerance. Our study aimed to characterize the changes in the metabolism of selected free amino acids that are associated with Cd tolerance, and investigate the levels of selected microelements in order to relate these changes to the adaptation strategies of two metallophytes-Noccaea caerulescens (Redlschlag, Austria) and Noccaea praecox (Mežica, Slovenia). The plants were exposed to Cd contamination (90 mg Cd/kg soil) for 120 days in a pot experiment. Our results showed higher Cd accumulation in N. praecox compared to N. caerulescens. Cadmium contamination reduced the zinc and nickel levels in both species and a mixed effect was determined for copper and manganese content. Differences in free amino acid metabolism were observed between the two metallophytes growing under Cd-free and Cd-loaded conditions. Under Cd-free conditions, aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) were accumulated more in the leaves of N. praecox than in N. caerulescens. Cd stress increased the content of these amino acids in both species but this increase was significant only in N. caerulescens leaves. Marked differences in the responses of the two species to Cd stress were shown for alanine, phenylalanine, threonine and sarcosine. Cadmium contamination also induced an increase of threonine as alanine and sarcosine decrease, which was larger in N. caerulescens than in N. praecox. All these factors contribute to the higher adaptation of N. praecox to Cd stress.

  6. Prophylactic treatment of migraine in children. Part 1. A systematic review of non-pharmacological trials

    NARCIS (Netherlands)

    Damen, L; Bruijn, J; Koes, BW; Berger, MY; Passchier, J; Verhagen, AP

    The aim of this study was to assess the efficacy of non-pharmacological prophylactic treatments of migraine in children. Databases were searched from inception to June 2004 and references were checked. We selected controlled trials reporting the effects of non-pharmacological prophylactic treatments

  7. Trace element, semivolatile organic, and chlorinated organic compound concentrations in bed sediments of selected streams at Fort Gordon, Georgia, February-April 2010

    Science.gov (United States)

    Thomas, Lashun K.; Journey, Celeste A.; Stringfield, Whitney J.; Clark, Jimmy M.; Bradley, Paul M.; Wellborn, John B.; Ratliff, Hagan; Abrahamsen, Thomas A.

    2011-01-01

    A spatial survey of streams was conducted from February to April 2010 to assess the concentrations of major ions, selected trace elements, semivolatile organic compounds, organochlorine pesticides, and polychlorinated biphenyls associated with the bed sediments of surface waters at Fort Gordon military installation near Augusta, Georgia. This investigation expanded a previous study conducted in May 1998 by the U.S. Geological Survey, in cooperation with the U.S. Department of the Army Environmental and Natural Resources Management Office of the U.S. Army Signal Center and Fort Gordon, that evaluated the streambed sediment quality of selected surface waters at Fort Gordon. The data presented in this report are intended to help evaluate bed sediment quality in relation to guidelines for the protection of aquatic life, and identify temporal trends in trace elements and semivolatile organic compound concentrations at streambed sites previously sampled. Concentrations of 34 major ions and trace elements and 102 semivolatile organic, organochlorine pesticide, and polychlorinated biphenyl compounds were determined in the fine-grained fraction of bed sediment samples collected from 13 of the original 29 sites in the previous study, and 22 additional sites at Fort Gordon. Three of the sites were considered reference sites as they were presumed to be located away from potential sources of contaminants and were selected to represent surface waters flowing onto the fort, and the remaining 32 nonreference sites were presumed to be located within the contamination area at the fort. Temporal trends in trace elements and semivolatile organic compound concentrations also were evaluated at 13 of the 32 nonreference sites to provide an assessment of the variability in the number of detections and concentrations of constituents in bed sediment associated with potential sources, accumulation, and attenuation processes. Major ion and trace element concentrations in fine-grained bed

  8. New approaches in analyzing the pharmacological properties of herbal extracts.

    Science.gov (United States)

    Hamburger, Matthias

    2007-01-01

    Herbal extracts are widely used and accepted in the population. The pharmacological characterization of such products meets some specific challenges, given the chemical complexity of the active ingredient. An overview is given on modern methods and approaches that can be used for that purpose. In particular, HPLC-based activity profiling is discussed as a means to identify pharmacologically active compounds in an extract, and expression profiling is described as a means for global assessment of effects exerted by multi-component mixtures such as extracts. These methods are illustrated with selected axamples from our labs, including woad (Isatis tinctoria), the traditional Chinese herb Danshen (Salvia miltiorrhiza) and black cohosh (Cimicifuga racemosa).

  9. Evaluation of the concentrations and distribution of carbonyl compounds in selected areas of a Brazilian bus terminal.

    Science.gov (United States)

    de Mendonça Ochs, Soraya; de Almeida Furtado, Leonardo; Pereira Netto, Annibal Duarte

    2015-06-01

    This study describes the determination of 30 carbonyl compounds (CCs) in three areas (bus boarding platform, passenger circulation area, and a pastry shop) of the Presidente João Goulart Bus Terminal, located at Niterói City, RJ, Brazil, and in an open area 700 m distant from the terminal. Samples were collected using SEP-PAK cartridges impregnated with 2,4-dinitrophenylhydrazine, during May to July 2012. The hydrazones formed were analyzed using rapid resolution liquid chromatography with UV detection. The studied locations showed distinct profiles of distribution of CC. The circulation area, which is influenced by different pollution sources, presented an intermediate profile between that of the pastry shop and boarding platform. Formaldehyde and acetaldehyde were the most abundant CC, but acetaldehyde predominated in the pastry shop once it is a by-product of baking yeast fermentation. Samples taken in the pastry shop and circulation area showed significant concentrations of hexanaldehyde and nonanaldehyde emitted during cooking. The pastry shop showed the largest level of total CC among the studied areas followed by the circulation area, the boarding platform, and the open area.

  10. Elemental concentration in hair and nail from a selected population group in the Machakos District of Keyna

    International Nuclear Information System (INIS)

    Otham, I.; Spyrou, N.M.

    1979-01-01

    Hair and nail samples were collected in the Iveti location of the Machakos District, Kenya by the University of Surrey Africa Study Group. The population chosen was one suggested by the World Health Organization because a large section of it is involved in agricultural activities, and it is supposedly free from industrial effluents. Also, since the District is where the 4th-year Nairobi medical students do their field training, health profiles may be more readily obtained. It was hoped that the study would yield normal ranges of elements for this population and provide information about their environment. Results for the concentrations of 11 elements (Na, Mg, Cl, Ca, V, Mn, Cu, Br, Sr, Ba and Hg) in hair and toe-nails obtained by instrumental neutron activation analysis for about one quarter (71 subjects) of the total 'normal' sample, divided by sex and age into four groups, are presented. These are treated as preliminary findings. In addition, the use of techniques in electron microscopy is advocated and discussed in evaluating hair and nails as indicators of environmental health. (author)

  11. Trace Element Concentration and Speciation in Selected Mining-Contaminated Soils and Water in Willow Creek Floodplain, Colorado

    Directory of Open Access Journals (Sweden)

    R. Burt

    2011-01-01

    Full Text Available Long-term mining activities in the mountains around Creede, Colorado have resulted in significant contamination in soils and water in the Willow Creek floodplain. Total major and trace were determined for soils and water and sequential chemical extraction for soils. Objectives were to determine concentrations and potential reactivity of trace elements and investigate their relationship with other soil and water properties. Water trace elements showed significant variability among sites, ranging from 347 to 12108 μg/L. Relative trend showed (Zn > Sr > Ba > (Mn > W > Cd > (Sn > V ≈ Ni ≈ Cu > Co > (Ag. Soil trace elements showed significant short-range spatial variability, ranging from 2819 to 19274 mg/kg. Relative trend showed (Pb ≈ Zn > Mn > Ba > P > (As > Cu > Sr > V > Cd > Sb ≈ Ag > (Co ≈ Cr > Mo ≈ Sn ≈ Ni > (Be ≈ W > Se ≈ Hg. Predominant fractions were oxide, specifically-sorbed/carbonate bound, and residual. Water soluble and exchangeable fractions showed (Zn ≈ Cd > Pb and Cd > Zn > Pb, respectively. Mobility factors for highly contaminated soils showed Cd ≈ Zn > Pb > Cu > As.

  12. High performance and thermally stable tandem solar selective absorber coating for concentrated solar thermal power (CSP) application

    Science.gov (United States)

    Prasad, M. Shiva; Kumar, K. K. Phani; Atchuta, S. R.; Sobha, B.; Sakthivel, S.

    2018-05-01

    A novel tandem absorber system (Mn-Cu-Co-Ox-ZrO2/SiO2) developed on an austenitic stainless steel (SS-304) substrate to show an excellent optical performance (αsol: 0.96; ɛ: 0.23@500 °C). In order to achieve this durable tandem, we experimented with two antireflective layers such as ZrO2-SiO2 and nano SiO2 layer on top of Mn-Cu-Co-Ox-ZrO2 layer. We optimized the thickness of antireflective layers to get good tandem system in terms of solar absorptance and emittance. Field emission scanning electron microscopy (FESEM), UV-Vis-NIR and Fourier transform infrared spectroscopy (FTIR) were used to characterize the developed coatings. Finally, the Mn-Cu-Co-Ox-ZrO2/SiO2 exhibits high temperature resistance up to 800 °C, thus allow an increase in the operating temperature of CSP which may lead to high efficiency. We successfully developed a high temperature resistant tandem layer with easy manufacturability at low cost which is an attractive candidate for concentrated solar power generation (CSP).

  13. Selective fermentation of pitted dates by S. cerevisiae for the production of concentrated fructose syrups and ethanol

    International Nuclear Information System (INIS)

    Putra, Meilana Dharma; Abasaeed, Ahmed E; Zeinelabdeen, Mohamed A; Gaily, Mohamed H; Sulieman, Ashraf K

    2014-01-01

    About half of worldwide production of dates is unconsumed. Dates contain over 75 % reduced sugars (mostly glucose and fructose with nearly equal amount). Compared to the commercial Saccharomyces cerevisiae wild strain, the strains ATCC 36858 and 36859 could produce high concentration fructose syrups. The fructose fractions obtained were 95.9 and 97.4% for ATCC 36858 and 86.5 and 91.4% for ATCC 36859 at 30 and 33°C, respectively. Fructose yields higher than 90% were obtained using ATCC 36858 compared to those obtained using ATCC 36859 which were 87.3 and 66.1% at 30 and 33°C, respectively. The ethanol yield using ATCC 36858 was higher than that using ATCC 36859 by 16 and 9% at 30 and 33°C, respectively. Through this finding, the production of fructose and ethanol from date extract is a promising process. Moreover, the fructose fractions obtained here (about 90%) are much higher than those obtained with the commercial process, i.e. 55 % fructose syrups.

  14. Selective fermentation of pitted dates by S. cerevisiae for the production of concentrated fructose syrups and ethanol

    Science.gov (United States)

    Dharma Putra, Meilana; Abasaeed, Ahmed E.; Zeinelabdeen, Mohamed A.; Gaily, Mohamed H.; Sulieman, Ashraf K.

    2014-04-01

    About half of worldwide production of dates is unconsumed. Dates contain over 75 % reduced sugars (mostly glucose and fructose with nearly equal amount). Compared to the commercial Saccharomyces cerevisiae wild strain, the strains ATCC 36858 and 36859 could produce high concentration fructose syrups. The fructose fractions obtained were 95.9 and 97.4% for ATCC 36858 and 86.5 and 91.4% for ATCC 36859 at 30 and 33°C, respectively. Fructose yields higher than 90% were obtained using ATCC 36858 compared to those obtained using ATCC 36859 which were 87.3 and 66.1% at 30 and 33°C, respectively. The ethanol yield using ATCC 36858 was higher than that using ATCC 36859 by 16 and 9% at 30 and 33°C, respectively. Through this finding, the production of fructose and ethanol from date extract is a promising process. Moreover, the fructose fractions obtained here (about 90%) are much higher than those obtained with the commercial process, i.e. 55 % fructose syrups.

  15. Pharmacological modulation of mitochondrial calcium homeostasis.

    Science.gov (United States)

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  16. Detailed characterization of the in vitro pharmacological and pharmacokinetic properties of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (25CN-NBOH), a highly selective and brain-penetrant 5-HT2A receptor agonist

    DEFF Research Database (Denmark)

    Jensen, Anders A; McCorvy, John D; Petersen, Sebastian Leth

    2017-01-01

    ]ketanserin/[3H]mesulergine, [3H]LSD and [3H]Cimbi-36 binding assays (Ki 2C/Ki 2A ratio range 52-81, Ki 2B/Ki 2A ratio 37). Moreover, in inositol phosphate and intracellular Ca2+ mobilization assays 25CN-NBOH exhibited 30- to 180-fold 5-HT2A/5-HT2C selectivities and 54-fold 5-HT2A/5-HT2B selectivity as measured...

  17. The major/minor concept: dependence of the selectivity of homogeneously catalyzed reactions on reactivity ratio and concentration ratio of the intermediates.

    Science.gov (United States)

    Schmidt, Thomas; Dai, Zhenya; Drexler, Hans-Joachim; Hapke, Marko; Preetz, Angelika; Heller, Detlef

    2008-07-07

    The homogeneously catalyzed asymmetric hydrogenation of prochiral olefins with cationic Rh(I) complexes is one of the best-understood selection processes. For some of the catalyst/substrate complexes, experimental proof points out the validation of the major/minor principle; the concentration-deficient minor substrate complex, which has very high reactivity, yields the excess enantiomer. As exemplified by the reaction system of [Rh(dipamp)(MeOH)2]+/methyl (Z)-alpha-acetamidocinnamate (dipamp=1,2-bis((o-methoxyphenyl)phenylphosphino)ethane), all six of the characteristic reaction rate constants have been previously identified. Recently, it was found that the major substrate complex can also yield the major enantiomer (lock-and-key principle). The differential equation system that results from the reaction sequence can be solved numerically for different hydrogen partial pressures by including the known equilibrium constants. The result displays the concentration-time dependence of all species that exist in the catalytic cycle. On the basis of the known constants as well as further experimental evidence, this work focuses on the examination of all principal possibilities resulting from the reaction sequence and leading to different results for the stereochemical outcome. From the simulation, the following conclusions can be drawn: 1) When an intermediate has extreme reactivity, its stationary concentration can become so small that it can no longer be the source of product selectivity; 2) in principle, the major/minor and lock-and-key principles can coexist depending on the applied pressure; 3) thermodynamically determined intermediate ratios can be completely converted under reaction conditions for a selection process; and 4) the increase in enantioselectivity with increasing hydrogen partial pressure, a phenomenon that is experimentally proven but theoretically far from being well-understood, can be explained by applying both the lock-and-key as well as the major

  18. Selective cesium and strontium removal for TRU-liquid waste including fission products and concentrated nitric acids

    International Nuclear Information System (INIS)

    Mimori, T.; Miyajima, K.; Kozeki, M.; Kubota, T.; Tusa, E.; Keskinen, A.

    1996-01-01

    A nuclide removal system was designed for treatment of liquid radioactive waste at the Japan Atomic Energy Research Institute (JAERI) Tokai site. Total system will include removal of plutonium, cesium and strontium. Removal of plutonium will be carried out by a method developed by JAERI. Removal of cesium and strontium will be carried out by the methods developed in Finland. The whole project will be implemented for JAERI in cooperation between Mitsui Engineering and Shipbuilding and IVO International. This project has been carried out under the Science and Technology Agency (STA) of Japan. The liquid to be treated includes 7.4x10 9 Bq/L of cesium and 7.4x10 9 Bq/L of strontium. The amount of alpha nuclides is 3.7x10 6 Bq/L. Nitric acid concentration is 1.74 mol/L. The volume of 11,000 liters had to be treated in 200 batches of operation. Removal of cesium and strontium is based on the use of new ion exchange materials developed in Finland. These inorganic ion exchange materials have extremely good properties to separate cesium and strontium from even very difficult liquids. Ion exchange material will be used in columns, where there are materials both for cesium and strontium. According to column tests with simulated waste, one 2 liter column will effectively reach the required DF during 10 batches of operation. Purified liquid can be led to further liquid treatment at the site. After treatment of liquids, both used particle filters and used ion exchange columns will be drained and stored to wait for final treatment and disposal. The designed treatment system has a special beneficial feature as it does not produce secondary waste. Final waste is in the form of particle filters or ion exchange columns with material. Used ion exchange columns and filters will be replaced with new ones by means of remote handling. Construction of the treatment system will be scheduled to commence in FY1995 and assemblying at the site in FY1996. (J.P.N.)

  19. A flow system for generation of concentration perturbation in two-dimensional correlation near-infrared spectroscopy: application to variable selection in multivariate calibration.

    Science.gov (United States)

    Pereira, Claudete Fernandes; Pasquini, Celio

    2010-05-01

    A flow system is proposed to produce a concentration perturbation in liquid samples, aiming at the generation of two-dimensional correlation near-infrared spectra. The system presents advantages in relation to batch systems employed for the same purpose: the experiments are accomplished in a closed system; application of perturbation is rapid and easy; and the experiments can be carried out with micro-scale volumes. The perturbation system has been evaluated in the investigation and selection of relevant variables for multivariate calibration models for the determination of quality parameters of gasoline, including ethanol content, MON (motor octane number), and RON (research octane number). The main advantage of this variable selection approach is the direct association between spectral features and chemical composition, allowing easy interpretation of the regression models.

  20. The concentration of heavy metals: zinc, cadmium, lead, copper, mercury, iron and calcium in head hair of a randomly selected sample of Kenyan people

    International Nuclear Information System (INIS)

    Wandiga, S.O.; Jumba, I.O.

    1982-01-01

    An intercomparative analysis of the concentration of heavy metals:zinc, cadmium, lead, copper, mercury, iron and calcium in head hair of a randomly selected sample of Kenyan people using the techniques of atomic absorption spectrophotometry (AAS) and differential pulse anodic stripping voltammetry (DPAS) has been undertaken. The percent relative standard deviation for each sample analysed using either of the techniques show good sensitivity and correlation between the techniques. The DPAS was found to be slightly sensitive than the AAs instrument used. The recalculated body burden rations of Cd to Zn, Pb to Fe reveal no unusual health impairement symptoms and suggest a relatively clean environment in Kenya.(author)

  1. Selective oxidation of glycerol to formic acid in highly concentrated aqueous solutions with molecular oxygen using V-substituted phosphomolybdic acids

    KAUST Repository

    Zhang, Jizhe

    2014-01-01

    Formic acid is an important commodity chemical as well as a promising medium for hydrogen storage and hydrogen production. In this paper, we report that formic acid can be produced through selective oxidation of glycerol, a low-cost by-product of biodiesel, by using vanadium-substituted phosphomolybdic acids as catalysts and molecular oxygen as the oxidant. Significantly, this catalytic system allows for high-concentration conversions and thus leads to exceptional efficiency. Specifically, 3.64 g of formic acid was produced from 10 g of glycerol/water (50/50 in weight) solution. © 2014 the Partner Organisations.

  2. Direct determination of Ti content in sunscreens with laser-induced breakdown spectroscopy: Line selection method for high TiO{sub 2} nanoparticle concentration

    Energy Technology Data Exchange (ETDEWEB)

    Menneveux, Jérôme; Wang, Fang; Lu, Shan; Bai, Xueshi; Motto-Ros, Vincent [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex (France); Gilon, Nicole [Institut des Sciences Analytiques, UMR5280 Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex (France); Chen, Yanping [Department of Physics and Astrophysics, Shanghai Jiao Tong University, Shanghai 200240 (China); Yu, Jin, E-mail: jin.yu@univ-lyon1.fr [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex (France); Department of Physics and Astrophysics, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2015-07-01

    Sunscreen represents a large variety of creams which, in the analytical point of view, exhibit a similar matrix. Such matrix corresponds to a semi-solid emulsion of mixture of oil and water. The formulation of a cream can include metal and nonmetal elements in different contents in order to realize specific pharmaceutical or cosmetic functions designed for the product. The complex matrix of these materials makes their analysis challenging for classical elemental analytical techniques with specific and complicated sample pretreatment procedures needed for reliable quantification. In this work we demonstrate and assess direct determination, without any pretreatment, of elemental content, especially for metallic element such as titanium, in a sunscreen using laser-induced breakdown spectroscopy (LIBS). The used configuration corresponds to that of indirect ablation of a thin film of cream applied on the surface of a pure aluminum target. We especially focused, in this work, on the case of high concentration of TiO{sub 2} nanoparticle in cream. Such choice was justified first by the fact that such concentration level is usually found in commercial sunscreens. On the other hand, titanium presents a large number of lines, neutral as well as singly ionized, in the spectral range from the near UV to the near IR. It provides therefore an ideal case to study line selection method to manage the effect of self-absorption, which becomes unavoidable at high concentration level, and to optimize measurement precision. Through such study, we try to deduce a quantifiable and generalizable line selection method for high performance LIBS measurements. More specifically, calibration curves were first established using 6 laboratory-prepared samples. The quadratic term of the curves was then studied as a function of the intensity of the used lines and their type (neutral or ion, resonant or non-resonant). The prediction performance of the lines was assessed with 2 validation samples with

  3. Pharmacological modification of multi-drug resistance (MDR) in vitro detected by a novel fluorometric microculture cytotoxicity assay. Reversal of resistance and selective cytotoxic actions of cyclosporin A and verapamil on MDR leukemia T-cells.

    Science.gov (United States)

    Larsson, R; Nygren, P

    1990-07-15

    A novel fluorometric microculture cytotoxicity assay (FMCA), based on measurements of fluorescein diacetate (FDA) hydrolysis and DNA staining by Hoechst 33342, was used for drug sensitivity testing and detection of resistance reversal in acute lymphoblastic leukemia (ALL) cell lines. The 72-hr assay was found to be sensitive, reproducible and linearly related to the number of viable cells within a broad range of cell concentrations. At clinically achievable drug concentrations, the calcium channel blocker Verapamil (ver) and the immunosuppressant Cyclosporin A (csA) were found to partly reverse acquired Vincristine (vcr) resistance in multi-drug resistant (MDR) T-ALL L100 cells with little or no effect on the drug-sensitive parental L0 cell line. By combining the fluorometric indices, we found that low concentrations of csA were growth-inhibitory, whereas higher concentrations (greater than 10 micrograms/ml) were progressively cytotoxic for drug-sensitive L0 cells. In MDR L100 cells, on the other hand, csA produced significant cell kill even at low drug concentrations. Ver had no effects on sensitive L0 cells but showed considerable cytotoxic action towards MDR L100 cells. There was no apparent relationship between drug reversal of vcr resistance and the cytotoxic actions of the drug per se since the calcium channel blocker diltiazem (dil) significantly potentiated the actions of vcr on MDR L100 cells without being more toxic to these cells (compared to vcr-sensitive L0 cells).

  4. Mercury concentrations in water and mercury and selenium concentrations in fish from Brownlee Reservoir and selected sites in the Boise and Snake Rivers, Idaho and Oregon, 2013–15

    Science.gov (United States)

    Williams, Marshall L.; MacCoy, Dorene E.

    2016-06-30

    Mercury (Hg) analyses were conducted on samples of sport fish and water collected from selected sampling sites in Brownlee Reservoir and the Boise and Snake Rivers to meet National Pollution Discharge and Elimination System (NPDES) permit requirements for the City of Boise, Idaho, between 2013 and 2015. City of Boise personnel collected water samples from six sites between October and November 2013 and 2015, with one site sampled in 2014. Total Hg concentrations in unfiltered water samples ranged from 0.48 to 8.8 nanograms per liter (ng/L), with the highest value in Brownlee Reservoir in 2013. All Hg concentrations in water samples were less than the U.S. Environmental Protection Agency (USEPA) Hg chronic aquatic life criterion of 12 ng/L.The USEPA recommended a water-quality criterion of 0.30 milligrams per kilogram (mg/kg) methylmercury (MeHg) expressed as a fish-tissue residue value (wet-weight MeHg in fish tissue). The Idaho Department of Environmental Quality adopted the USEPA’s fish-tissue criterion and established a reasonable potential to exceed (RPTE) threshold 20 percent lower than the criterion or greater than 0.24 mg/kg Hg based on an average concentration of 10 fish from a receiving waterbody. NPDES permitted discharge to waters with fish having Hg concentrations exceeding 0.24 mg/kg are said to have a reasonable potential to exceed the water-quality criterion and thus are subject to additional permit obligations, such as requirements for increased monitoring and the development of a Hg minimization plan. The Idaho Fish Consumption Advisory Program (IFCAP) issues fish advisories to protect general and sensitive populations of fish consumers and has developed an action level of 0.22 mg/kg Hg in fish tissue. Fish consumption advisories are water body- and species-specific and are used to advise allowable fish consumption from specific water bodies. The geometric mean Hg concentration of 10 fish of a single species collected from a single water body

  5. The role of tin-promoted Pd/MWNTs via the management of carbonaceous species in selective hydrogenation of high concentration acetylene

    International Nuclear Information System (INIS)

    Esmaeili, Elaheh; Mortazavi, Yadollah; Khodadadi, Abbas Ali; Rashidi, Ali Morad; Rashidzadeh, Mehdi

    2012-01-01

    Highlights: ► Synthesis of highly active tin-promoted catalysts by polyol method for selective hydrogenation of high concentration of acetylene. ► A positive change in the catalytic activities of tin-promoted catalysts results from distinct geometric and electronic effects. ► Change in the coverage of acetylenic overlayers for different temperature regions corresponds to the change of the number of isolated adsorption sites. ► The isolated adsorption sites are responsible for the enhancement of selectivity to ethylene with increased temperatures, via the management of the carbonaceous species over the catalyst surface. - Abstract: In the present study, Pd/MWNTs are synthesized using polyol process and modified by tin as a promoter for selective hydrogenation of high concentrated acetylene feedstock. Polyol method results in highly dispersed nanoparticles with a depletion of particle size for tin-promoted Pd catalysts as characterized by TEM. Tin promoter plays a considerable role in hydrogenation of pure acetylene stream. This is attributed to formation of Pd 2 Sn structural phase, confirmed by XRD and TPR techniques, composed mainly of intermetallic species. Catalytic behavior of tin-promoted Pd catalysts is affected by geometric and electronic factors which are more pronounced in the case of Sn/Pd = 0.25. A discontinuity in Arrhenius plots for the Sn-promoted catalysts is appeared, which seems to be due to a kinetic factor as a result of change in acetylene coverage on Pd metallic ensembles at low and high temperature ranges. Higher selectivity of the catalysts to ethylene is attributed to the presence of more isolated adsorption sites on the catalyst surface originated from both intermetallic compounds confirmed by XPS and the ones formed via the carbonaceous species upon the acetylene hydrogenation reaction.

  6. Pharmacological challenges in chronic pancreatitis

    OpenAIRE

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal ...

  7. Pharmacological treatment of sexual offenders in German outpatient treatment centers.

    Science.gov (United States)

    Turner, Daniel; Gregório Hertz, Priscilla; Sauter, Julia; Briken, Peer; Rettenberger, Martin

    2018-05-04

    In Germany, depending on a sexual offender's culpability and the severity of the offence, he/she can be placed either in the forensic-psychiatric or the correctional system. Numbers related to the pharmacological treatment of sexual offenders for the correctional system are missing so far. In sexual offenders, the pharmacological treatment of paraphilic disorders is of special importance. The present study aimed at assessing the prevalence of pharmacological sexual offender treatment in German outpatient treatment centers supervising mainly clients from the correctional sector. An online questionnaire was sent to 112 outpatient treatment centers and 21 provided data relevant for the present study. The included institutions reported about a total of 813 sexual offenders, of whom 200 (24.6%) were treated with pharmacological agents, most frequently antipsychotics (14.8%) and selective-serotonin-reuptake-inhibitors (7.1%). Of the total sample, 26.7% of sexual offenders were diagnosed with a paraphilic - mainly with a pedophilic - disorder. Only 2% were treated with androgen-deprivation therapy. Compared with forensic-psychiatric institutions, only a minority of sexual offenders are treated with medication specifically addressing paraphilic symptomatology. However, the prevalence of paraphilic disorders found in the present study suggests that pharmacological treatment of paraphilic fantasies and behaviors could be of great importance in the correctional sector as well.

  8. A Review of Pharmacologic Treatment for Compulsive Buying Disorder.

    Science.gov (United States)

    Soares, Célia; Fernandes, Natália; Morgado, Pedro

    2016-04-01

    At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.

  9. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  10. Particle size distributions, size concentration relationships, and adherence to hands of selected geologic media derived from mining, smelting, and quarrying activities

    Energy Technology Data Exchange (ETDEWEB)

    Bergstrom, Carolyn; Shirai, Jeffry; Kissel, John, E-mail: jkissel@uw.edu

    2011-09-15

    Hand-to-mouth activity, especially in children, is a potentially significant pathway of exposure to soil contaminants. Hand-mouthing behavior is of particular concern in areas impacted by mining, smelting, and quarrying activities as these activities may lead to elevated levels of heavy metals in soil. In order to estimate potential exposures to contaminated geologic media attributable to hand-to-mouth contact, it is useful to characterize adherence of those media to skin, as contaminant concentrations in adhered media may differ greatly from unfractionated, whole media concentrations. Such an investigation has been undertaken to aid estimation of exposures to arsenic, cadmium, lead, and zinc in nine different geologic media collected in the Pacific Northwest region of the United States. After establishing the particle size distribution of each medium (fractions < 63 {mu}m, 63-150 {mu}m, 150-250 {mu}m, and 250 {mu}m-2 mm were determined) and target elemental concentrations within each particle size fraction, an active handling protocol involving six volunteers was conducted. Wet media always adhered to a greater extent than dry media and adhered media generally had higher elemental concentrations than bulk media. Regression analyses suggest smaller particle fractions may have higher elemental concentrations. Results of application of a maximum likelihood estimation technique generally indicate that handling of dry media leads to preferential adherence of smaller particle sizes, while handling of wet media does not. Because adhered material can differ greatly in particle size distribution from that found in bulk material, use of bulk concentrations in exposure calculations may lead to poor estimation of actual exposures. Since lead has historically been a metal of particular concern, EPA's Integrated Exposure Uptake Biokinetic (IEUBK) Model was used to examine the potential consequences of evaluating ingestion of the selected media assuming concentrations in

  11. Plasma concentration of selected biochemical markers of endothelial dysfunction in women with various severity of chronic venous insufficiency (CVI-A pilot study.

    Directory of Open Access Journals (Sweden)

    Magdalena Budzyń

    Full Text Available Although the endothelial dysfunction is considered to be implicated in the pathogenesis of chronic venous insufficiency (CVI the endothelial status in patients with venous disorders is still not fully evaluated. Therefore the aim of the study was to measure the concentration of selected markers of endothelial dysfunction: von Willebrand factor (vWf, soluble P-selectin (sP-selectin, soluble thrombomodulin (sTM and soluble VE-cadherin (sVE-cadherin in CVI women who constitute the most numerous group of patients suffering from venous disease.Forty four women with CVI were involved in the study and divided into subgroups based on CEAP classification. Concentration of vWf, sP-selectin, sTM and sVE-cadherin were measured and compared with those obtained in 25 healthy age and sex-matched women.It was found that the concentration of sTM increased and sVEcadherin decreased along with disease severity in CVI women. A significant rise of sTM was observed especially in CVI women, with the highest inflammation status reflected by hsCRP or elastase concentration, and in CVI women with a high oxidative stress manifested by an increased plasma MDA. A significant fall of circulating sVE-cadherin was reported in CVI women with moderate to highest intensity of inflammation and oxidative stress. There was no change in vWF and sP-selectin concentration at any stage of CVI severity.The results of the present study demonstrate the presence of endothelial dysfunction in women suffering from CVI which seems to progress with the disease severity and may be associated with inflammation and enhanced oxidative stress.

  12. Selective kainate receptor (GluK1) ligands structurally based upon1H-Cyclopentapyrimidin-2,4(1H,3H)-dione: synthesis, molecular modeling, and pharmacological and biostructural characterization

    DEFF Research Database (Denmark)

    Venskutonyte, Raminta; Butini, Stefania; Coccone, Salvatore Sanna

    2011-01-01

    The physiological function of kainate receptors (GluK1- GluK5) in the central nervous system is not fully understood yet. With the aim of developing potent and selective GluK1 ligands, we have synthesized a series of new thiophene-based GluK1 agonists (6a-c) and antagonists (7a-d). Pharmacologica...

  13. Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)

    DEFF Research Database (Denmark)

    Bjerrum, Esben J; Kristensen, Anders S; Pickering, Darryl S

    2003-01-01

    On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. ...

  14. Selection of suitable mineral acid and its concentration for biphasic dilute acid hydrolysis of the sodium dithionite delignified Prosopis juliflora to hydrolyze maximum holocellulose.

    Science.gov (United States)

    Naseeruddin, Shaik; Desai, Suseelendra; Venkateswar Rao, L

    2016-02-01

    Two grams of delignified substrate at 10% (w/v) level was subjected to biphasic dilute acid hydrolysis using phosphoric acid, hydrochloric acid and sulfuric acid separately at 110 °C for 10 min in phase-I and 121 °C for 15 min in phase-II. Combinations of acid concentrations in two phases were varied for maximum holocellulose hydrolysis with release of fewer inhibitors, to select the suitable acid and its concentration. Among three acids, sulfuric acid in combination of 1 & 2% (v/v) hydrolyzed maximum holocellulose of 25.44±0.44% releasing 0.51±0.02 g/L of phenolics and 0.12±0.002 g/L of furans, respectively. Further, hydrolysis of delignified substrate using selected acid by varying reaction time and temperature hydrolyzed 55.58±1.78% of holocellulose releasing 2.11±0.07 g/L and 1.37±0.03 g/L of phenolics and furans, respectively at conditions of 110 °C for 45 min in phase-I & 121 °C for 60 min in phase-II. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Pharmacological chaperoning: a primer on mechanism and pharmacology.

    Science.gov (United States)

    Leidenheimer, Nancy J; Ryder, Katelyn G

    2014-05-01

    Approximately forty percent of diseases are attributable to protein misfolding, including those for which genetic mutation produces misfolding mutants. Intriguingly, many of these mutants are not terminally misfolded since native-like folding, and subsequent trafficking to functional locations, can be induced by target-specific, small molecules variably termed pharmacological chaperones, pharmacoperones, or pharmacochaperones (PCs). PC targets include enzymes, receptors, transporters, and ion channels, revealing the breadth of proteins that can be engaged by ligand-assisted folding. The purpose of this review is to provide an integrated primer of the diverse mechanisms and pharmacology of PCs. In this regard, we examine the structural mechanisms that underlie PC rescue of misfolding mutants, including the ability of PCs to act as surrogates for defective intramolecular interactions and, at the intermolecular level, overcome oligomerization deficiencies and dominant negative effects, as well as influence the subunit stoichiometry of heteropentameric receptors. Not surprisingly, PC-mediated structural correction of misfolding mutants normalizes interactions with molecular chaperones that participate in protein quality control and forward-trafficking. A variety of small molecules have proven to be efficacious PCs and the advantages and disadvantages of employing orthostatic antagonists, active-site inhibitors, orthostatic agonists, and allosteric modulator PCs are considered. Also examined is the possibility that several therapeutic agents may have unrecognized activity as PCs, and this chaperoning activity may mediate/contribute to therapeutic action and/or account for adverse effects. Lastly, we explore evidence that pharmacological chaperoning exploits intrinsic ligand-assisted folding mechanisms. Given the widespread applicability of PC rescue of mutants associated with protein folding disorders, both in vitro and in vivo, the therapeutic potential of PCs is vast

  16. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting.

    Science.gov (United States)

    Bridgeman, Mary Barna; Abazia, Daniel T

    2017-03-01

    The authors review the historical use of medicinal cannabis and discuss the agent's pharmacology and pharmacokinetics, select evidence on medicinal uses, and the implications of evolving regulations on the acute care hospital setting.

  17. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting

    OpenAIRE

    Bridgeman, Mary Barna; Abazia, Daniel T.

    2017-01-01

    The authors review the historical use of medicinal cannabis and discuss the agent?s pharmacology and pharmacokinetics, select evidence on medicinal uses, and the implications of evolving regulations on the acute care hospital setting.

  18. Accounting for Genotype-by-Environment Interactions and Residual Genetic Variation in Genomic Selection for Water-Soluble Carbohydrate Concentration in Wheat.

    Science.gov (United States)

    Ovenden, Ben; Milgate, Andrew; Wade, Len J; Rebetzke, Greg J; Holland, James B

    2018-05-31

    Abiotic stress tolerance traits are often complex and recalcitrant targets for conventional breeding improvement in many crop species. This study evaluated the potential of genomic selection to predict water-soluble carbohydrate concentration (WSCC), an important drought tolerance trait, in wheat under field conditions. A panel of 358 varieties and breeding lines constrained for maturity was evaluated under rainfed and irrigated treatments across two locations and two years. Whole-genome marker profiles and factor analytic mixed models were used to generate genomic estimated breeding values (GEBVs) for specific environments and environment groups. Additive genetic variance was smaller than residual genetic variance for WSCC, such that genotypic values were dominated by residual genetic effects rather than additive breeding values. As a result, GEBVs were not accurate predictors of genotypic values of the extant lines, but GEBVs should be reliable selection criteria to choose parents for intermating to produce new populations. The accuracy of GEBVs for untested lines was sufficient to increase predicted genetic gain from genomic selection per unit time compared to phenotypic selection if the breeding cycle is reduced by half by the use of GEBVs in off-season generations. Further, genomic prediction accuracy depended on having phenotypic data from environments with strong correlations with target production environments to build prediction models. By combining high-density marker genotypes, stress-managed field evaluations, and mixed models that model simultaneously covariances among genotypes and covariances of complex trait performance between pairs of environments, we were able to train models with good accuracy to facilitate genetic gain from genomic selection. Copyright © 2018 Ovenden et al.

  19. Revealing mechanisms of selective, concentration-dependent potentials of 4-hydroxy-2-nonenal to induce apoptosis in cancer cells through inactivation of membrane-associated catalase.

    Science.gov (United States)

    Bauer, Georg; Zarkovic, Neven

    2015-04-01

    Tumor cells generate extracellular superoxide anions and are protected against superoxide anion-mediated intercellular apoptosis-inducing signaling by the expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a versatile second messenger generated during lipid peroxidation, has been shown to induce apoptosis selectively in malignant cells. The findings described in this paper reveal the strong, concentration-dependent potential of 4-HNE to specifically inactivate extracellular catalase of tumor cells both indirectly and directly and to consequently trigger apoptosis in malignant cells through superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4-HNE caused apoptosis selectively in NOX1-expressing tumor cells through inactivation of their membrane-associated catalase, thus reactivating subsequent intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 µM and higher directly inactivated membrane-associated catalase of tumor cells, whereas at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on initial singlet oxygen formation through H2O2 and peroxynitrite interaction. Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased superoxide anion generation by NOX1 and amplification of singlet oxygen generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4-HNE and singlet oxygen cooperate in complex autoamplificatory loops during this process. The finding of these novel anticancer pathways may be useful for understanding the role of 4-HNE in the control of malignant cells and for the optimization of ROS-dependent therapeutic approaches including antioxidant treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Serum concentrations of lipids, vitamin d metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos.

    Science.gov (United States)

    Crissey, Susan D; Ange, Kimberly D; Jacobsen, Krista L; Slifka, Kerri A; Bowen, Phyllis E; Stacewicz-Sapuntzakis, Maria; Langman, Craig B; Sadler, William; Kahn, Stephen; Ward, Ann

    2003-01-01

    Serum concentrations of several nutrients were measured in 12 captive wild felid species including caracal (Felis caracal), cheetah (Acinonyx jubatus), cougar (Felis concolor), fishing cat (Felis viverrinus), leopard (Panthera pardus), lion (Panthera leo), ocelot (Felis pardalis), pallas cat (Felis manul), sand cat (Felis margarita), serval (Felis serval), snow leopard (Panthera uncia) and tiger (Panthera tigris). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens and North Carolina Zoological Park). The nutritional composition of the diets at each institution met the probable dietary requirements for each species except for the pallas cat. Blood samples were collected from each animal (n = 69) and analyzed for lipids (total cholesterol, triacylglycerides, HDL cholesterol and LDL cholesterol), vitamin D metabolites [25-hydroxycholecalciferol (25(OH)D) and 1,25-dihydroxycholecalciferol (1,25(OH)(2)D)], vitamin A (retinol, retinyl stearate and retinyl palmitate), vitamin E (alpha- and gamma-tocopherol) and selected carotenoids. Species differences were found for all except triacylglycerides and 1,25(OH)(2)D. Genus differences were found for retinol, retinyl palmitate, retinyl stearate, gamma-tocopherol and beta-carotene. Circulating nutrient concentrations for many of the species in this study have not been reported previously and most have not been compared with the animals' dietary intakes. The large number of animals analyzed provides a substantial base for comparing the serum nutrient concentrations of healthy animals, for both wild and captive exotic species.

  1. Concentrations of Selected Metals In Some Ready-To-Eat-Foods Consumed in Southern Nigeria: Estimation of Dietary Intakes and Target Hazard Quotients

    Directory of Open Access Journals (Sweden)

    Chukwujindu Maxwell Iwegbue

    2013-12-01

    Full Text Available Concentrations of selected metals (Cu, Cd, Ni, Pb, Mn, Fe, Zn, Cr and Co in some ready-to-eat-foods consumed in Nigeria were investigated with a view providing information on the risk associated with the consumption of these products. The concentrations of metals (mg.kg-1 in these ready-to-eat-foods are in the ranges of 2.4 – 5.2 for Cu; 0.1– 0.8 for Cd; 0.7 – 4.0 for Ni; 8.1 – 53.7 for Fe; 8.9 – 20.0 for Zn; 0.1 – 3.8 for Pb; 5.1 – 14.4 for Mn; 0.83 – 21.4 for Cr and 0.20 – 1.32 for Co. The concentrations and estimated intakes of Cd, Ni and Pb in some of these food types exceeded the permissible limits and tolerable daily intake respectively. The target hazard quotients (THQ for the individual metals indicate levels of concern for Ni, Cd, and Co in some of the ready-to-eat-foods. The combined THQ values for the metals in the examined samples ranged from 1.7 to 10 with significant contributions from Cd, Ni and Co.

  2. Determination of minumun inhibitory concentration (MIC of Hygromycin B and it’s use like selective agent in Mycosphaerella fijiensis transformation

    Directory of Open Access Journals (Sweden)

    Mileidy Cruz-Martín

    2001-04-01

    Full Text Available The Black sigatoka can be considered from the economic point of view the most serious disease in the gender Musa. At present the use of new biotechnological techniques applied to the study of the host-pathogen interation is glimpsed as an important tool in the future improvement of the commercial cultivars of the banana and plantain. In this study, we tested diferents concentration of Hygromycin B against an isolate of M. fijiensis (CCIBP-1 by the agar dilution method. It was proved that Hygromycin B was able to inhibit the growth of the M. fijiensis starting from 0.5 mg.l-1. This value was taken as the minimum inhibitory concentration, that’s why it could be used like selective agent in the transformation studies of Mycosphaerella complex. By another hands it was demostrated the value of the previous protocol of the Minimum Inhibitory concentration for making evaluations of different fungus pathogens against antimicribial substance. Key words: antibiotic, Black sigatoka, phytopathogen

  3. Compilation of selected marine radioecological data for the US Subseabed Program: Summaries of available radioecological concentration factors and biological half-lives

    International Nuclear Information System (INIS)

    Gomez, L.S.; Marietta, M.G.; Jackson, D.W.

    1987-04-01

    The US Subseabed Disposal Program has compiled an extensive concentration factor and biological half-life data base from the international marine radioecological literature. A microcomputer-based data management system has been implemented to provide statistical and graphic summaries of these data. The data base is constructed in a manner which allows subsets to be sorted using a number of interstudy variables such as organism category, tissue/organ category, geographic location (for in situ studies), and several laboratory-related conditions (e.g., exposure time and exposure concentration). This report updates earlier reviews and provides summaries of the tabulated data. In addition to the concentration factor/biological half-life data base, we provide an outline of other published marine radioecological works. Our goal is to present these data in a form that enables those concerned with predictive assessment of radiation dose in the marine environment to make a more judicious selection of data for a given application. 555 refs., 19 figs., 7 tabs

  4. Compilation of selected marine radioecological data for the US Subseabed Program: Summaries of available radioecological concentration factors and biological half-lives

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, L.S.; Marietta, M.G.; Jackson, D.W.

    1987-04-01

    The US Subseabed Disposal Program has compiled an extensive concentration factor and biological half-life data base from the international marine radioecological literature. A microcomputer-based data management system has been implemented to provide statistical and graphic summaries of these data. The data base is constructed in a manner which allows subsets to be sorted using a number of interstudy variables such as organism category, tissue/organ category, geographic location (for in situ studies), and several laboratory-related conditions (e.g., exposure time and exposure concentration). This report updates earlier reviews and provides summaries of the tabulated data. In addition to the concentration factor/biological half-life data base, we provide an outline of other published marine radioecological works. Our goal is to present these data in a form that enables those concerned with predictive assessment of radiation dose in the marine environment to make a more judicious selection of data for a given application. 555 refs., 19 figs., 7 tabs.

  5. Iomazenil: pharmacological and animal data

    International Nuclear Information System (INIS)

    Beer, H.F.; Blaeuenstein, P.A.; Hasler, P.H.; Schubiger, P.A.; Hunkeler, W.; Bibettu, E.P.; Pieri, L.; Grayson Richards, J.

    1990-01-01

    The flumazenil analogue Ro 16-0154 (Iomazenil), a benzodiazepine partial inverse agonist, has been labelled by halogen exchange to enable SPECT investigations of central benzodiazepine receptors in human brain. The purified 123 I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations. Its pharmacological properties were comparable to those of flumazenil with the exception of the antagonism of diazepam versus pentylenetetrazol. Biodistribution in rats (1 h p.i.) resulted in a high brain to blood ratio of 16. Clinical studies revealed images of the bezodiazepine receptor density in the brain. (author) 9 figs., 3 tabs., 27 refs

  6. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  7. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich-Christian; Semb, Synne; Nojgaard, Camilla

    2008-01-01

    -steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies...... pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted....... against tumor necrosis factor-alpha (TNF-alpha) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based...

  8. Gaultheria: Phytochemical and Pharmacological Characteristics

    Directory of Open Access Journals (Sweden)

    Ren-Bing Shi

    2013-09-01

    Full Text Available The genus Gaultheria, comprised of approximately 134 species, is mostly used in ethnic drugs to cure rheumatism and relieve pain. Phytochemical investigations of the genus Gaultheria have revealed the presence of methyl salicylate derivatives, C6-C3 constituents, organic acids, terpenoids, steroids, and other compounds. Methyl salicylate glycoside is considered as a characteristic ingredient in this genus, whose anti-rheumatic effects may have a new mechanism of action. In this review, comprehensive information on the phytochemistry, volatile components and the pharmacology of the genus Gaultheria is provided to explore its potential and advance research.

  9. Covalent co-immobilization of heparin/laminin complex that with different concentration ratio on titanium surface for selectively direction of platelets and vascular cells behavior

    International Nuclear Information System (INIS)

    Wang, Jian; Chen, Yuan; Liu, Tao; Wang, Xue; Liu, Yang; Wang, Yuan; Chen, Junying; Huang, Nan

    2014-01-01

    Highlights: • Extracellular matrix inspired surface modification with fibronectin, heparin and VEGF to construct a favorable microenvironment for selectively anticoagulant and promote endothelialization. • Take the advantage of specific intermolecular interaction, the bioactivity of above biomolecules was more efficiently maintained in compared with the common used covalent immobilization method. • Poly-l-lysine was used as a novel interlayer for surface amination, and in comparison, PLL coating was more feasible and the degradation product had no harm to human body. - Abstract: Surface biofunctional modification of coronary artery stent to improve the hemocompatibility and selectively accelerate endothelium regeneration but prevent restenosis have been become a new hotspot. For this, a novel method was developed in this work by co-immobilization of Ln and heparin complex on poly-L-lysine modified Ti surface. Take the advantage of the specific interaction between Ln and heparin, Ln and heparin complexes with different concentration ratios were set up for creating different exposure density of these two types of biomolecules. According to biocompatibility evaluation results, the Hep/Ln complexes modified surface displayed less platelet adhesion and activation. Especially, on L(150)H and L(200)H surface, the AT III binding quantity, APTT value and anti-coagulation property of modified surface were significantly promoted. Furthermore, the adherent density and proliferation activity of ECs and EPCs were positively correlated with Ln concentration. Notably, the proliferation of both ECs and EPCs on L(100)H, L(150)H and L(200)H surface were greatly promoted. Another hand, the proliferation activity of SMCs was significantly inhibited on Hep/Ln modified surfaces, which was considered mainly due to the inhibitory effect of heparin to SMCs. According to the existing results, this study demonstrated that in a certain range of heparin and laminin concentration ratio

  10. The effects of pH and concentration on heavy metal speciation and mobility, and its relation to heavy metal hyperaccumulation and distribution in selected native Australian flora

    International Nuclear Information System (INIS)

    Menon, D.D.; McPhail, D.C.; Hallam, N.

    2000-01-01

    Full text: The purpose of this research is to establish a clearer understanding of the relations that exist between heavy metal activity, speciation, bioavailability and their uptake and spatial distribution into plants. A combination of experimental modeling and pot trials using toxic heavy metals (cadmium, lead, mercury, copper, chromium and zinc) will be carried out. In the experiments, selected native Australian flora (Eucalyptus, Acacia, Atriplex) adapted to adverse environmental conditions will be used. Varying external factors such as pH, and metal concentration altered the composition of heavy metal speciation in the soil solution. Mathematical and geochemical (PHREEQC) models were used to vary these factors and emulate the conditions under which experimentation will be taking place. These variations help determine the possible heavy metal speciation that would occur in both soil and hydroponic based experiments under given conditions. The rhizosphere, soil solution and the plant material will be analysed by Inductively Coupled Plasma Mass Spectroscopy (ICPMS). Proton Ion X-ray Emission (PIXE) and Secondary Ion Mass spectrometry will help ascertain the distribution, concentration of heavy metal taken up into plant tissues. Information derived from these data will be used to determine and understand how varying such environmental conditions and hence heavy metal speciation affect their bioavailability in the medium, and how their acceptance, accumulation and storage within the selected flora. Preliminary experimentation showed that, for lead and cadmium, the variation in soil solution pH affected the quantity of heavy metal accumulated into selected native Australian flora. ICP-MS analysis of plants subjected to a known soil solution spiked with 200 μmol of lead and cadmium showed that the quantities of lead and cadmium accumulated into plant sections (roots, stems and leaves) varied in the selected woody species. A. heteroclita, A. saligna, and A

  11. Selective agonists at group II metabotropic glutamate receptors: synthesis, stereochemistry, and molecular pharmacology of (S)- and (R)-2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid

    DEFF Research Database (Denmark)

    Clausen, Rasmus P; Bräuner-Osborne, Hans; Greenwood, Jeremy R

    2002-01-01

    Homologation of analogues of the central excitatory neurotransmitter glutamic acid (Glu), in which the distal carboxy group has been bioisosterically replaced by acidic heterocyclic units, has previously provided subtype selective ligands for metabotropic Glu receptors (mGluRs). The (S......)-form of the 1,2,5-thiadiazol-3-ol Glu analogue, 2-amino-3-(4-hydroxy[1,2,5]thiadiazol-3-yl)propionic acid (TDPA, 6), is an 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, which in addition stereospecifically activates group I mGluRs. We have now synthesized the (S)- and (R......)-forms of 2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid (homo-TDPA, 7) and shown that whereas neither enantiomer interacts with AMPA receptors, (S)- and (R)-7 appear to be selective and equipotent agonists at group II mGluRs as represented by the mGluR2 subtype. The activities of (S)- and (R)-7...

  12. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  13. Pharmacological management of panic disorder

    Directory of Open Access Journals (Sweden)

    Carlo Marchesi

    2008-03-01

    Full Text Available Carlo MarchesiPsychiatric Section, Department of Neuroscience, University of Parma, Parma, ItalyAbstract: Panic disorder (PD is a disabling condition which appears in late adolescence or early adulthood and affects more frequently women than men. PD is frequently characterized by recurrences and sometimes by a chronic course and, therefore, most patients require longterm treatments to achieve remission, to prevent relapse and to reduce the risks associated with comorbidity. Pharmacotherapy is one of the most effective treatments of PD. In this paper, the pharmacological management of PD is reviewed. Many questions about this effective treatment need to be answered by the clinician and discussed with the patients to improve her/his collaboration to the treatment plan: which is the drug of choice; when does the drug become active; which is the effective dose; how to manage the side effects; how to manage nonresponse; and how long does the treatment last. Moreover, the clinical use of medication in women during pregnancy and breastfeeding or in children and adolescents was reviewed and its risk-benefit balance discussed.Keywords: panic disorder, pharmacological treatment, treatment guidelines

  14. Clinical pharmacology of atovaquone and proguanil hydrochloride.

    Science.gov (United States)

    Beerahee, M

    1999-05-01

    Atovaquone and proguanil hydrochloride is a new antimalarial combination that is used for treatment and prophylaxis of malaria. The clinical pharmacology of atovaquone and proguanil was reviewed. Atovaquone is a highly lipophilic compound with low aqueous solubility, the absorption of which is limited by the rate and extent of dissolution. Dietary fat increases the rate and extent of atovaquone absorption, increasing AUC two- to threefold and C(max) fivefold over fasting. Proguanil is rapidly and extensively absorbed regardless of food intake. Atovaquone is highly protein bound (> 99%) but does not displace other highly protein bound drugs in vitro, indicating significant drug interactions arising from displacement are unlikely. Atovaquone is predominantly eliminated unchanged in feces, with negligible excretion in urine. Proguanil is partially metabolized and partially excreted unchanged in urine. Its principal metabolite, cycloguanil, is also excreted in urine. Metabolism of proguanil is mediated in the liver by the cytochrome P450 3A and 2C subfamilies. The elimination half-life of atovaquone is 2 to 3 days in adults and 1 to 2 days in children. The elimination half-lives of proguanil and cycloguanil are 12 to 15 hours in adults and children. Dosage adjustments based on body weight categories in children (1/4 dose for 11-20 kg, 1/2 dose for > 20-30 kg, 3/4 dose for > 30-40 kg, and full dose for > 40 kg) achieve plasma concentrations that are safe and effective during prophylaxis and treatment of malaria. No dose adjustments for race, proguanil metabolizer status, gender, or elderly patients are needed, or for patients with mild to moderately impaired renal or hepatic function. The clinical pharmacology of atovaquone and proguanil provides a rationale for the dosing regimens recommended for treatment and prophylaxis of malaria.

  15. Determination of Low Concentrations of Acetochlor in Water by Automated Solid-Phase Extraction and Gas Chromatography with Mass-Selective Detection

    Science.gov (United States)

    Lindley, C.E.; Stewart, J.T.; Sandstrom, M.W.

    1996-01-01

    A sensitive and reliable gas chromatographic/mass spectrometric (GC/MS) method for determining acetochlor in environmental water samples was developed. The method involves automated extraction of the herbicide from a filtered 1 L water sample through a C18 solid-phase extraction column, elution from the column with hexane-isopropyl alcohol (3 + 1), and concentration of the extract with nitrogen gas. The herbicide is quantitated by capillary/column GC/MS with selected-ion monitoring of 3 characteristic ions. The single-operator method detection limit for reagent water samples is 0.0015 ??g/L. Mean recoveries ranged from about 92 to 115% for 3 water matrixes fortified at 0.05 and 0.5 ??g/L. Average single-operator precision, over the course of 1 week, was better than 5%.

  16. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

    Science.gov (United States)

    Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J

    2016-01-01

    The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

  17. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

    Directory of Open Access Journals (Sweden)

    Pirow Bekker

    Full Text Available The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan, an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

  18. Pharmacological interactions of anti-inflammatory-analgesics in odontology.

    Science.gov (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-02-01

    In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments prescribed daily in odontology for moderate pain treatment and inflammation in the oral cavity. Paracetamol can interact with warfarin and therefore care should be taken with chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently are capable of reducing the efficacy of medicaments used for treating arterial hypertension, which act via a renal mechanism. Especial attention should be taken considering the risk of interaction between the antagonists of AT1 receptors of angiostensin II (ARAII) and the NSAIs.

  19. Preparative treatment with NaOH to selectively concentrate iron oxides of a Chilean volcanic soil material to produce effective heterogeneous Fenton catalyst

    International Nuclear Information System (INIS)

    Manzo, Valentina; Pizarro, Carmen; Rubio, María Angélica; Cavalcante, Luis Carlos Duarte; Garg, Vijayendra Kumar; Fabris, José Domingos

    2011-01-01

    A Chilean volcanic Ultisol material was first size-fractionated so as to obtain the fraction with mean particle sizes φ   − 1 NaOH, in an attempt to evaluate the effectiveness of the selective chemical dissolution to concentrate iron oxides, as a preparation procedure before using the materials as heterogeneous Fenton catalysts. The effects of those treatments on the iron oxides mineralogy were monitored with Mössbauer spectroscopy. The NaOH-treated samples were tested as catalysts towards the H 2 O 2 decomposition. Three or five sequential NaOH treatments were found to be comparably effective, by concentrating nearly the same proportion of iron oxides in the remaining solid phase (25.1 ± 0.4 and 23.3 ± 0.2 mass%, respectively). 298 K-Mössbauer patterns were similar for both samples, with a central (super)paramagnetic Fe 3 +  doublet and a broad sextet, assignable to several closely coexisting magnetically ordered forms of iron oxides. Despite of this nearly similar effect of the two treatments, the Ultisol material treated three times with NaOH presents higher heterogeneous catalytic efficiency and is more suitable to decompose H 2 O 2 than that with five treatments.

  20. Expression of selected pathway-marker genes in human urothelial cells exposed chronically to a non-cytotoxic concentration of monomethylarsonous acid

    Directory of Open Access Journals (Sweden)

    Matthew Medeiros

    2014-01-01

    Full Text Available Bladder cancer has been associated with chronic arsenic exposure. Monomethylarsonous acid [MMA(III] is a metabolite of inorganic arsenic and has been shown to transform an immortalized urothelial cell line (UROtsa at concentrations 20-fold less than arsenite. MMA(III was used as a model arsenical to examine the mechanisms of arsenical-induced transformation of urothelium. A previous microarray analysis revealed only minor changes in gene expression at 1 and 2 months of chronic exposure to MMA(III, contrasting with substantial changes observed at 3 months of exposure. To address the lack of information between 2 and 3 months of exposure (the critical period of transformation, the expression of select pathway marker genes was measured by PCR array analysis on a weekly basis. Cell proliferation rate, anchorage-independent growth, and tumorigenicity in SCID mice were also assessed to determine the early, persistent phenotypic changes and their association with the changes in expression of these selected marker genes. A very similar pattern of alterations in these genes was observed when compared to the microarray results, and suggested that early perturbations in cell signaling cascades, immunological pathways, cytokine expression, and MAPK pathway are particularly important in driving malignant transformation. These results showed a strong association between the acquired phenotypic changes that occurred as early as 1–2 months of chronic MMA(III exposure, and the observed gene expression pattern that is indicative of the earliest stages in carcinogenesis.

  1. Selective decontamination of cesium and strontium from evaporation concentrates of spent fuel reprocessing plants with crown ethers by transport through supported liquid membranes

    International Nuclear Information System (INIS)

    Casas i Garcia, J.

    1993-01-01

    Reprocessing operations lead to the production of radioactive medium activity liquid waste which is treated by evaporation and solutions of very high salinity are thus formed. The concentrates from reprocessing plant evaporators have to be stored in geological storage sites in view of their strong caesium, strontium and actinides activity. These elements, contained in acid and high sodium nitrate content liquid waste, are removed by means of selective extractants, using the supported liquid membrane technique (SLM), which allows them to be stored in surface sites, the actinides and long-life fission products being respectively recycled and concentrated into reduced volumes. The removal of the actinides is done by means of an Octyl N.N Diisobutyl Carbamoyl Methyl Phosphine Oxide (C.M.P.O.) based liquid membrane, whereas the removal of the caesium and strontium involves crown ethers. Supported liquid membranes (S.L.M.s) have the advantage of implementing very small quantities of extractant, but they generally have poor stability. The extractant, the diluent and the phase modifier impregnating the membrane play a vital role in SLM stability; the support also affects stability by its nature and geometry. For the extraction of strontium, the most lipophilic extractant, DtBu 18 C 6, enables higher strontium transfer kinetics to be attained. As regards caesium, the extremely lipophilic nDec B21 C7 is the most efficient. Caesium cannot be quantitatively removed, due to the competition of the very high content of sodium ions in the concentrate. Stable membranes are obtained with DC18 C6 or DtBu18 C6 diluted in alkylbenzenes with an added phase modifier such as decanol or especially isotridecanol

  2. Selective decontamination for cesium and strontium in evaporation concentrates from reprocessing plants with crown ethers by transport through supported liquid membranes

    International Nuclear Information System (INIS)

    Casas i Garcia, J.

    1991-01-01

    Reprocessing operations lead to the production of radioactive medium activity liquid waste which is treated by evaporation. The concentrates from reprocessing plant evaporators have to be stored in geological storage sites in view of their strong caesium, strontium and actinides activity. These elements, contained in acid and high sodium nitrate content liquid waste, are removed by means of selective extractants, using the supported liquid membrane technique (SLM), which allows them to be stored in surface sites, the actinides and long-life fission products being respectively recycled and concentrated into reduced volumes. The removal of the actinides is done by means of an Octyl N.N Diisobutyl Carbamoyl Methyl Phosphine Oxyde (C.M.P.O.) based liquid membrane, whereas the removal of the caesium and strontium involves crown ethers. Supported liquid membranes (S.L.M.s) have the advantage of implementing very small quantities of extractant, but, they generally have poor stability. The extractant, the diluent and the phase modifier that constitute the organic phase impregnating the membrane play a vital role in SLM stability; the support also affects stability by its nature and geometry. For the extraction of strontium, DtBu 18 C6 enables higher strontium transfer kinetics to be attained than with DC18 C6. As regards caesium, nDec B21 C7 is the most efficient. Unlike strontium, caesium cannot be quantitatively removed, due to the competition of sodium ions in the concentrate. Stable membranes are obtained with DC18 C6 or DtBu18 C6 diluted in alkylbenzene with an added phase modifier such as decanol or isotridecanol. The highest strontium transfer kinetics were obtained with the DC18 C6/hexylbenzene/isotridecanol mixture

  3. Pharmacology, pharmacokinetics and metabolism of the dopamine receptor agonist 5-hydroxy-6-methyl-2-di-n-propylaminotetralin (DK-118) in the cat

    International Nuclear Information System (INIS)

    Koons, J.C.

    1985-01-01

    The dopamine receptor agonist 5-hydroxy-6-methyl-2-di-n-propylaminotetralin (DK-118) lowers blood pressure, heart rat and inhibits tachycardia induced in cats by electrical stimulation of sympathetic nerves innervating the heart. DK-118, unlike most of its chemically related dopaminergic analogs, exhibits a slow onset of activity suggesting that one or more metabolites of the drug may be responsible for its pharmacologic effects. The purpose of the work described in this thesis was to gain information regarding the possible bioactivation of DK-118 in cats. In one series of experiments, cats were pretreated with inhibitors of drug metabolism, metyrapone or SKF 525-A, and alterations of the pharmacologic effects of DK-118 determined. A high-performance liquid chromatography assay-using electrochemical detection was developed to quantify urine and plasma concentrations of DK-118 in control, metyrapone pretreated and SKF 525-A pretreated cats. Urinary metabolites of [ 14 C]DK-118 were identified employing HPLC, GC/MS and FAB/MS. Pharmacologic activity and receptor binding of selected metabolites were determined. Data presented in this thesis are consistent with the hypothesis that metabolites contribute to some of the pharmacologic effects of DK-118

  4. Pharmacological analysis of paregoric elixir and its constituents: in vitro and in vivo studies.

    Science.gov (United States)

    Andrade, Edinéia Lemos; Ferreira, Juliano; Santos, Adair R S; Calixto, João B

    2007-11-01

    Paregoric elixir is a phytomedicinal product which is used widely as an analgesic, antispasmodic and antidiarrheal agent. Here, we investigated the pharmacological actions and some of the mechanisms of action of paregoric elixir and compared its action with some of its components, the alkaloids morphine and papaverine. The paregoric elixir given orally to mice did not present relevant toxic effects, even when administered in doses up to 2000-fold higher than those used clinically. However, it showed an antinociceptive action that was more potent, but less efficacious, than morphine. In contrast to morphine, its effect was not dose-dependent and not reversed by the non-selective opioid antagonist naloxone. Moreover, paregoric elixir produced tolerance, but did not cause cross-tolerance, with the antinociceptive actions of morphine. When assessed in the gastrointestinal motility in vivo, paregoric elixir elicited graduated reduction of gastrointestinal transit. Finally, like morphine and papaverine, paregoric elixir concentration-dependently inhibited electrically-induced contraction of the guinea pig isolated ileum. In vivo and in vitro gastrointestinal actions of paregoric elixir were not reversed by naloxone. Collectively, the present findings lead us to suggest that the pharmacological actions produced by paregoric elixir are probably due to a synergic action of its constituents.

  5. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases...

  6. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion...

  7. Pharmacology of human experimental anxiety

    Directory of Open Access Journals (Sweden)

    F.G. Graeff

    2003-04-01

    Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  8. Carotenoids: biochemistry, pharmacology and treatment.

    Science.gov (United States)

    Milani, Alireza; Basirnejad, Marzieh; Shahbazi, Sepideh; Bolhassani, Azam

    2017-06-01

    Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

  9. A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat.

    Directory of Open Access Journals (Sweden)

    Maïte Hotte

    Full Text Available BACKGROUND: We aimed to further understand the relationship between cAMP concentration and mnesic performance. METHODS AND FINDINGS: Rats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p., rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p. and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p. before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold, prefrontal (1.3 fold and perirhinal (1.3 fold cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold from drug-treated rats (except for milrinone+RS 67333 treatment. After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold and the perirhinal cortex (2.1 fold from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold and milrinone (respectively 1.46 fold and 1.56 fold-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h. CONCLUSIONS: Our results strongly suggest that a "pre-sample" early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.

  10. Copper, cadmium, and zinc concentrations in juvenile Chinook salmon and selected fish-forage organisms (aquatic insects) in the upper Sacramento River, California

    Science.gov (United States)

    Saiki, Michael K.; Martin, Barbara A.; Thompson, Larry D.; Walsh, Daniel

    2001-01-01

    This study assessed the downstream extent andseverity of copper (Cu), cadmium (Cd), and zinc (Zn)contamination from acid mine drainage on juvenile chinook salmon(Oncorhynchus tshawytscha) and aquatic insects over aroughly 270-km reach of the Sacramento River below KeswickReservoir. During April–May 1998, salmon were collected fromfour sites in the river and from a fish hatchery that receiveswater from Battle Creek. Salmon from river sites were examinedfor gut contents to document their consumption of variousinvertebrate taxa, whereas salmon from river sites and thehatchery were used for metal determinations. Midge(Chironomidae) and caddisfly (Trichoptera) larvae and mayfly(Ephemeroptera) nymphs were collected for metal determinationsduring April–June from river sites and from Battle and Buttecreeks. The fish hatchery and Battle and Butte creeks served asreference sites because they had no history of receiving minedrainage. Salmon consumed mostly midge larvae and pupae (44.0%,damp-dry biomass), caddisfly larvae (18.9%), Cladocera (5.8%),and mayfly nymphs (5.7%). These results demonstrated thatinsects selected for metal determinations were important as fishforage. Dry-weight concentrations of Cu, Cd, and Zn weregenerally far higher in salmon and insects from the river thanfrom reference sites. Within the river, high metalconcentrations persisted as far downstream as South Meridian (thelowermost sampling site). Maximum concentrations of Cd (30.7 μg g-1) and Zn (1230 μg g-1),but not Cu (87.4 μg g-1), in insects exceeded amounts that other investigators reported as toxic when fed for prolonged periods to juvenile salmonids.

  11. The effect of feed supplementation with zinc chelate and zinc sulphate on selected humoral and cell-mediated immune parameters and cytokine concentration in broiler chickens.

    Science.gov (United States)

    Jarosz, Łukasz; Marek, Agnieszka; Grądzki, Zbigniew; Kwiecień, Małgorzata; Kalinowski, Marcin

    2017-06-01

    The ability of poultry to withstand infectious disease caused by bacteria, viruses or protozoa depends upon the integrity of the immune system. Zinc is important for proper functioning of heterophils, mononuclear phagocytes and T lymphocytes. Numerous data indicate that the demand for zinc in poultry is not met in Poland due to its low content in feeds of vegetable origin. The aim of the study was to determine the effect of supplementation of inorganic (ZnSO 4 and ZnSO 4 + phytase enzyme), and organic forms of zinc (Zn with glycine and Zn with glycine and phytase enzyme) on selected parameters of the cellular and humoral immune response in broiler chickens by evaluating the percentage of CD3 + CD4 + , CD3 + CD8 + , CD25 + , MHC Class II, and BU-1 + lymphocytes, the phagocytic activity of monocytes and heterophils, and the concentration of IL-2, IL-10 and TNF-α in the peripheral blood. Flow cytometry was used to determine selected cell-mediated immune response parameters. Phagocytic activity in whole blood was performed using the commercial Phagotest kit (ORPEGEN-Pharma, Immuniq, Poland). The results showed that supplementation with zinc chelates causes activation of the cellular and humoral immune response in poultry, helping to maintain the balance between the Th1 and Th2 response and enhancing resistance to infections. In contrast with chelates, the use of zinc in the form of sulphates has no immunomodulatory effect and may contribute to the development of local inflammatory processes in the digestive tract, increasing susceptibility to infection. Copyright © 2016. Published by Elsevier Ltd.

  12. Justification for Selecting Level A vs. Level B Personal Protective Equipment to Remediate a Room Containing Concentrated Acids, Bases and Radiological Constituents

    International Nuclear Information System (INIS)

    Hylko, J. M.; Thompson, A. L.; Walter, J. F.; Deecke, T. A.

    2002-01-01

    Selecting the appropriate personal protective equipment (PPE) is based on providing an adequate level of employee protection relative to the task-specific conditions and hazards. PPE is categorized into four ensembles, based on the degree of protection afforded; e.g., Levels A (most restrictive), B, C, and D (least restrictive). What is often overlooked in preparing an ensemble is that the PPE itself can create significant worker hazards; i.e., the greater the level of PPE, the greater the associated risks. Furthermore, there is confusion as to whether a more ''conservative approach'' should always be taken since Level B provides the same level of respiratory protection as Level A but less skin protection. This paper summarizes the Occupational Safety and Health Administration regulations addressing Level A versus Level B, and provides justification for selecting Level B over Level A without under-protecting the employee during a particular remediation scenario. The scenario consisted of an entry team performing (1) an initial entry into a room containing concentrated acids (e.g., hydrofluoric acid), bases, and radiological constituents; (2) sampling and characterizing container contents; and (3) retrieving characterized containers. The invasive nature of the hydrofluoric acid sampling and characterization scenario created a high potential for splash, immersion, and exposure to hazardous vapors, requiring additional skin protection. The hazards associated with this scenario and the chemical nature of hydrofluoric acid provided qualitative evidence to justify Level A. Once the hydrofluoric acid was removed from the room, PPE performance was evaluated against the remaining chemical inventory. If chemical breakthrough from direct contact was not expected to occur and instrument readings confirmed the absence of any hazardous vapors, additional skin protection afforded by wearing a vapor-tight, totally-encapsulated suit was not required. Therefore, PPE performance and

  13. Pharmacologic treatment of depression in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus W.; Glazenborg, Arjon; Uyttenboogaart, Maarten; Mostert, Jop; De Keyser, Jacques

    2011-01-01

    Background Depression is a common problem in patients with multiple sclerosis (MS). It is unclear which pharmacologic treatment is the most effective and the least harmful. Objectives To investigate the efficacy and tolerability of pharmacologic treatments for depression in patients with MS. Search

  14. Complex Pharmacology of Free Fatty Acid Receptors

    DEFF Research Database (Denmark)

    Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond

    2017-01-01

    pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or "free" fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets...

  15. The Dutch vision of clinical pharmacology

    NARCIS (Netherlands)

    Schellens, J H M; Grouls, R; Guchelaar, H J; Touw, D J; Rongen, G A; de Boer, A; Van Bortel, L M

    Recent position papers addressing the profession of clinical pharmacology have expressed concerns about the decline of interest in the field among clinicians and medical educators in the United Kingdom and other Western countries, whether clinical pharmacology is actually therapeutics, and whether

  16. Pharmacology of sexually compulsive behavior.

    Science.gov (United States)

    Codispoti, Victoria L

    2008-12-01

    In a meta-analysis on controlled outcomes evaluations of 22,000 sex offenders, Losel and Schmucker found 80 comparisons between treatment and control groups. The recidivism rate averaged 19% in treated groups, and 27% in controls. Most other reviews reported a lower rate of sexual recidivism in treated sexual offenders. Of 2039 citations in this study (including literature in five languages), 60 studies held independent comparisons. Problematic issues included the control groups; various hormonal, surgical, cognitive behavioral, and psychotherapeutic treatments; and sample sizes. In the 80 studies compared after the year 2000, 32% were reported after 2000, 45% originated in the United States, 45% were reported in journals, and 36% were unpublished. Treatment characteristics showed a significant lack of pharmacologic treatment (7.5%), whereas use cognitive and classical behavioral therapy was 64%. In 68% of the studies, no information was available on the integrity of the treatment implementation; 36% of the treatment settings were outpatient only, 31% were prison settings, and 12% were mixed settings (prison, hospital, and outpatient). Integrating research interpretations is complicated by the heterogeneity of sex offenders, with only 56% being adult men and 17.5% adolescents. Offense types reported included 74% child molestation, 48% incest, and 30% exhibitionism. Pedophilia was not singled out. Follow-up periods varied from 12 months to greater than 84 months. The definition of recidivism ran the gamut from arrest (24%), conviction (30%), charges (19%), and no indication (16%). Results were difficult to interpret because of the methodological problems with this type of study. Overall, a positive outcome was noted with sex offender treatment. Cognitive-behavioral and hormonal treatment were the most promising. Voluntary treatment led to a slightly better outcome than mandatory participation. When accounting for a low base rate of sexual recidivism, the reduction

  17. Performance and selectivity of PtxSn/C electro-catalysts for ethanol oxidation prepared by reduction with different formic acid concentrations

    International Nuclear Information System (INIS)

    Zignani, Sabrina C.; Baglio, Vincenzo; Linares, José J.; Monforte, Giuseppe; Gonzalez, Ernesto R.; Aricò, Antonino S.

    2012-01-01

    Carbon supported Pt–Sn catalysts were prepared by reduction of Pt and Sn precursors with formic acid and characterized in terms of structure, morphology and surface properties. The electrocatalytic activity for ethanol oxidation was studied in a direct ethanol fuel cell (DEFC) at 70 °C and 90 °C. Electrochemical and physico-chemical data indicated that a proper balance of Pt and Sn species in the near surface region was necessary to maximize the reaction rate. The best atomic surface composition, in terms of electrochemical performance, was Pt:Sn 65:35 corresponding to a bulk composition 75:25 namely Pt 3 Sn 1 /C. The reaction products of ethanol electro-oxidation in single cell and their distribution as a function of the nature of catalyst were determined. Essentially, acetaldehyde and acetic acid were detected as the main reaction products; whereas, a lower content of CO 2 was formed. The selectivity toward acetic acid vs. acetaldehyde increased with the increase of the Sn content and decreased by decreasing the concentration of the reducing agent used in the catalyst preparation. According to the recent literature, these results have been interpreted on the basis of ethanol adsorption characteristics and ligand effects occurring for Sn-rich electrocatalysts.

  18. Phytochemical and pharmacological properties of essential oils from Cedrus species.

    Science.gov (United States)

    Saab, Antoine M; Gambari, Roberto; Sacchetti, Gianni; Guerrini, Alessandra; Lampronti, Ilaria; Tacchini, Massimo; El Samrani, Antoine; Medawar, Samir; Makhlouf, Hassane; Tannoury, Mona; Abboud, Jihad; Diab-Assaf, Mona; Kijjoa, Anake; Tundis, Rosa; Aoun, Jawad; Efferth, Thomas

    2018-06-01

    Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.

  19. Future pharmacological therapy in hypertension.

    Science.gov (United States)

    Stewart, Merrill H; Lavie, Carl J; Ventura, Hector O

    2018-04-26

    Hypertension (HTN) is a widespread and growing disease, with medication intolerance and side-effect present among many. To address these obstacles novel pharmacotherapy is an active area of drug development. This review seeks to explore future drug therapy for HTN in the preclinical and clinical arenas. The future of pharmacological therapy in HTN consists of revisiting old pathways to find new targets and exploring wholly new approaches to provide additional avenues of treatment. In this review, we discuss the current status of the most recent drug therapy in HTN. New developments in well trod areas include novel mineralocorticoid antagonists, aldosterone synthase inhibitors, aminopeptidase-A inhibitors, natriuretic peptide receptor agonists, or the counter-regulatory angiotensin converting enzyme 2/angiotensin (Ang) (1-7)/Mas receptor axis. Neprilysin inhibitors popularized for heart failure may also still hold HTN potential. Finally, we examine unique systems in development never before used in HTN such as Na/H exchange inhibitors, vasoactive intestinal peptide agonists, and dopamine beta hydroxylase inhibitors. A concise review of future directions of HTN pharmacotherapy.

  20. [History and pharmacology of trazodone].

    Science.gov (United States)

    Agnoli, A

    1986-10-01

    Trazodone, a non-tricyclic molecule, represents the first of a new generation of antidepressants. It is currently marketed in a number of European countries, in the United States and in Latin America. The pharmacological and biochemical data, the mechanism of action and the preferential indications of trazodone are presented and compared to those of imipramine and other tricyclics. Unlike imipramine, trazodone inhibits the adrenergic system. The two molecules have anti-nociceptive properties, similar effects on the serotoninergic system and, after repeated administrations, they both reduce the density of beta-receptors. The clinical implications of the alpha-blocking activity of trazodone are reported. Trazodone is preferable to tricyclic anti-depressants in the treatment of depression in elderly subjects in general, and especially when they present closed angle glaucoma, prostatic hypertrophy, tremor or cardiovascular problems due to hyperactivity of the adrenergic system, as well as in organic depressions and in depression secondary to schizophrenia, alcoholism and in patients with Parkinson's disease.

  1. Cardiovascular Safety Pharmacology of Sibutramine.

    Science.gov (United States)

    Yun, Jaesuk; Chung, Eunyong; Choi, Ki Hwan; Cho, Dae Hyun; Song, Yun Jeong; Han, Kyoung Moon; Cha, Hey Jin; Shin, Ji Soon; Seong, Won-Keun; Kim, Young-Hoon; Kim, Hyung Soo

    2015-07-01

    Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

  2. Pharmacological challenges in chronic pancreatitis.

    Science.gov (United States)

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-11-14

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids are often prescribed as pain treatment. Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time. Furthermore, the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug. As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis. The factors may not have clinical relevance, but may explain inter-individual variations in responses to a given drug, in patients with chronic pancreatitis.

  3. [Pharmacologic treatment of osteoporosis--2011].

    Science.gov (United States)

    Lakatos, Péter

    2011-08-14

    Osteoporosis affects approximately 9% of the population in Hungary resulting in about 100 000 osteoporotic fractures annually. Thirty-five percent of patients with hip fractures due to osteoporosis will die within 1 year. Direct costs of osteoporosis exceed 25 billion forints per year. Apparently, cost-effective reduction of bone loss and consequent fracture risk will add up to not only financial savings but improvement in quality of life, as well. A number of pharmacological modalities are available for this purpose. The mainstay of the treatment of osteoporosis is the bisphosphonate group that includes effective anti-resorptive compounds mitigating bone loss and fragility. The recently registered denosumab exhibits similar efficacy by neutralizing RANK ligand, however, marked differences can be observed between the two drug classes. Strontium has a unique mechanism of action by rebalancing bone turnover, and thus, providing an efficient treatment option for the not fast bone losers who are at high fracture risk. The purely anabolic teriparatide is available for the extremely severe osteoporotic patients and for those who do not respond to other types of therapy. Older treatment options such as hormone replacement therapy, raloxifene, tibolone or calcitonin may also have a restricted place in the management of osteoporosis.

  4. Safety pharmacology — Current and emerging concepts

    International Nuclear Information System (INIS)

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas

    2013-01-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests

  5. Safety pharmacology — Current and emerging concepts

    Energy Technology Data Exchange (ETDEWEB)

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Atkinson, Jeffrey [Lorraine University Pharmacolor Consultants Nancy PCN (France); Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Delaunois, Annie [UCB Pharma (Belgium); Dermody, Ailsa; Govindappa, Karthik [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Guillon, Jean-Michel [Sanofi-aventis (France); Jenkins, Rosalind [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Kenna, Gerry [Astra-Zeneca (United Kingdom); Lemmer, Björn [Ruprecht-Karls-Universität Heidelberg (Germany); Meecham, Ken [Huntingdon Life Sciences (United Kingdom); Olayanju, Adedamola [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Pestel, Sabine [Boehringer-Ingelheim (Germany); Rothfuss, Andreas [Roche (Switzerland); and others

    2013-12-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests.

  6. Investigation of Elemental Mass Spectrometry in Pharmacology for Peptide Quantitation at Femtomolar Levels.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Cordeau

    Full Text Available In the search of new robust and environmental-friendly analytical methods able to answer quantitative issues in pharmacology, we explore liquid chromatography (LC associated with elemental mass spectrometry (ICP-MS to monitor peptides in such complex biological matrices. The novelty is to use mass spectrometry to replace radiolabelling and radioactivity measurements, which represent up-to now the gold standard to measure organic compound concentrations in life science. As a proof of concept, we choose the vasopressin (AVP/V1A receptor system for model pharmacological assays. The capacity of ICP-MS to provide highly sensitive quantitation of metallic and hetero elements, whatever the sample medium, prompted us to investigate this technique in combination with appropriate labelling of the peptide of interest. Selenium, that is scarcely present in biological media, was selected as a good compromise between ICP-MS response, covalent tagging ability using conventional sulfur chemistry and peptide detection specificity. Applying selenium monitoring by elemental mass spectrometry in pharmacology is challenging due to the very high salt content and organic material complexity of the samples that produces polyatomic aggregates and thus potentially mass interferences with selenium detection. Hyphenation with a chromatographic separation was found compulsory. Noteworthy, we aimed to develop a straightforward quantitative protocol that can be performed in any laboratory equipped with a standard macrobore LC-ICP-MS system, in order to avoid time-consuming sample treatment or special implementation of instrumental set-up, while allowing efficient suppression of all mass interferences to reach the targeted sensitivity. Significantly, a quantification limit of 57 ng Se L-1 (72 femtomoles of injected Se was achieved, the samples issued from the pharmacological assays being directly introduced into the LC-ICP-MS system. The established method was successfully

  7. Pharmacology and crystal structure of novel 2,3-quinoxalinediones at kainate receptors

    DEFF Research Database (Denmark)

    Møllerud, Stine; Pallesen, Jakob Staun; Pasini, Diletta

    2017-01-01

    , within the KA receptor family (GluK1-5) only compounds with selectivity towards GluK1 exist [1]. Thus, there is an unmet need for Tool compounds with selectivity towards the remaining KA receptor subunits. Here we report the pharmacology of a series of novel N1-substituted 2,3-quinoxalinediones, as well....... Functional electrophysiological (TEVC) experiments indeed showed these compounds to be antagonists at cloned, homomeric KA receptors. The structure and pharmacology will be valuable for design of new and more GluK3-selective quinoxalinedione analogues....

  8. Concentrations, loads, and yields of select constituents from major tributaries of the Mississippi and Missouri Rivers in Iowa, water years 2004-2008

    Science.gov (United States)

    Garrett, Jessica D.

    2012-01-01

    Excess nutrients, suspended-sediment loads, and the presence of pesticides in Iowa rivers can have deleterious effects on water quality in State streams, downstream major rivers, and the Gulf of Mexico. Fertilizer and pesticides are used to support crop growth on Iowa's highly productive agricultural landscape and for household and commercial lawns and gardens. Water quality was characterized near the mouths of 10 major Iowa tributaries to the Mississippi and Missouri Rivers from March 2004 through September 2008. Stream loads were calculated for select ions, nutrients, and sediment using approximately monthly samples, and samples from storm and snowmelt events. Water-quality samples collected using standard streamflow-integrated protocols were analyzed for major ions, nutrients, carbon, pesticides, and suspended sediment. Statistical data summaries of sample data used parametric and nonparametric techniques to address potential bias related to censored data and multiple levels of censoring of data below analytical detection limits. Constituent stream loads were computed using standard pre-defined models in S-LOADEST that include streamflow and time terms plus additional terms for streamflow variability and streamflow anomalies. Streamflow variability terms describe the difference in streamflow from recent average conditions, whereas streamflow anomaly terms account for deviations from average conditions from long- to short-term sequentially. Streamflow variability or anomaly terms were included in 44 of 80 site/constituent individual models, demonstrating the usefulness of these terms in increasing accuracy of the load estimates. Constituent concentrations in Iowa streams exhibit streamflow, seasonal, and spatial patterns related to the landform and climate gradients across the studied basins. The streamflow-concentration relation indicated dilution for ions such as chloride and sulfate. Other constituent concentrations, such as dissolved organic carbon and

  9. Pharmacological interventions for antisocial personality disorder.

    Science.gov (United States)

    Khalifa, Najat; Duggan, Conor; Stoffers, Jutta; Huband, Nick; Völlm, Birgit A; Ferriter, Michael; Lieb, Klaus

    2010-08-04

    Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance misuse, unemployment, homelessness and relationship difficulties. To evaluate the potential beneficial and adverse effects of pharmacological interventions for people with AsPD. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to September 2009), EMBASE (1980 to 2009, week 37), CINAHL (1982 to September 2009), PsycINFO (1872 to September 2009) , ASSIA (1987 to September 2009) , BIOSIS (1985 to September 2009), COPAC (September 2009), National Criminal Justice Reference Service Abstracts (1970 to July 2008), Sociological Abstracts (1963 to September 2009), ISI-Proceedings (1981 to September 2009), Science Citation Index (1981 to September 2009), Social Science Citation Index (1981 to September 2009), SIGLE (1980 to April 2006), Dissertation Abstracts (September 2009), ZETOC (September 2009) and the metaRegister of Controlled Trials (September 2009). Controlled trials in which participants with AsPD were randomly allocated to a pharmacological intervention and a placebo control condition. Two trials comparing one drug against another without a placebo control are reported separately. Three review authors independently selected studies. Two review authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data. Eight studies met the inclusion criteria involving 394 participants with AsPD. Data were available from four studies involving 274 participants with AsPD. No study set out to recruit participants solely on the basis of having AsPD, and in only one study was the sample entirely of AsPD participants. Eight different drugs were examined in eight studies. Study quality was relatively poor. Inadequate reporting meant the data available were generally insufficient to allow any independent statistical analysis. The

  10. Review of the Chemistry and Pharmacology of 7-Methyljugulone ...

    African Journals Online (AJOL)

    Review of the Chemistry and Pharmacology of 7-Methyljugulone. ... Methods: The chemical and pharmacological data were retrieved from the well-known scientific websites such as Pubmed, Google Scholar, Reaxys, Scirus, Scopus, ... Keywords: 7-methyljugulone; biosynthesis; in vitro synthesis; pharmacology

  11. [PROFESSOR VLADIMIR V. NIKOLAEV AND RUSSIAN PHARMACOLOGY.

    Science.gov (United States)

    Bondarchuk, N G; Fisenko, V P

    2016-01-01

    Various stages of scientific research activity of Prof. Vladimir V. Nikolaev are analyzed. The importance of Prof. Nikolaev's discovery of the two-neuron parasympathetic nervous system and some new methods of pharmacological substances evaluation is shown. Prof. Nikolaev is known as the editor of the first USSR Pharmacopoeia. Peculiarities of pharmacology teaching at the First Moscow Medical institute under conditions of changing social demands are described. Successful research of Prof. Nikolaev with colleagues in studying new mechanisms of drug action and developing original pharmacological substances is summarized.

  12. Problems of pharmacological supply of disaster medicine

    International Nuclear Information System (INIS)

    Sabaev, V.V.; Il'ina, S.L.

    1995-01-01

    The paper reviews a number of pharmacological problems, being important for the disaster medicine, of theoretical and practical nature, the settlement of which would promote more efficient rendering emergency medical aid to the injured persons in the conditions of emergency situations and further expert medical care. On the example of radiation accidents there are studied methodical approaches to organization of drug prophylaxis and therapy of the injured persons in emergency situations. The authors have proved the necessity of arranging proper pharmacological supply of disaster medicine which is to settle the whole complex of scientific-applied and organizational questions relating to the competence of pharmacology and pharmacy. 17 refs

  13. [Contribution of animal experimentation to pharmacology].

    Science.gov (United States)

    Sassard, Jean; Hamon, Michel; Galibert, Francis

    2009-11-01

    Animal experimentation is of considerable importance in pharmacology and cannot yet be avoided when studying complex, highly integrated physiological functions. The use of animals has been drastically reduced in the classical phases of pharmacological research, for example when comparing several compounds belonging to the same pharmacological class. However, animal experiments remain crucial for generating and validating new therapeutic concepts. Three examples of such research, conducted in strict ethical conditions, will be used to illustrate the different ways in which animal experimentation has contributed to human therapeutics.

  14. Concentration data for anthropogenic organic compounds in ground water, surface water, and finished water of selected community water systems in the United States, 2002-05

    Science.gov (United States)

    Carter, Janet M.; Delzer, Gregory C.; Kingsbury, James A.; Hopple, Jessica A.

    2007-01-01

    combustion-derived compounds; (10) personal care and domestic use products; (11) plant- or animal-derived biochemicals; (12) refrigerants and propellants; and (13) solvents. Source and finished water samples were collected during phase 2 and analyzed for constituents that were detected frequently during phase 1. This report presents concentration data for AOCs in ground water, surface water, and finished water of CWSs sampled for SWQA studies during 2002-05. Specifically, this report presents the analytical results of samples collected during phase 1 including (1) samples from 221 wells that were analyzed for 258 AOCs; (2) monthly samples from 9 surface-water sites that were analyzed for 258 AOCs during phase 1; and (3) samples from a subset of the wells and surface-water sites located in areas with substantial agricultural production that were analyzed for 3 additional pesticides and 16 pesticide degradates. Samples collected during phase 2 were analyzed for selected AOCs that were detected most frequently in source water during phase 1 sampling; analytical results for phase 2 are presented for (1) samples of source water and finished water from 94 wells; and (2) samples of source water and finished water samples that were collected monthly and during selected flow conditions at 8 surface-water sites. Results of quality-assurance/quality-control samples collected for SWQA studies during 2002-05 also are presented.

  15. Classification of archaeological pieces into their respective stratum by a chemometric model based on the soil concentration of 25 selected elements

    International Nuclear Information System (INIS)

    Carrero, J.A.; Goienaga, N.; Fdez-Ortiz de Vallejuelo, S.; Arana, G.; Madariaga, J.M.

    2010-01-01

    The aim of this work was to demonstrate that an archaeological ceramic piece has remained buried underground in the same stratum for centuries without being removed. For this purpose, a chemometric model based on Principal Component Analysis, Soft Independent Modelling of Class Analogy and Linear Discriminant Analysis classification techniques was created with the concentration of some selected elements of both soil of the stratum and soil adhered to the ceramic piece. Some ceramic pieces from four different stratigraphic units, coming from a roman archaeological site in Alava (North of Spain), and its respective stratum soils were collected. The soil adhered to the ceramic pieces was removed and treated in the same way as the soil from its respective stratum. The digestion was carried out following the US Environmental Pollution Agency EPA 3051A method. A total of 54 elements were determined in the extracts by a rapid screening inductively coupled plasma mass spectrometry method. After rejecting the major elements and those which could have changed from the original composition of the soils (migration or retention from/to the buried objects), the following elements (25) were finally taken into account to construct the model: Li, V, Co, As, Y, Nb, Sn, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Au, Th and U. A total of 33 subsamples were treated from 10 soils belonging to 4 different stratigraphic units. The final model groups and discriminate them in four groups, according to the stratigraphic unit, having both the stratum and soils adhered to the pieces falling down in the same group.

  16. Background concentrations of selected radionuclides, organic compounds, and chemical constituents in ground water in the vicinity of the Idaho National Engineering Laboratory

    International Nuclear Information System (INIS)

    Orr, B.R.; Cecil, L.D.; Knobel, L.L.

    1991-01-01

    Background concentrations of radionuclides, organic compounds, and other chemical constituents in water in the Snake River Plain aquifer in Idaho were estimated from groundwater sample analyses. Detectable concentrations of transuranic elements should not be present in water from the Snake River Plain aquifer. Background concentrations of tritium generally range from 75 to 150 pCi/L. Strontium-90 and iodine-129 concentrations generally are 0 and from 0.05 pCi/L, respectively. At the INEL, comparison of the mean and median concentrations of tritium, strontium-90, and iodine-129 indicates that operations locally have affected concentrations in groundwater. Gross alpha-particle and beta-particle radioactivity in water from the Snake River Plain aquifer ranges from 0 to 5 pCi/L and 0 to 8 pCi/L, respectively. Background gamma radiation in groundwater is attributed to cesium-137, cobalt-60, and potassium-40. Cesium-137 and cobalt-60 concentrations generally are zero in groundwater at the INEL. Naturally occurring concentrations of potassium-40 probably are about 300 pCi/L. Background concentrations of organic compounds in water from the Snake River Plain aquifer generally are less than 0.2 microg/L. Background arsenic and chromium concentrations both are about 2 to 3 microg/L. Barium concentrations are from about 50 to about 70 microg/L. Lead and mercury concentrations generally are less than 5 microg/L and 0.1 microg/L, respectively. Cadmium, selenium, and silver concentrations generally are less than 1 microg/L. Nitrate concentrations range from 0 to about 1.4 mg/L

  17. Phytochemical and pharmacological overview on Liriopes radix

    African Journals Online (AJOL)

    Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee. University ... has been used as a therapeutic drug for the treatment of ..... Alzheimer's disease (AD) is characterized by.

  18. Ethnobotanical, phytochemical and pharmacological properties of ...

    African Journals Online (AJOL)

    Electronic search engines such as Google, Google scholar, publishing sites such as Elsevier .... A number of pharmacological activities of C. bulbispermum have been ..... bulbispermum using the direct plate method and minimum inhibitory ...

  19. Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

    NARCIS (Netherlands)

    Heine, R. ter

    2009-01-01

    The aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment.

  20. Medicinal, Pharmacological and Phytochemical Potentials of ...

    African Journals Online (AJOL)

    Medicinal, Pharmacological and Phytochemical Potentials of Annona Comosus linn. ... Therapeutic plants, and the drugs derived from them, are the most important ... also as treatment to: diarrhea, indigestion, pneumonia, bronchitis, arthritis, ...

  1. Disrupting reconsolidation: pharmacological and behavioral manipulations

    NARCIS (Netherlands)

    Soeter, M.; Kindt, M.

    2011-01-01

    We previously demonstrated that disrupting reconsolidation by pharmacological manipulations "deleted" the emotional expression of a fear memory in humans. If we are to target reconsolidation in patients with anxiety disorders, the disruption of reconsolidation should produce content-limited

  2. Pharmaceutical and pharmacological approaches for bioavailability

    Indian Academy of Sciences (India)

    2014-01-27

    Jan 27, 2014 ... Etoposide posses high plasma protein binding (97%) and is degraded via ... The present article gives insight on pharmaceutical and pharmacological .... caprolactone and were found efficient as drug delivery vehicles.

  3. ORIGINAL ARTICLES Pharmacological testing in Horner's syndrome

    African Journals Online (AJOL)

    topical cocaine 10% in both eyes gave an odds ratio of 1 050:1 that. Horner's syndrome ... nerve endings and therefore do not stimulate the effector cells directly. ... Pharmacological testing in Horner's syndrome – a new paradigm. Derrick P ...

  4. 2011 Annual Meeting of the Safety Pharmacology Society: an overview.

    Science.gov (United States)

    Cavero, Icilio

    2012-03-01

    The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization

  5. Advances in the nutritional and pharmacological management of phenylketonuria

    Science.gov (United States)

    Ney, Denise M.; Blank, Robert D.; Hansen, Karen E.

    2014-01-01

    Structural Abstract Purpose of review The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU). Recent findings Glycomacropeptide (GMP), a whey protein produced during cheese production, is a low-phe intact protein that represents a new dietary alternative to synthetic amino acids (AAs) for people with PKU. Skeletal fragility is a long-term complication of PKU that based on murine research, appears to result from both genetic and nutritional factors. Skeletal fragility in murine PKU is attenuated with the GMP diet, compared with an AA diet, allowing greater radial bone growth. Pharmacologic therapy with tetrahydrobiopterin (BH4), acting as a molecular chaperone for phenylalanine hydroxylase, increases tolerance to dietary phe in some individuals. Large neutral AAs (LNAA) inhibit phe transport across the intestinal mucosa and blood brain barrier; LNAA are most effective for individuals unable to comply with the low-phe diet. Summary Although a low-phe synthetic AA diet remains the mainstay of PKU management, new nutritional and pharmacological treatment options offer alternative approaches to maintain lifelong low phe concentrations. GMP medical foods provide an alternative to AA formula that may improve bone health, and BH4 permits some individuals with PKU to increase tolerance to dietary phe. Further research is needed to characterize the long-term efficacy of these new approaches for PKU management. PMID:24136088

  6. Pharmacological activities of Vitex agnus-castus extracts in vitro.

    Science.gov (United States)

    Meier, B; Berger, D; Hoberg, E; Sticher, O; Schaffner, W

    2000-10-01

    The pharmacological effects of ethanolic Vitex agnus-castus fruit-extracts (especially Ze 440) and various extract fractions of different polarities were evaluated both by radioligand binding studies and by superfusion experiments. A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL. Binding, neither to the histamine H1, benzodiazepine and OFQ receptor, nor to the binding-site of the serotonin (5-HT) transporter, was significantly inhibited. The lipophilic fractions contained the diterpenes rotun-difuran and 6beta,7beta-diacetoxy-13-hydroxy-labda-8,14-dien . They exhibited inhibitory actions on dopamine D2 receptor binding. While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction. Standardised Ze 440 extracts of different batches were of constant pharmacological quality according to their potential to inhibit the binding to D2 receptors. In superfusion experiments, the aqueous fraction of a methanolic extract inhibited the release of acetylcholine in a concentration-dependent manner. In addition, the potent D2 receptor antagonist spiperone antagonised the effect of the extract suggesting a dopaminergic action mediated by D2 receptor activation. Our results indicate a dopaminergic effect of Vitex agnus-castus extracts and suggest additional pharmacological actions via opioid receptors.

  7. Punishment, Pharmacological Treatment, and Early Release

    DEFF Research Database (Denmark)

    Ryberg, Jesper

    2013-01-01

    Recent studies have shown that pharmacological treatment may have an impact on aggressive and impulsive behavior. Assuming that these results are correct, would it be morally acceptable to instigate violent criminals to accept pharmacological rehabilitation by offering this treatment in return fo...... relates to the acceptability of the fact that those criminals who accepted the treatment would be exempted from the punishment they rightly deserved. It is argued that none of these reasons succeeds in rejecting this sort of offer....

  8. The pharmacological assay as a tool to medicinal plants domestication

    Directory of Open Access Journals (Sweden)

    Montanari Jr., Ilio

    2016-07-01

    Full Text Available In Brazil studies with native medicinal plants are usually performed using non-domesticated plants and as a result the genetic variability of wild species could express different levels of active principles changing their therapeutic effect. Based on that, the aim of this study was to demonstrate that extract of different half- sib families Cordia verbenacea (DC, widely used as medicinal plant in Brazil, have different efficacy in the Total Growth Inhibition (TGI of 5 different human tumor cell lines. Data were statistically analyzed using ANOVA follow by Tuckey test and a heritability estimation of the plant families was performed. The results showed that TGI are different for each plant family according with each human tumor cell line. For instance, extracts obtained from families 3,11 and 12 were more effective to inhibit the U-251 and Ht-29 cell lines compared to the other families, while extracts obtained from the family 32 was more effective against thethe PC-3 line. The heritability coefficient indicated that plant population selection could promote a genetic improvement related to its active principle and their pharmacological effect and could provide the identification of the best families according to their pharmacological efficacy. In conclusion, this study suggests that the domestication of a wild medicinal plant should be better monitored by its pharmacological effect.

  9. Randomised controlled trials of psychological & pharmacological treatments for body dysmorphic disorder: A systematic review.

    Science.gov (United States)

    Phillipou, Andrea; Rossell, Susan L; Wilding, Helen E; Castle, David J

    2016-11-30

    Treatment for body dysmorphic disorder (BDD) often involves a combination of psychological and pharmacological interventions. However, only a small number of randomised controlled trials (RCTs) have been undertaken examining the efficacy of different therapeutic interventions. The aim of this study was to systematically review the RCTs involving psychological and pharmacological interventions for the treatment of BDD. The literature was searched to June 2015, and studies were included if they were written in English, empirical research papers published in peer-review journals, specifically assessed BDD patients, and involved a RCT assessing BDD symptoms pre- and post-intervention. Nine studies were identified: six involving psychological and three involving pharmacological interventions. Cognitive behaviour therapy, metacognitive therapy and selective serotonin reuptake inhibitors were identified as treatments with potential benefit. The small number of RCTs and the heterogeneity of findings emphasises the need for more high quality RCTs assessing both psychological and pharmacological interventions for BDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Pharmacological interventions for acute pancreatitis.

    Science.gov (United States)

    Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

    2017-04-21

    In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin

  11. An overview on Phyllanthus emblica: phytochemical and pharmacological investigations

    Directory of Open Access Journals (Sweden)

    Y. Amirazodi

    2017-11-01

    Full Text Available Background and objectives: Phyllanthus emblica L. (Phyllanthaceae, commonly known as Indian gooseberry, is an endemic plant to the tropical and subtropical areas in china, India and Thailand. The plant is extensively used in Chinese, Ayurveda, and traditional Persian medicine (TPM. In addition, there are numerous reports on pharmacological and clinical activities of gooseberry in current medicine. The present review was performed to compile the phytochemical and pharmacological data on P. emblica in order to draw a window for further research.  Methods: Databases such as Scopus, ScienceDirect and PubMed were searched for the term “P. emblica” up to 1st September, 2017. Papers concerning pharmacology and phytochemistry of the plant were gathered and analyzed. On the contrary, agriculture and genetic contents were excluded. Results: Over all, 80 papers were selected. The herb revealed to possess anti-diabetic, anti-oxidant, anti-proliferative, anti-inflammatory, antidepressant, larvicidal, anti-asthmatic, antiulcer, anti-aging, anti-carcinogenic, anti-tumor, anti-genotoxicity, anti-microbial, anticholinergic, antispasmodic, gastroprotective, anti-plasmodia, and antinociceptive activities as well as antidote effect against certain elements. The fruits are also useful in brain and gastrointestinal diseases and can be beneficial in hearth protection. Remarkably, many of those properties have been mentioned in TPM manuscripts.  Conclusion: Despite numerous pharmacological activities for P. emblica, there is still a gap between the in vivo and human studies which should be covered by more comprehensive and complementary studies. Many compounds have been isolated and elucidated from this plant which can be good candidates for various related activities and also as new natural medicaments in novel drug discovery.

  12. Pharmacological Activity and Clinical Use of PDRN

    Directory of Open Access Journals (Sweden)

    Francesco Squadrito

    2017-04-01

    Full Text Available PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout or Oncorhynchus keta (Chum Salmon sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects.

  13. Pharmacological Activity and Clinical Use of PDRN

    Science.gov (United States)

    Squadrito, Francesco; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Minutoli, Letteria; Altavilla, Domenica

    2017-01-01

    PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects. PMID:28491036

  14. Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

    Science.gov (United States)

    Findling, Robert L

    2016-01-01

    Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. © Copyright 2016 Physicians Postgraduate Press, Inc.

  15. An exploratory analysis of the relationship between ambient ozone and particulate matter concentrations during early pregnancy and selected birth defects in Texas

    Science.gov (United States)

    Background: Associations between ozone (O3) and fine particulate matter (PM2.5) concentrations and birth outcomes have been previously demonstrated. We perform an exploratory analysis of O3 and PM2.5 concentrations during early pregnancy and multiple types of birth defects. Met...

  16. Pharmacological stress agents in nuclear cardiology

    International Nuclear Information System (INIS)

    Buscombe, J.R.

    2004-01-01

    Treadmill test combined with myocardial perfusion scintigraphy (MPS) is a commonly used technique in the assessment of coronary artery disease. However there are a group of patients who may not be able to undergo treadmill tests. Patients with underlying conditions like neuromuscular disease, musculoskeletal disorder, heart failure and end-stage renal disease (ESRD) on renal dialysis would find it difficult to perform exercise on a treadmill or bicycle ergometer. These conditions prevent them from performing adequate exercise. Such patients would benefit from pharmacological stress procedures combined with MPS. Nuclear medicine departments use various pharmacological agents while performing stress tests on cardiac patients. The most commonly used pharmacological agents for cardiac stress are coronary vasodilators and catecholamines. In addition to these agents, adjuvant use of nitrates and atropine is also a common practice in nuclear cardiology. This review addresses various physiological and pharmacological properties of the commonly used pharmacological stress agents in MPS and critically analyses their advantages and disadvantages, as well as their safety and efficacy. (author)

  17. Only connect: the merger of BMC Pharmacology and BMC Clinical Pharmacology.

    Science.gov (United States)

    Moylan, Elizabeth C; Morrey, Christopher; Appleford-Cook, Joanne M

    2012-08-13

    This editorial celebrates the launch of BMC Pharmacology and Toxicology within the BMC series of journals published by BioMed Central. The scope of the journal is interdisciplinary encompassing toxicology, experimental and clinical pharmacology including clinical trials. In this editorial we discuss the origins of this new journal and the ethos and policies under which it will operate.

  18. Metal concentrations in selected tissues and main prey species of the annulated sea snake (Hydrophis cyanocinctus) in the Hara Protected Area, northeastern coast of the Persian Gulf, Iran

    International Nuclear Information System (INIS)

    Rezaie-Atagholipour, Mohsen; Riyahi-Bakhtiari, Alireza; Sajjadi, Mirmasoud; Yap, Chee Kong; Ghaffari, Sanaz; Ebrahimi-Sirizi, Zohreh; Ghezellou, Parviz

    2012-01-01

    This study is the first detailed ecotoxicological study of the annulated sea snake, Hydrophis cyanocinctus. Concentrations of lead, cadmium, nickel and vanadium were evaluated in muscle, liver, kidney, skin and blood of the annulated sea snake (H. cyanocinctus) and in the whole bodies of its main prey species (Periophthalmus waltoni and Boleophthalmus dussumieri) in the Hara Protected Area, the Persian Gulf. The mean concentrations of lead and vanadium were highest in the kidney, which identified the kidney as a target organ for metals in sea snakes as it is in other reptilian groups. Mean concentrations of cadmium and nickel were highest in the liver and skin, respectively. Mean cadmium concentrations were significantly higher in the liver compared to prey species, which indicated that prey items may be a source of cadmium for the annulated sea snake in the study area. Data presented here may be considered as a baseline for further ecotoxicological studies in sea snakes.

  19. Temporal changes in nitrogen and phosphorus concentrations with comparisons to conservation practices and agricultural activities in the Lower Grand River, Missouri and Iowa, and selected watersheds, 1969–2015

    Science.gov (United States)

    Krempa, Heather M.; Flickinger, Allison K.

    2017-08-01

    This report presents the results of a cooperative study by the U.S. Geological Survey and Missouri Department of Natural Resources to estimate total nitrogen (TN) and total phosphorus (TP) concentrations at monitoring sites within and near the Lower Grand River hydrological unit. The primary objectives of the study were to quantify temporal changes in TN and TP concentrations and compare those concentrations to conservation practices and agricultural activities. Despite increases in funding during 2011–15 for conservation practices in the Lower Grand River from the Mississippi River Basin Healthy Watersheds Initiative, decreases in flow-normalized TN and TP concentrations during this time at the long-term Grand River site were less than at other long-term sites, which did not receive funding from the Mississippi River Basin Healthy Watersheds Initiative. The relative differences in the magnitude of flow-normalized TN and TP concentrations among long-term sites are directly related to the amount of agricultural land use within the watershed. Significant relations were determined between nitrogen from cattle manure and flow-normalized TN concentrations at selected long-term sites, indicating livestock manure may be a substantial source of nitrogen within the selected long-term site watersheds. Relations between flow-normalized TN and TP concentrations with Conservation Reserve Program acres and with nitrogen and phosphorus from commercial fertilizer indicate that changes in these factors alone did not have a substantial effect on stream TN and TP concentrations; other landscape activities, runoff, within-bank nutrients that are suspended during higher streamflows, or a combination of these have had a greater effect on stream TN and TP concentrations; or there is a lag time that is obscuring relations. Temporal changes in flow-adjusted TN and TP concentrations were not substantial at Lower Grand River Mississippi River Basin Healthy Watersheds Initiative sites

  20. From the Cover: Selective Enhancement of Domoic Acid Toxicity in Primary Cultures of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration.

    Science.gov (United States)

    Pérez-Gómez, Anabel; Cabrera-García, David; Warm, Davide; Marini, Ann M; Salas Puig, Javier; Fernández-Sánchez, Maria Teresa; Novelli, Antonello

    2018-01-01

    Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here, we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was approximately 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+. The enhanced neurotoxic effect of DOM was fully prevented by AMPA/KA receptor antagonist, while N-methyl-D-aspartate-receptor-mediated neurotoxicity did not seem to be involved, as the absence of extracellular Na+ failed to potentiate GLU excitotoxicity under the same experimental conditions. Lowering of extracellular Na+ concentration to 60 mM eliminated extracellular recording of spontaneous electrophysiological activity from cultured neurons grown on a multi electrode array and prevented DOM stimulation of the electrical activity. Although changes in the extracellular Na+ concentration did not alter the magnitude of the rapid increase in intracellular Ca2+ levels associated to DOM exposure, they did change significantly the contribution of voltage-sensitive calcium channels (VScaCs) and the recovery time to baseline. The prevention of Ca2+ influx via VSCaCs by nifedipine failed to prevent DOM toxicity at any extracellular Na+ concentration, while the reduction of extracellular Ca2+ concentration ameliorated DOM toxicity only in the absence of extracellular Na+, enhancing it in physiological conditions. Our data suggest a crucial role for extracellular Na+ concentration in determining excitotoxicity by DOM. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. An exploratory analysis of the relationship between ambient ozone and particulate matter concentrations during early pregnancy and selected birth defects in Texas

    International Nuclear Information System (INIS)

    Vinikoor-Imler, Lisa C.; Stewart, Thomas G.; Luben, Thomas J.; Davis, J. Allen; Langlois, Peter H.

    2015-01-01

    We performed an exploratory analysis of ozone (O 3 ) and fine particulate matter (PM 2.5 ) concentrations during early pregnancy and multiple types of birth defects. Data on births were obtained from the Texas Birth Defects Registry (TBDR) and the National Birth Defects Prevention Study (NBDPS) in Texas. Air pollution concentrations were previously determined by combining modeled air pollution concentrations with air monitoring data. The analysis generated hypotheses for future, confirmatory studies; although many of the observed associations were null. The hypotheses are provided by an observed association between O 3 and craniosynostosis and inverse associations between PM 2.5 and septal and obstructive heart defects in the TBDR. Associations with PM 2.5 for septal heart defects and ventricular outflow tract obstructions were null using the NBDPS. Both the TBDR and the NBPDS had inverse associations between O 3 and septal heart defects. Further research to confirm the observed associations is warranted. - Highlights: • Air pollution concentrations combined modeled air data and air monitoring data. • No associations were observed between the majority of birth defects and PM 2.5 and O 3 . • Estimated associations between PM 2.5 and certain heart defects varied by dataset. • Results were suggestive of an inverse association between O 3 and septal heart defects. • Higher O 3 concentrations may be associated with increased odds of craniosynostosis. - Although most observed associations between ozone and fine particulate matter concentrations and birth defects were null, some were present and warrant further consideration

  2. Assessing pharmacologic and nonpharmacologic risks in candidates for kidney transplantation.

    Science.gov (United States)

    Maldonado, Angela Q; Tichy, Eric M; Rogers, Christin C; Campara, Maya; Ensor, Christopher; Doligalski, Christina T; Gabardi, Steven; Descourouez, Jillian L; Doyle, Ian C; Trofe-Clark, Jennifer

    2015-05-15

    Pharmacotherapy concerns and other factors with a bearing on patient selection for kidney transplantation are discussed. The process of selecting appropriate candidates for kidney transplantation involves multidisciplinary assessment to evaluate a patient's mental, social, physical, financial, and medical readiness for successful surgery and good posttransplantation outcomes. Transplantation pharmacists can play important roles in the recognition and stratification of pharmacologic and nonpharmacologic risks in prospective kidney transplant recipients and the identification of issues that require a mitigation strategy. Key pharmacotherapy-related issues and considerations during the risk assessment process include (1) anticoagulation concerns, (2) cytochrome P-450 isoenzyme-mediated drug interactions, (3) mental health-related medication use, (4) chronic pain-related medication use, (5) medication allergies, (6) use of hormonal contraception and replacement therapy, (7) prior or current use of immunosuppressants, (8) issues with drug absorption, (9) alcohol use, (10) tobacco use, (11) active use of illicit substances, and (12) use of herbal supplements. Important areas of nonpharmacologic risk include vaccine delivery, infection prophylaxis and treatment, and socially related factors such as nonadherent behavior, communication barriers, and financial, insurance, or transportation challenges that can compromise posttransplantation outcomes. Consensus opinions of practitioners in transplantation pharmacy regarding the pharmacologic and nonpharmacologic factors that should be considered in assessing candidates for kidney transplantation are presented. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  3. Traumatic brain injury pharmacological treatment: recommendations

    Directory of Open Access Journals (Sweden)

    Renato Anghinah

    Full Text Available ABSTRACT This article presents the recommendations on the pharmacological treatment employed in traumatic brain injury (TBI at the outpatient clinic of the Cognitive Rehabilitation after TBI Service of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. A systematic assessment of the consensus reached in other countries, and of articles on TBI available in the PUBMED and LILACS medical databases, was carried out. We offer recommendations of pharmacological treatments in patients after TBI with different symptoms.

  4. Pharmacological treatments for tobacco dependence

    Directory of Open Access Journals (Sweden)

    K. O. Fagerström

    2008-12-01

    Full Text Available There are currently three licensed therapies for smoking cessation: nicotine replacement (NR, bupropion and varenicline. NR can be indicated for: 1 aid in abrupt cessation; 2 gradual reduction in order to quit smoking; 3 temporary abstinence; and 4 smoking reduction maintenance. A meta-analysis has found that the relative risk of abstinence for any form of NR relative to control was 1.6. It has been found that starting NR treatment 1–3 weeks before smoking cessation and combining NR products, usually patch and gum, increases efficacy. Recently some new nicotine administration forms, i.e. lozenge, mouth spray and a pouch, have been developed. They seem to have the potential to relieve cravings faster than the current high-dose gum, and also be more preferred. Varenicline is a selective partial agonist at the 4β2 nicotinic acetylcholine receptors (nAChR. It decreases cravings and alleviates the symptoms of withdrawal. It can also reduce the rewarding and reinforcing effects of nicotine. Trials have shown varenicline to have increased efficacy relative to bupropion. Varenicline has also been compared with NR (21 mg transdermal patch in one randomised study. Abstinence at the end of treatment at 12 weeks was significantly increased for varenicline (56% compared with for nicotine patch (43%. Some post-marketing reports have expressed concern about psychiatric adverse effects, such as aggression, depression and suicides. The European Medicines Agency and the Food and Drug Administration of the USA are monitoring reported side-effects, but so far no confirmed casual relationship between these adverse effects and varenicline has been established. Bupropion inhibits neuronal re-uptake of dopamine and norepinephrine and is an antagonist on the nAChR. Its efficacy, compared with placebo, has been proved in several meta-analyses. A recent study suggests that longer pre-cessation use of bupropion, e.g. for 4 weeks, can improve efficacy results. Under

  5. Systematic variations of 87Sr/56Sr ratios, Sr compositions, selected major-oxide concentrations, and mineral abundances in piston cores from the Red Sea

    International Nuclear Information System (INIS)

    Boger, P.D.; Boger, J.L.; Faure, G.

    1980-01-01

    A mixing model is presented which relates the concentrations of Sr to the 87 Sr/ 86 Sr ratios and concentrations of other elements contained in a mixture of two components. The model is applied to the measured 87 Sr/ 86 Sr ratios, Sr, CaO, Fe 2 O 3 and SiO 2 concentrations of the detrital fractions of sediment from three piston cores representing different depositional environments in the Red Sea. The sediment is shown to be a mixture of two components derived from old sialic rocks and young volcanic rocks of the surrounding land masses. One of the cores contained a third component which is identified as authigenic Fe 2 O 3 . Removal of this contaminant is shown to return the system to its original detrital constituents. (Auth.)

  6. Pharmacologic influence on esophageal varices

    International Nuclear Information System (INIS)

    Lunderquist, A.; Owman, T.

    1983-01-01

    Selective catherization of the left gastric vein was performed after percutaneous transhepatic portography (PTP) in patients with portal hypertension and esophageal varices. Following the hypothesis that drugs increasing the lower esophageal sphincter (LES) pressure may obstruct the variceal blood flow throught the lower esophagus, the effect of different drugs (i.e., intravenous injection of vasopressin, pentagastrin, domperidone and somatostatin and subcutaneous injection of metacholine) on the variceal blood flow was examined. Vasopressin did not change the variceal blood flow; pentagastrine, with its known effect of increasing the LES pressure produced a total interruption of the flow in four of eight patients; domperiodone, also known to increase the LES pressure obstructed the variceal blood flow in the only patient examined with this drug; somatostatin has no reported action on the LES but blocked the flow in one of two patients; and metacholine, reported to increase the LES pressure did not produce any change in the flow in the three patients examined. LES pressure was recorded before and during vasopressin infusion in seven patients with portal hypertension and esophageal varices. No reaction on the pressure was found. The patient number in the study is small and the results are nonuniform but still they suggest that drugs increasing the LES tonus might be useful to control variceal blood flow. (orig.)

  7. Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens: Results from the Environment And Reproductive Health (EARTH) Study.

    Science.gov (United States)

    Nassan, Feiby L; Coull, Brent A; Gaskins, Audrey J; Williams, Michelle A; Skakkebaek, Niels E; Ford, Jennifer B; Ye, Xiaoyun; Calafat, Antonia M; Braun, Joseph M; Hauser, Russ

    2017-08-18

    Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men's exposure is understudied. We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004-2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use. Four hundred men contributed 1,037 urine samples (mean of 3/man). The largest percent increase in monoethyl phthalate (MEP) was associated with use of cologne/perfume (83%, p -value<0.01) and deodorant (74%, p -value<0.01). In contrast, the largest percent increase for parabens was associated with the use of suntan/sunblock lotion (66-156%) and hand/body lotion (79-147%). Increases in MEP and parabens were generally greater with PCP use within 6 h of urine collection. A subset of 10 PCPs that were used within 6 h of urine collection contributed to at least 70% of the weighted score and predicted a 254-1,333% increase in MEP and parabens concentrations. Associations between PCP use and concentrations of the other phthalate metabolites were not statistically significant. We identified 10 PCPs of relevance and demonstrated that their use within 6 h of urine collection strongly predicted MEP and paraben urinary concentrations. https://doi.org/10.1289/EHP1374.

  8. Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

    We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. © 2015 The British Pharmacological Society.

  9. Manufacturing cost analysis of a parabolic dish concentrator (General Electric design) for solar thermal electric power systems in selected production volumes

    Science.gov (United States)

    1981-01-01

    The manufacturing cost of a General Electric 12 meter diameter concentrator was estimated. This parabolic dish concentrator for solar thermal system was costed in annual production volumes of 100 - 1,000 - 5,000 - 10,000 - 50,000 100,000 - 400,000 and 1,000,000 units. Presented for each volume are the costs of direct labor, material, burden, tooling, capital equipment and buildings. Also presented is the direct labor personnel and factory space requirements. All costs are based on early 1981 economics.

  10. The use of monoamine pharmacological agents in the treatment of sexual dysfunction: evidence in the literature.

    Science.gov (United States)

    Moll, Jennifer L; Brown, Candace S

    2011-04-01

    The monoamine neurotransmitters serotonin, dopamine, and norepinephrine play an important role in many medical and psychological conditions, including sexual responsiveness and behavior. Pharmacological agents that modulate monoamines may help alleviate sexual dysfunction. To provide an overview of pharmacological agents that modulate monoamines and their use in the treatment of sexual dysfunction. EMBASE and PubMed search for articles published between 1950 and 2010 using key words "sexual dysfunction,"monoamines,"monoaminergic receptors," and "generic names for pharmacological agents." To assess the literature evaluating the efficacy of monoamine pharmacologic agents used in the treatment of sexual dysfunction. The literature primarily cites the use of monoaminergic agents to treat sexual side effects from serotonergic reuptake inhibitors (SSRIs), with bupropion, buspirone and ropinirole providing the most convincing evidence. Controlled trials have shown that bupropion improves overall sexual dysfunction, but not frequency of sexual activity in depressed and nondepressed patients. Nefazodone and apomorphine have been used to treat sexual dysfunction, but their use is limited by significant side effect and safety profiles. New research on pharmacologic agents with subtype selectivity at dopaminergic and serotonergic receptors and those that possess dual mechanisms of action are being investigated. There has been tremendous progress over the past 50 years in understanding the role of monoamines in sexual function and the effect of pharmacologic agents which stimulate or antagonize monoaminergic receptors on sexual dysfunction. Nevertheless, large, double-blind, placebo-controlled studies evaluating the efficacy of currently available agents in populations without comorbid disorders are limited, preventing adequate interpretation of data. Continued research on sexual function and specific receptor subtypes will result in the development of more selective

  11. Pharmacological potential of tocotrienols: a review.

    Science.gov (United States)

    Ahsan, Haseeb; Ahad, Amjid; Iqbal, Jahangir; Siddiqui, Waseem A

    2014-01-01

    Tocotrienols, members of the vitamin E family, are natural compounds found in a number of vegetable oils, wheat germ, barley, and certain types of nuts and grains. Like tocopherols, tocotrienols are also of four types viz. alpha, beta, gamma and delta. Unlike tocopherols, tocotrienols are unsaturated and possess an isoprenoid side chain. Tocopherols are lipophilic in nature and are found in association with lipoproteins, fat deposits and cellular membranes and protect the polyunsaturated fatty acids from peroxidation reactions. The unsaturated chain of tocotrienol allows an efficient penetration into tissues that have saturated fatty layers such as the brain and liver. Recent mechanistic studies indicate that other forms of vitamin E, such as γ-tocopherol, δ-tocopherol, and γ-tocotrienol, have unique antioxidant and anti-inflammatory properties that are superior to those of α-tocopherol against chronic diseases. These forms scavenge reactive nitrogen species, inhibit cyclooxygenase- and 5-lipoxygenase-catalyzed eicosanoids and suppress proinflammatory signalling, such as NF-κB and STAT. The animal and human studies show tocotrienols may be useful against inflammation-associated diseases. Many of the functions of tocotrienols are related to its antioxidant properties and its varied effects are due to it behaving as a signalling molecule. Tocotrienols exhibit biological activities that are also exhibited by tocopherols, such as neuroprotective, anti-cancer, anti-inflammatory and cholesterol lowering properties. Hence, effort has been made to compile the different functions and properties of tocotrienols in experimental model systems and humans. This article constitutes an in-depth review of the pharmacology, metabolism, toxicology and biosafety aspects of tocotrienols. Tocotrienols are detectable at appreciable levels in the plasma after supplementations. However, there is inadequate data on the plasma concentrations of tocotrienols that are sufficient to

  12. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors.

    Science.gov (United States)

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A

    2016-03-01

    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Selective mutism.

    Science.gov (United States)

    Hua, Alexandra; Major, Nili

    2016-02-01

    Selective mutism is a disorder in which an individual fails to speak in certain social situations though speaks normally in other settings. Most commonly, this disorder initially manifests when children fail to speak in school. Selective mutism results in significant social and academic impairment in those affected by it. This review will summarize the current understanding of selective mutism with regard to diagnosis, epidemiology, cause, prognosis, and treatment. Studies over the past 20 years have consistently demonstrated a strong relationship between selective mutism and anxiety, most notably social phobia. These findings have led to the recent reclassification of selective mutism as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. In addition to anxiety, several other factors have been implicated in the development of selective mutism, including communication delays and immigration/bilingualism, adding to the complexity of the disorder. In the past few years, several randomized studies have supported the efficacy of psychosocial interventions based on a graduated exposure to situations requiring verbal communication. Less data are available regarding the use of pharmacologic treatment, though there are some studies that suggest a potential benefit. Selective mutism is a disorder that typically emerges in early childhood and is currently conceptualized as an anxiety disorder. The development of selective mutism appears to result from the interplay of a variety of genetic, temperamental, environmental, and developmental factors. Although little has been published about selective mutism in the general pediatric literature, pediatric clinicians are in a position to play an important role in the early diagnosis and treatment of this debilitating condition.

  14. Indoor and outdoor concentrations of RSP, NO2 and selected volatile organic compounds at 32 shoe stalls located near busy roadways in Seoul, Korea

    International Nuclear Information System (INIS)

    Bae, Hyunjoo; Chung, Moonho; Yang, Wonho

    2004-01-01

    It is suspected that persons who work in indoor environments near busy roadways are exposed to elevated levels of air pollutants during working hours. This study evaluated the potential exposure and source contribution associated with traffic-related air pollution for workers (polishers and repairmen) in shoe stalls from each of 32 districts during working hours in Seoul, Korea. The shoe stalls have been located at very close distances to the busy roadways. In this study, shoe stall workers could be exposed to high levels of respirable suspended particulate (RSP), nitrogen dioxide (NO 2 ) and volatile organic compounds (VOCs) from outdoor sources such as traffic exhaust, as well as indoor sources in the shoe stalls such as dust on the shoes, portable gas ranges, organic solvents, adhesives and shoe polish. Compounds of particular note included indoor mean concentrations of benzene, toluene, m/p-xylene and o-xylene were 0.732, 6.777, 4.080 and 1.302 mg/m 3 , respectively, in all shoe stalls. Mean indoor/outdoor ratios for toluene and m/p-xylene concentrations were 54.52 and 20.84, respectively. The contribution of vehicle exhaust emissions to indoor air quality of shoe stalls was identified by means of correlating the relationships between simultaneously measured air pollutant concentrations indoors and outdoors. Unlike RSP and NO 2 , indoor VOCs concentrations of shoe stalls mainly originated from indoor sources vs. outdoor sources

  15. Fuzzy Clustering-Based Modeling of Surface Interactions and Emulsions of Selected Whey Protein Concentrate Combined to i-Carrageenan and Gum Arabic Solutions

    Science.gov (United States)

    Gums and proteins are valuable ingredients with a wide spectrum of applications. Surface properties (surface tension, interfacial tension, emulsion activity index “EAI” and emulsion stability index “ESI”) of 4% whey protein concentrate (WPC) in a combination with '- carrageenan (0.05%, 0.1%, and 0.5...

  16. The Effect of Selected Fruit Juice Concentrates Used as Osmotic Agents on the Drying Kinetics and Chemical Properties of Vacuum-Microwave Drying of Pumpkin

    Directory of Open Access Journals (Sweden)

    Krzysztof Lech

    2018-01-01

    Full Text Available The study examined the osmotic dehydration of pumpkin slices in chokeberry, flowering quince, and raspberry concentrated juices. Products obtained were subjected to vacuum-microwave finish drying (VMD. The objective of the study was to evaluate the drying kinetics and the chemical properties, that is, total polyphenolics content and antioxidant capacity of the vacuum-microwave-dried pumpkin products. The concentration and temperature of the juices were 40°Brix and 45°C, respectively. The pumpkin slices were pretreated in concentrated juices for 0.5, 1, 2, 3, and 6 hours. Vacuum-microwave finish drying was carried out at the power of magnetrons that ensured the maintenance of the safe temperature (below 90°C of the slices measured with the use of infrared camera. The results of the study showed that the moisture content of samples during the pretreatment in concentrated juices was decreasing until the equilibrium stage. The logarithmic model was used to describe the drying kinetics of pumpkin during VMD. Osmotic pretreatment resulted in a decrease in colour coordinates, improved the antioxidant activity of dried product, and prolonged the duration of VMD.

  17. Selective oxidation of glycerol to formic acid in highly concentrated aqueous solutions with molecular oxygen using V-substituted phosphomolybdic acids

    KAUST Repository

    Zhang, Jizhe; Sun, Miao; Han, Yu

    2014-01-01

    Formic acid is an important commodity chemical as well as a promising medium for hydrogen storage and hydrogen production. In this paper, we report that formic acid can be produced through selective oxidation of glycerol, a low-cost by-product

  18. A general method for the calculation of absolute trace gas concentrations in air and breath from selected ion flow tube mass spectrometry data

    Czech Academy of Sciences Publication Activity Database

    Španěl, Patrik; Dryahina, Kseniya; Smith, D.

    249-250, - (2006), s. 230-239 ISSN 1387-3806 R&D Projects: GA ČR GA202/03/0827 Institutional research plan: CEZ:AV0Z40400503 Keywords : selected ion flow tube * mass spectrometry * SIFT-MS * trace gas analysis Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.337, year: 2006

  19. Pharmacological therapy of chronic obstructive pulmonary disease

    African Journals Online (AJOL)

    patients with COPD require pharmacological therapy. ... pulmonary dysfunction. Clearly the patient's tolerance to the various drugs will influence the choice of long-term maintenance treatment. The other important factor in the .... blocking cervical immune responses might leave her less protected against other infections.

  20. Multidimensional Screening as a Pharmacology Laboratory Experience.

    Science.gov (United States)

    Malone, Marvin H.; And Others

    1979-01-01

    A multidimensional pharmacodynamic screening experiment that addresses drug interaction is included in the pharmacology-toxicology laboratory experience of pharmacy students at the University of the Pacific. The student handout with directions for the procedure is reproduced, drug compounds tested are listed, and laboratory evaluation results are…

  1. Radioreceptor assay: theory and applications to pharmacology

    International Nuclear Information System (INIS)

    Perret, G.; Simon, P.

    1984-01-01

    The aim of the first part of this work is to present the theory of the radioreceptor assay and to compare it to the other techniques of radioanalysis (radioimmunoassay, competitive protein binding assays). The technology of the radioreceptor assay is then presented and its components (preparation of the receptors, radioligand, incubation medium) are described. The analytical characteristics of the radioreceptor assay (specificity, sensitivity, reproductibility, accuracy) and the pharmacological significance of the results are discussed. The second part is devoted to the description of the radioreceptor assays of some pharmacological classes (neuroleptics, tricyclic antidepressants, benzodiazepines, β-blockers, anticholinergic drugs) and to their use in therapeutic drug monitoring. In conclusion, by their nature, radioreceptor assays are highly sensitive, reliable, precise, accurate and simple to perform. Their chief disadvantage relates to specificity, since any substance having an appreciable affinity to the receptor site will displace the specifically bound radioligand. Paradoxically in some cases, this lack of specificity may be advantageous in that it allows for the detection of not only the apparent compound but of active metabolites and endogenous receptor agonists as well and in that radioreceptors assays can be devised for a whole pharmacological class and not only for one drug as it is the case for classical physico-chemical techniques. For all these reasons future of radioreceptor assay in pharmacology appears promising [fr

  2. Ethnomedicinal uses and pharmacological activities of Croton ...

    African Journals Online (AJOL)

    Abstract. Purpose: To provide an overview of the ethnomedicinal uses and ... calls for detailed phytochemical and pharmacological properties of the species aimed at identifying the ... urban communities throughout its native ... sized, densely leafy tree reaching 15 m tall [17] ..... Williams College, United States; 1998; p 133.

  3. Pharmacological Interventions for Students with ADD.

    Science.gov (United States)

    Austin, Vance L.

    2003-01-01

    A review of the research on pharmacological interventions for students with attention deficit disorder finds that psychostimulants such as methylphenidate (Ritalin) are effective in improving focus and impulse control, but should be used in conjunction with psychosocial and behavioral interventions. Comprehensive medical screenings and guidelines…

  4. Jatropha Tanjorensis - Review of Phytochemistry, Pharmacology ...

    African Journals Online (AJOL)

    Based on the findings of this work, future study on the phytochemistry and chemical constituents in relation to certain other biological activities are required to fully understand the phytochemical and complex pharmacological effect of the plant specie. Further work to isolate active compounds from the plant is also necessary.

  5. Current status and challenges of cytokine pharmacology

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Anzenbacher, P.; Kmoníčková, Eva

    2009-01-01

    Roč. 157, č. 3 (2009), s. 342-361 ISSN 0007-1188 R&D Projects: GA ČR GA305/08/0535; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512 Keywords : cytokines * immunotherapy * immunopharmacology Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 5.204, year: 2009

  6. International Journal of Herbs and Pharmacological Research

    African Journals Online (AJOL)

    International Journal of Herbs and Pharmacological Research (IJHPR) [ISSN: 2315-537X; E- ISSN: 2384-6836] is a peer reviewed journal publication of Anthonio Research Center. The Journal is intended to serve as a medium for the publication of research findings in the field of Herbal medication in developing countries ...

  7. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

    Science.gov (United States)

    Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

    2017-04-01

    The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

  8. International Journal of Herbs and Pharmacological Research ...

    African Journals Online (AJOL)

    PROMOTING ACCESS TO AFRICAN RESEARCH ... International Journal of Herbs and Pharmacological Research: Advanced Search ... either term; e.g., education OR research; Use parentheses to create more complex queries; ... African Journal of Biomedical Research, African Journal of Biotechnology, African Journal of ...

  9. Pharmacological management of chronic obstructive pulmonary ...

    African Journals Online (AJOL)

    The main objective of treatment is to relieve daily symptoms, improve quality of life and importantly decrease the risk of future exacerbations. Current guidelines are based on grade A and B evidence. Pneumococcal and annual influenza vaccinations are encouraged. A holistic approach that augments pharmacological ...

  10. Emerging pharmacological therapy for functional dyspepsia.

    Science.gov (United States)

    Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Watanabe, Sumio

    2013-10-01

    Functional dyspepsia (FD) is a multifactorial disease with complex underlying pathophysiology. To date, there is no established treatment for FD. This review summarizes recent progress in pharmacological therapy for the disease. A newly developed drug, acotiamide, is expected to improve symptoms of postprandial distress syndrome. Herbal medicines are also expected to become options for FD treatment.

  11. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  12. Kinship and interaction in neuromuscular pharmacology

    NARCIS (Netherlands)

    Schiere, Sjouke

    2006-01-01

    The background of this thesis is presented in the introductory chapters and stafts with a brief history of neuromuscular relaxants. It is followed by a short description of the neuromuscular physiology and pharmacology in chapters 2 and 3, respectively. In chapter 4 the aim of the thesis is

  13. Pharmaceutical and pharmacological approaches for bioavailability

    Indian Academy of Sciences (India)

    Much research has been done to determine drug–drug and herb–drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability ...

  14. Chemical constituents, and pharmacological and toxicological ...

    African Journals Online (AJOL)

    Methods: A large number of research articles related to “Cynomorium songaricum” “pharmacological effects” .... contents in C. songaricum at different stages of its growth are varied in a .... Oral water-soluble polysaccharides of C. ... tested strains, mouse somatic cells and germ cells. .... change under the influence of heating.

  15. Pharmacological Evaluation of the Antidiarrhoeal Activity of ...

    African Journals Online (AJOL)

    This study presents the pharmacological evaluation of the effects of intraperitoneal injection of aqueous seed extract of Aframomum melegueta (AM) on diarrhoea, intestinal fluid secretion and gastrointestinal transit time, induced by castor oil in rodents. The results of the study revealed that AM (50-200 mg/kg) produced a ...

  16. Some Pharmacological Aspects of Antimalarial Drugs

    African Journals Online (AJOL)

    1974-06-15

    Jun 15, 1974 ... Some Pharmacological Aspects of Antimalarial. Drugs. D.BOTHA. SUMMARY. A short review is given of antimalarial drugs currently in use. S. Air. Med. l., 48, 1263 (1974). CLASSIFICATION. The chemotherapy of malaria may be conveniently classi- fied as (i) casual prophylaxis; (ii) suppressive treatment;.

  17. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  18. Ethnobotanical, phytochemical and pharmacological properties of ...

    African Journals Online (AJOL)

    Purpose: To present an overview of the ethnobotany, phytochemistry and pharmacology of Crinum bulbispermum so as to understand its importance and potential in primary healthcare systems. Methods: A review of the literature was undertaken and an in-depth analysis of previous research on ethnobotany, phytochemistry ...

  19. Plant cannabinoids: a neglected pharmacological treasure trove.

    Science.gov (United States)

    Mechoulam, Raphael

    2005-12-01

    Most of the cannabinoids in Cannabis sativa L. have not been fully evaluated for their pharmacological activity. A publication in this issue presents evidence that a plant cannabinoid, Delta(9)-tetrahydrocannabivarin is a potent antagonist of anandamide, a major endogenous cannabinoid. It seems possible that many of the non-psychoactive constituents of this plant will be of biological interest.

  20. Molecular Pharmacology of CXCR4 inhibition

    DEFF Research Database (Denmark)

    Steen, Anne; Rosenkilde, Mette Marie

    2012-01-01

    pharmacology of well-known CXCR4 antagonists in order to augment the potency and affinity and to increase the specificity of future CXCR4-targeting compounds. In this chapter, binding modes of CXCR4 antagonists that have been shown to mobilize stem cells are discussed. In addition, comparisons between results...

  1. Evidence-based pharmacological treatment of substance use disorders and pathological gambling

    NARCIS (Netherlands)

    van den Brink, Wim

    2012-01-01

    This review summarizes our current knowledge of the pharmacological treatment of substance use disorders and pathological gambling using data mainly from randomized controlled trials and meta-analyses regarding these randomized controlled trials. The review is restricted to the selection of first

  2. Regression models to estimate real-time concentrations of selected constituents in two tributaries to Lake Houston near Houston, Texas, 2005-07

    Science.gov (United States)

    Oden, Timothy D.; Asquith, William H.; Milburn, Matthew S.

    2009-01-01

    In December 2005, the U.S. Geological Survey in cooperation with the City of Houston, Texas, began collecting discrete water-quality samples for nutrients, total organic carbon, bacteria (total coliform and Escherichia coli), atrazine, and suspended sediment at two U.S. Geological Survey streamflow-gaging stations upstream from Lake Houston near Houston (08068500 Spring Creek near Spring, Texas, and 08070200 East Fork San Jacinto River near New Caney, Texas). The data from the discrete water-quality samples collected during 2005-07, in conjunction with monitored real-time data already being collected - physical properties (specific conductance, pH, water temperature, turbidity, and dissolved oxygen), streamflow, and rainfall - were used to develop regression models for predicting water-quality constituent concentrations for inflows to Lake Houston. Rainfall data were obtained from a rain gage monitored by Harris County Homeland Security and Emergency Management and colocated with the Spring Creek station. The leaps and bounds algorithm was used to find the best subsets of possible regression models (minimum residual sum of squares for a given number of variables). The potential explanatory or predictive variables included discharge (streamflow), specific conductance, pH, water temperature, turbidity, dissolved oxygen, rainfall, and time (to account for seasonal variations inherent in some water-quality data). The response variables at each site were nitrite plus nitrate nitrogen, total phosphorus, organic carbon, Escherichia coli, atrazine, and suspended sediment. The explanatory variables provide easily measured quantities as a means to estimate concentrations of the various constituents under investigation, with accompanying estimates of measurement uncertainty. Each regression equation can be used to estimate concentrations of a given constituent in real time. In conjunction with estimated concentrations, constituent loads were estimated by multiplying the

  3. Apomorphine and piribedil in rats: biochemical and pharmacologic studies.

    Science.gov (United States)

    Butterworth, R F; Poignant, J C; Barbeau, A

    1975-01-01

    We studied the biochemical and pharmacologic modes of action of piribedil and apomorphine in the rat. Although both drugs have many points in common, they are also different in many of their manifestations. Apomorphine causes high-intensity, short-duration stereotyped behavior; it is distributed within the brain in uneven fashion, the striatum being the area of lowest concentration as measured by fluorometry. Direct stereotactic injection within the dopaminergic mesolimbic system, and particularly the tuberculum olfactorium, produced constant intense responses. All effects of apomorphine can be blocked by pimozide, but propanolol, a beta blocker, only reduces aggression and ferocity, leaving stereotyped behaviors intact. Finally, L-5-HTP tends to reduce aggression, ferocity, and to a lesser extent stereotypy; MIF or piribedil, as well as reserpine, potentiates the stereotyped behaviors induced by apomorphine, whereas L-DOPA usually decreases them. Piribedil, on the other hand, causes low-intensity, long-duration stereotyped behavior. It is distributed within the brain almost uniformly. Most effects of piribedil can be blocked by pimozide, but propanolol blocks only aggression and ferocity, leaving stereotyped behaviors intact. On the other hand, clonidine, an alpha-receptor agonist, blocks stereotyped behaviors induced by piribedil but markedly increases aggression, ferocity, and motor activity. L-5-HTP and L-DOPA have little effect on piribedil-induced manifestations. Reserpine decreases piribedil stereotypy. The main metabolite of piribedil, S 584, had no clear-cut pharmacologic action in our hands at the dosage used. It is concluded that both apomorphine and piribedil produce stereotyped behavior by modifying the physiologic balance between mesolimbic and nigrostriatal dopaminergic systems. The other actions of apomorphine and piribedil upon aggression, ferocity, and motor activity are not always in parallel and depend probably on the fact that piribedil is less

  4. Concentrations of selected heavy metals in bryophyte tissues at Cu-mine heap Podlipa in Ľubietová (Central Slovakia)

    Science.gov (United States)

    Širka, Pavel; Midula, Pavol

    2017-04-01

    Mine heaps and wastes created by mining industry belong to one of the most extreme man-made habitat types. In addition to their specific microclimatic conditions mine heaps are also characterized by increased contents of heavy metals and toxic substances in the soil substrate. These substances are transported into plant bodies and create difficult conditions for their growth. However, there are some plants that can cope with extremely high metal contents and are capable of growing on metalliferous habitats. These plants develop unique adaptation mechanisms and basically represent modified ecotypes with specific tolerances to certain heavy metals adapted through microevolutionary processes. The toxic effects of heavy metals on vascular plants are known for quite a long time, however, bryophytes are also known to accumulate certain heavy metals without any visible signs of damage. Because of this ability they have been successfully used in biomonitoring. Chemical analysis of contaminants in samples of bryophytes can reflect the state of environmental pollution. The aim of this work was to analyze the concentrations of 6 heavy metals (Fe, Cu, Zn, Mn, Pb and Cd) in tissues of 16 bryophyte samples at an abandoned Cu deposit Podlipa in Ľubietová and to compare them with concentrations of these elemens in soil samples and 9 vascular plant species (belonging to different growth forms) in a research performed by Andráš et al. (2014) in the studied area. Bryophytes were collected at 10 sampling sites randomly chosen in the dump-field area and consist of 14 different moss species. Only above-ground parts of bryophyte thalli (separated from rhizoids, gravel, soil, needles etc.) were used for analysis. Samples were dried at room temperature and subjected to microwave mineralization (MWS - 2 Berghof). The detailed procedure is defined in the Application Report MWS - 2 / Food, Pharma, Cosmetics (Berghof). In order to determine the concentrations of studied elements, atomic

  5. Pharmacological treatment of tic disorders and Tourette Syndrome.

    Science.gov (United States)

    Roessner, Veit; Schoenefeld, Katja; Buse, Judith; Bender, Stephan; Ehrlich, Stefan; Münchau, Alexander

    2013-05-01

    The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug trials in TS patients fulfilling evidence based medicine standards are still scarce. Treatment decisions are often guided by individual needs and personal experience of treating clinicians. The present recommendations for pharmacological tic treatment are therefore based on both scientific evidence and expert opinion. As first-line treatment of tics risperidone (best evidence level for atypical antipsychotics) or tiapride (largest clinical experience in Europe and low rate of adverse reactions) are recommended. Aripiprazole (still limited but promising data with low risk for adverse reactions) and pimozide (best evidence of the typical antipsychotics) are agents of second choice. In TS patients with comorbid attention deficit hyperactivity disorder (ADHD) atomoxetine, stimulants or clonidine should be considered, or, if tics are severe, a combination of stimulants and risperidone. When mild to moderate tics are associated with obsessive-compulsive symptoms, depression or anxiety sulpiride monotherapy can be helpful. In more severe cases the combination of risperidone and a selective serotonin reuptake inhibitor should be given. In summary, further studies, particularly randomized, double-blind, placebo-controlled trials including larger and/or more homogenous patient groups over longer periods are urgently needed to enhance the scientific basis for drug treatment in tic disorders. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. [Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations].

    Science.gov (United States)

    Walczak, Katarzyna; Zmyślony, Marek

    2013-01-01

    Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers), Iran (5), China (4) and India (5). Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings). In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program.

  7. Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations

    Directory of Open Access Journals (Sweden)

    Katarzyna Walczak

    2013-04-01

    Full Text Available Background: Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Material and Methods: Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers, Iran (5, China (4 and India (5. Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. Results: We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings. In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. Conclusions: The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program. Med Pr 2013;64(2:193–198

  8. Summary of total mercury concentrations in fillets of selected sport fishes collected during 2000-2003 from Lake Natoma, Sacramento County, California

    Science.gov (United States)

    Saiki, Michael K.; Slotton, Darrell G.; May, Thomas W.; Ayers, Shaun M.; Alpers, Charles N.

    2004-01-01

    This report summarizes results of total mercury measurements in skinless fillets of sport fishes collected during August 2000, September?October 2002, and July 2003 from Lake Natoma, a small (8,760 acre-feet) afterbay for Folsom Dam on the lower American River. The primary objective of the study was to determine if mercury concentrations in fillets approached or exceeded guidelines for human consumption. The Food and Drug Administration (FDA) human-health action level for methylmercury in commercially caught fish is 1.0 ?g/g (microgram per gram); the U.S. Environmental Protection Agency (USEPA) human-health criterion for methylmercury residue in fish tissue is 0.30 ?g/g. Wet weight concentrations of total mercury in skinless fillets were as high as 0.19 ?g/g in bluegill (Lepomis macrochirus), 0.39 ?g/g in redear sunfish (L. microlophus), 1.02 ?g/g in largemouth bass (Micropterus salmoides), and 1.89 ?g/g in channel catfish (Ictalurus punctatus). Maximum concentrations of mercury in other fish species varied from 0.10 ?g/g in rainbow trout (Oncorhynchus mykiss) to 0.56 ?g/g in white catfish (A-meiurus catus). Altogether, 1 of 86 largemouth bass and 11 of 11 channel catfish exceeded the FDA human-health action level. In addition, 1 of 20 redear sunfish, 26 of 86 largemouth bass, 2 of 3 spotted bass (M. punctulatus), 1 of 1 brown bullhead (A. nebulosus), and 1 of 1 white catfish exceeded the USEPA human-health criterion. These results indicate that some fish species inhabiting Lake Natoma contain undesirably high concentrations of mercury in their skinless fillets.

  9. Mass Spectrometry-Based Metabolomics of Agave Sap (Agave salmiana after Its Inoculation with Microorganisms Isolated from Agave Sap Concentrate Selected to Enhance Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Luis M. Figueroa

    2017-11-01

    Full Text Available Saponins have been correlated with the reduction of cancer cell growth and the apoptotic effect of agave sap concentrate. Empirical observations of this artisanal Mexican food have shown that fermentation occurs after agave sap is concentrated, but little is known about the microorganisms that survive after cooking, or their effects on saponins and other metabolites. The aim of this study was to evaluate the changes in metabolites found in agave (A. salmiana sap after its fermentation with microorganisms isolated from agave sap concentrate, and demonstrate its potential use to enhance anticancer activity. Microorganisms were isolated by dilution plating and identified by 16S rRNA analysis. Isolates were used to ferment agave sap, and their corresponding butanolic extracts were compared with those that enhanced the cytotoxic activity on colon (Caco-2 and liver (Hep-G2 cancer cells. Metabolite changes were investigated by mass spectrometry-based metabolomics. Among 69 isolated microorganisms, the actinomycetes Arthrobacter globiformis and Gordonia sp. were used to analyze the metabolites, along with bioactivity changes. From the 939 ions that were mainly responsible for variation among fermented samples at 48 h, 96 h, and 192 h, four were correlated to anticancer activity. It was shown that magueyoside B, a kammogenin glycoside, was found at higher intensities in the samples fermented with Gordonia sp. that reduced Hep-G2 viability better than controls. These findings showed that microorganisms from agave sap concentrate change agave sap metabolites such as saponins. Butanolic extracts obtained after agave sap fermentation with Arthrobacter globiformis or Gordonia sp. increased the cancer cell growth inhibitory effect on colon or liver cancer cells, respectively.

  10. Variations in selected water quality variables and metal concentrations in the sediment of the lower Olifants and Selati rivers, South Africa

    Directory of Open Access Journals (Sweden)

    T. Seymore

    1994-08-01

    Full Text Available A survey of the water and sediment quality of the lower Olifants River and lower Selati River was carried out. Metal concentrations (Cr, Cu, Fe, Mn, Ni, Pb, Sr and Zn in the water and sediment, as well as the physical and chemical characteristics of the water were determined over a two-year period (April 1990 - February 1992. The water quality of the lower Selati River, which flows through the Phalaborwa area, was found to be influenced by the mining and industrial activities in the area. It was also the case with the lower Olifants River after the Selati-Olifants confluence, although the concentrations of most variables did decrease from the western side of the Kruger National Park to the eastern side due to dilution of the water by tributaries of the Olifants River. Variables of special concern were sodium, fluoride. chloride, sulphate, potassium, the total dissolved salts and the metal concentrations (except strontium. The water quality of the Selati River in the study area is a great cause of concern and a further degradation thereof cannot be afforded.

  11. Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model

    Directory of Open Access Journals (Sweden)

    Xiao Tan

    2017-02-01

    Full Text Available Persistent organic pollutants (POPs pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route, inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions (I-consistency and I I -consistency are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I-consistency results were more acceptable than the I I -consistency results.

  12. Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model.

    Science.gov (United States)

    Tan, Xiao; Gong, Zaiwu; Huang, Minji; Wang, Zhou-Jing

    2017-02-14

    Persistent organic pollutants (POPs) pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route), inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions ( I -consistency and I I -consistency) are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I -consistency results were more acceptable than the I I -consistency results.

  13. Use of selective adsorbents for adsorption and concentration of radioactive isotopes difficult measurement; Empleo de materials adsorbentes selectivos para la adsorcion y contration de isotopos radiactivos de dificil medida

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, L.; Medina, F.

    2011-07-01

    The work are focused on obtaining a selective adsorbent material to separate from the effluent of nuclear energy plants the radioactive isotopes with high average lifetimes that are in very low concentrations in order to treat them separately from the rest of waste. For this target we have worked with different materials, focusing on the utilization of the adsorptive capacity of layered double hydroxides, which can be reconstructed after being burned hosting anions in the interlayers space. (Author)

  14. Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

    Science.gov (United States)

    Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

    2018-03-01

    Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  15. Non-pharmacological measures in the pain management in newborns: nursing care

    Directory of Open Access Journals (Sweden)

    Ana Paula da Silva Morais

    2016-01-01

    Full Text Available Objective: to analyze the evidence of the literature about pain management during arterial puncture, venous and capillary in the newborn that received non-pharmacological measures before the painful procedure. Methods: this is an integrative review performed in databases. Initially, 120 articles were selected being a sample composed of ten articles. Data were collected in forms. Results: orally glucose was the most used method followed by breast milk and contact measures and the use of glucose associated or not to breast milk and contact measures. Conclusion: the use of non-pharmacological methods has been proven effective to promote the relief of pain in newborns.

  16. Development of an aflatoxin B1 specific molecularly imprinted solid phase extraction sorbent for the selective pre-concentration of toxic aflatoxin B1 from child weaning food, Tsabana

    Directory of Open Access Journals (Sweden)

    Semong Oratile

    2017-03-01

    Full Text Available This paper presents the synthesis, optimization and application of a molecularly imprinted polymer (MIP sorbent for the selective extraction and pre-concentration of the potent toxin, aflatoxin B1 (AFB1, from the child weaning food, Tsabana (manufactured in Serowe, Botswana. As a food safety regulatory measure, Tsabana must be cleared of hazardous aflatoxins, especially AFB1, before consumption. This is because AFB1 is the most common and potent of the aflatoxins commonly found in cereals. Accurate analysis of AFB1 is challenging because it exists in very low concentrations in complex, ‘dirty’ matrices such as food, making it difficult to detect using analytical instruments, even if these analytical techniques have sensitivities at the femto level. The MIP extraction sorbent synthesized in this paper deals with these challenges by selectively pre-concentrating AFB1 from real Tsabana samples, successfully achieving a pre-concentration factor of 5 and therefore significantly increasing ABF1 signal intensity for easier detection. Further advantages of this system include the short time (25.0 minutes and reasonable optimal MIP dose (20.0 mg needed for maximum AFB1 extraction by the sorbent. Scanning electron microscopy revealed that the prepared AFB1 powder particles have spherical geometries and reasonably small sizes (800 nm, two advantageous physical characteristics that are associated with excellent sorbent materials.

  17. Impaired cognition and attention in adults: pharmacological management strategies.

    Science.gov (United States)

    Allain, Hervé; Akwa, Yvette; Lacomblez, Lucette; Lieury, Alain; Bentué-Ferrer, Danièle

    2007-02-01

    Cognitive psychology has provided clinicians with specific tools for analyzing the processes of cognition (memory, language) and executive functions (attention-concentration, abstract reasoning, planning). Neuropsychology, coupled with the neurosciences (including neuroimaging techniques), has authenticated the existence of early disorders affecting the "superior or intellectual" functions of the human brain. The prevalence of cognitive and attention disorders is high in adults because all the diseases implicating the central nervous system are associated with cognitive correlates of variable intensity depending on the disease process and the age of the patient. In some pathologies, cognitive impairment can be a leading symptom such as in schizophrenia, posttraumatic stress disorder or an emblematic stigmata as in dementia including Alzheimer's disease. Paradoxically, public health authorities have only recognized as medications for improving cognitive symptoms those with proven efficacy in the symptomatic treatment of patients with Alzheimer's disease; the other cognitive impairments are relegated to the orphanage of syndromes and symptoms dispossessed of medication. The purpose of this review is to promote a true "pharmacology of cognition" based on the recent knowledge in neurosciences. Data from adult human beings, mainly concerning memory, language, and attention processes, will be reported. "Drug therapeutic strategies" for improving cognition (except for memory function) are currently rather scarce, but promising perspectives for a new neurobiological approach to cognitive pharmacology will be highlighted.

  18. delta-Opioid-induced pharmacologic myocardial hibernation during cardiopulmonary resuscitation.

    Science.gov (United States)

    Fang, Xiangshao; Tang, Wanchun; Sun, Shijie; Weil, Max Harry

    2006-12-01

    Cardiac arrest and cardiopulmonary resuscitation is an event of global myocardial ischemia and reperfusion, which is associated with severe postresuscitation myocardial dysfunction and fatal outcome. Evidence has demonstrated that mammalian hibernation is triggered by cyclic variation of a delta-opiate-like compound in endogenous serum, during which the myocardial metabolism is dramatically reduced and the myocardium tolerates the stress of ischemia and reperfusion without overt ischemic and reperfusion injury. Previous investigations also proved that the delta-opioid agonist elicited the cardioprotection in a model of regional ischemic intact heart or myocyte. Accordingly, we were prompted to search for an alternative intervention of pharmacologically induced myocardial hibernation that would result in rapid reductions of myocardial metabolism and therefore minimize the myocardial ischemic and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation. Prospective, controlled laboratory study. University-affiliated research laboratory. In the series of studies performed in the established rat and pig model of cardiac arrest and cardiopulmonary resuscitation, the delta-opioid receptor agonist, pentazocine, was administered during ventricular fibrillation. : The myocardial metabolism reflected by the concentration of lactate, or myocardial tissue PCO2 and PO2, is dramatically reduced during cardiac arrest and cardiopulmonary resuscitation. These are associated with less severe postresuscitation myocardial dysfunction and longer duration of postresuscitation survival. delta-Opioid-induced pharmacologic myocardial hibernation is an option to minimize the myocardial ischemia and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation.

  19. Pharmacology of biosimilar candidate drugs in rheumatology: a literature review.

    Science.gov (United States)

    Araújo, F; Cordeiro, I; Teixeira, F; Gonçalves, J; Fonseca, J E

    2014-01-01

    To review current evidence concerning pharmacology of biosimilar candidates to be used in rheumatology. A PubMed search up to August 2013 was performed using relevant search terms to include all studies assessing pharmacological properties of biosimilar candidates to be used in rheumatology. Data on study characteristics, type of intervention, pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence ratios was extracted. Of 280 articles screened, 5 fulfilled our inclusion criteria. Two trials, PLANETAS and PLANETRA, compared CT-P13 and infliximab in patients with active ankylosing spondylitis and rheumatoid arthritis, respectively. PK bioequivalence was demonstrated in the phase 1 PLANETAS trial by highly comparable area under the curve (AUC) and maximum drug concentrations (Cmax), whose geometric mean ratios fell between the accepted bioequivalence range of 80-125%. Equivalence in efficacy and safety was demonstrated in the phase 3 PLANETRA trial. Two phase 1 trials comparing etanercept biosimilar candidates TuNEX and HD203 in healthy volunteers showed a high degree of similarity in AUC and Cmax, with respective geometric mean ratios between PK bioequivalence range. The last included trial referred to GP2013, a rituximab biosimilar candidate, which demonstrated PK and PD bioequivalence to reference product in three different dosing regimens in cynomolgus monkeys. Infliximab, etanercept and rituximab biosimilar candidates have demonstrated PK bioequivalence in the trials included in this review. CT-P13 has recently been approved for use in the European market and the remaining biosimilar candidates are currently being tested in patients with rheumatoid arthritis.

  20. Novel kinin B1 receptor agonists with improved pharmacological profiles.

    Science.gov (United States)

    Côté, Jérôme; Savard, Martin; Bovenzi, Veronica; Bélanger, Simon; Morin, Josée; Neugebauer, Witold; Larouche, Annie; Dubuc, Céléna; Gobeil, Fernand

    2009-04-01

    There is some evidence to suggest that inducible kinin B1 receptors (B1R) may play beneficial and protecting roles in cardiovascular-related pathologies such as hypertension, diabetes, and ischemic organ diseases. Peptide B1R agonists bearing optimized pharmacological features (high potency, selectivity and stability toward proteolysis) hold promise as valuable therapeutic agents in the treatment of these diseases. In the present study, we used solid-phase methodology to synthesize a series of novel peptide analogues based on the sequence of Sar[dPhe(8)]desArg(9)-bradykinin, a relatively stable peptide agonist with moderate affinity for the human B1R. We evaluated the pharmacological properties of these peptides using (1) in vitro competitive binding experiments on recombinant human B1R and B2R (for index of selectivity determination) in transiently transfected human embryonic kidney 293 cells (HEK-293T cells), (2) ex vivo vasomotor assays on isolated human umbilical veins expressing endogenous human B1R, and (3) in vivo blood pressure tests using anesthetized lipopolysaccharide-immunostimulated rabbits. Key chemical modifications at the N-terminus, the positions 3 and 5 on Sar[dPhe(8)]desArg(9)-bradykinin led to potent analogues. For example, peptides 18 (SarLys[Hyp(3),Cha(5), dPhe(8)]desArg(9)-bradykinin) and 20 (SarLys[Hyp(3),Igl(5), dPhe(8)]desArg(9)-bradykinin) outperformed the parental molecule in terms of affinity, functional potency and duration of action in vitro and in vivo. These selective agonists should be valuable in future animal and human studies to investigate the potential benefits of B1R activation.

  1. Tourette Syndrome and comorbid ADHD: current pharmacological treatment options.

    Science.gov (United States)

    Rizzo, Renata; Gulisano, Mariangela; Calì, Paola V; Curatolo, Paolo

    2013-09-01

    Attention Deficit Hyperactivity Disorder (ADHD) is the most common co-morbid condition encountered in people with tics and Tourette Syndrome (TS). The co-occurrence of TS and ADHD is associated with a higher psychopathological, social and academic impairment and the management may represent a challenge for the clinicians. To review recent advances in management of patients with tic, Tourette Syndrome and comorbid Attention Deficit Hyperactivity Disorder. We searched peer reviewed and original medical publications (PUBMED 1990-2012) and included randomized, double-blind, controlled trials related to pharmacological treatment for tic and TS used in children and adolescents with comorbid ADHD. "Tourette Syndrome" or "Tic" and "ADHD", were cross referenced with the words "pharmacological treatment", "α-agonist", "psychostimulants", "selective norepinephrine reuptake inhibitor", "antipsychotics". Three classes of drugs are currently used in the treatment of TS and comorbid ADHD: α-agonists (clonidine and guanfacine), stimulants (amphetamine enantiomers, methylphenidate enantiomers or slow release preparation), and selective norepinephrine reuptake inhibitor (atomoxetine). It has been recently suggested that in a few selected cases partial dopamine agonists (aripiprazole) could be useful. Level A of evidence supported the use of noradrenergic agents (clonidine). Reuptake inhibitors (atomoxetine) and stimulants (methylphenidate) could be, also used for the treatment of TS and comorbid ADHD. Taking into account the risk-benefit profile, clonidine could be used as the first line treatment. However only few studies meet rigorous quality criteria in terms of study design and methodology; most trials have low statistical power due to small sample size or short duration. Treatment should be "symptom targeted" and personalized for each patient. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. A yeast expression system for functional and pharmacological studies of the malaria parasite Ca2+/H+ antiporter

    Directory of Open Access Journals (Sweden)

    Salcedo-Sora J

    2012-08-01

    Full Text Available Abstract Background Calcium (Ca2+ signalling is fundamental for host cell invasion, motility, in vivo synchronicity and sexual differentiation of the malaria parasite. Consequently, cytoplasmic free Ca2+ is tightly regulated through the co-ordinated action of primary and secondary Ca2+ transporters. Identifying selective inhibitors of Ca2+ transporters is key towards understanding their physiological role as well as having therapeutic potential, therefore screening systems to facilitate the search for potential inhibitors are a priority. Here, the methodology for the expression of a Calcium membrane transporter that can be scaled to high throughputs in yeast is presented. Methods The Plasmodium falciparum Ca2+/H+ antiporter (PfCHA was expressed in the yeast Saccharomyces cerevisiae and its activity monitored by the bioluminescence from apoaequorin triggered by divalent cations, such as calcium, magnesium and manganese. Results Bioluminescence assays demonstrated that PfCHA effectively suppressed induced cytoplasmic peaks of Ca2+, Mg2+ and Mn2+ in yeast mutants lacking the homologue yeast antiporter Vcx1p. In the scalable format of 96-well culture plates pharmacological assays with a cation antiporter inhibitor allowed the measurement of inhibition of the Ca2+ transport activity of PfCHA conveniently translated to the familiar concept of fractional inhibitory concentrations. Furthermore, the cytolocalization of this antiporter in the yeast cells showed that whilst PfCHA seems to locate to the mitochondrion of P. falciparum, in yeast PfCHA is sorted to the vacuole. This facilitates the real-time Ca2+-loading assays for further functional and pharmacological studies. Discussion The functional expression of PfCHA in S. cerevisiae and luminescence-based detection of cytoplasmic cations as presented here offer a tractable system that facilitates functional and pharmacological studies in a high-throughput format. PfCHA is shown to behave as a divalent

  3. Species-specific pharmacology of antiestrogens: role of metabolism

    International Nuclear Information System (INIS)

    Jordan, V.C.; Robinson, S.P.

    1987-01-01

    The nonsteroidal antiestrogen tamoxifen exhibits a paradoxial space species pharmacology. The drug is a full estrogen in the mouse, a partial estrogen/antiestrogen in humans and the rat, and an antiestrogen in the chick oviduct. Inasmuch as tamoxifen has antiestrogenic effects in vitro, differential metabolism of tamoxifen to estrogens might occur in the species in which it has antiestrogen pharmacology. Tamoxifen or its metabolite 4-hydroxytamoxifen could lose the alkylaminoethane side chain to form the estrogenic compound metabolite E of bisphenol. Sensitive metabolic studies with [ 3 H]tamoxifen in chicks, rats, and mice identified 4-hydroxytamoxifen as the major metabolite. Athymic mice with transplanted human breast tumors can be used to study the ability of tamoxifen to stimulate tissue or tumor growth. Estradiol caused the growth of transplanted breast cancer cells into solid tumors and a uterotrophic response. However, tamoxifen does not support tumor growth when administered alone, although it stimulates uterines growth. Since a similar profile of metabolites is sequestered in human mouse tissues, these studies strongly support the concept that the drug can selectively stimulate or inhibit events in the target tissues of different species without hometabolic intervention

  4. Biochemistry and pharmacology of rhodopsin regeneration in the vertebrate eye

    International Nuclear Information System (INIS)

    Bernstein, P.S.

    1988-01-01

    In this thesis, the missing reaction of the vertebrate visual cycle, the energy-dependent isomerization of all-trans-retinoids to 11-cis-retinoids, is investigated through biochemical and pharmacological means. The biochemical processes of vision are first probed through the use of 1,5-di-(p-aminophenoxy) pentane (DAPP), the most powerful and selective pharmacological inhibitor of dark adaptation known. Next, the biochemical pathway of isomerization of retinoids in living animals is examined through double-label radioisotope studies in normal animals and in animals treated with DAPP or other inhibitors of dark adaptation. Finally, a novel retinoid isomerase activity was discovered in homogenates of frog retina/pigment epithelium that catalyzes the endergonic isomerization of all-trans-retinoids to 11-cis-retinoids in darkness. In partially purified preparations, added [11,12- 3 H]-all-trans-retinol is converted to 11-cis-retinol and other 11-cis-retinoids, while added labeled all-trans-retinal and all-trans-retinyl palmitate are not isomerized to a significant extent

  5. Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

    Directory of Open Access Journals (Sweden)

    Dong Shang

    2017-04-01

    Full Text Available Acute pancreatitis (AP is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP.

  6. Pharmacological management of narcolepsy with and without cataplexy.

    Science.gov (United States)

    Kallweit, Ulf; Bassetti, Claudio L

    2017-06-01

    Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.

  7. Uranium concentrations in stream waters and sediments from selected sites in the eastern Seward Peninsula, Koyukuk, and Charley River areas, and across South-Central Alaska

    International Nuclear Information System (INIS)

    Sharp, R.R. Jr.; Hill, D.E.

    1978-04-01

    During the summer of 1975, a 6-week reconnaissance was conducted in widespread areas of Alaska as part of the National Uranium Resource Evaluation (NURE) program; Water, stream sediment, and bedrock samples were taken from the eastern Seward Peninsula, from north of Koyukuk River, from the Charley River area, and from across south central Alaska. This report contains the LASL uranium determinations resulting from fluorometric analysis of the water samples and delayed-neutron counting of the stream sediment samples. Results of total uranium for 611 water and 641 sediment samples, from 691 stream locations, are presented. Overlays showing the numbered sample locations and graphically portraying the concentrations of uranium in water and stream sediment samples, at 1:250,000 scale for use with existing National Topographic Map Series (NTMS) sheets and published geologic maps, are provided as plates. The main purposes of this work are to make the uranium data available to the public in the standard computer format used in the NURE Hydrogeochemical and Stream Sediment Reconnaissance (i.e., with a DOE sample number giving the latitude and longitude of each sample location) and to provide uranium concentration overlays at the standard scale of 1:250,000 adopted by the DOE for the NURE program. It also allows a plausible explanation of differences between the uranium values for sediment as determined by acid dissolution/extraction/fluorometry and by delayed-neutron counting that were noted in the earlier report

  8. Preliminary assessment of chloride concentrations, loads, and yields in selected watersheds along the Interstate 95 corridor, southeastern Connecticut, 2008-09

    Science.gov (United States)

    Brown, Craig J.; Mullaney, John R.; Morrison, Jonathan; Mondazzi, Remo

    2011-01-01

    Water-quality conditions were assessed to evaluate potential effects of road-deicer applications on stream-water quality in four watersheds along Interstate 95 (I-95) in southeastern Connecticut from November 1, 2008, through September 30, 2009. This preliminary study is part of a four-year cooperative study by the U.S. Geological Survey (USGS), the Federal Highway Administration (FHWA), and the Connecticut Department of Transportation (ConnDOT). Streamflow and water quality were studied at four watersheds?Four Mile River, Oil Mill Brook, Stony Brook, and Jordan Brook. Water-quality samples were collected and specific conductance was measured continuously at paired water-quality monitoring sites upstream and downstream from I-95. Specific conductance values were related to chloride (Cl) concentrations to assist in determining the effects of road-deicing operations on the levels of Cl in the streams. Streamflow and water-quality data were compared with weather data and with the timing, amount, and composition of deicers applied to state highways. Grab samples were collected during winter stormwater-runoff events, such as winter storms or periods of rain or warm temperatures in which melting takes place, and periodically during the spring and summer. Cl concentrations at the eight water-quality monitoring sites were well below the U.S. Environmental Protection Agency (USEPA) recommended chronic and acute Cl toxicity criteria of 230 and 860 milligrams per liter (mg/L), respectively. Specific conductance and estimated Cl concentrations in streams, particularly at sites downstream from I-95, peaked during discharge events in the winter and early spring as a result of deicers applied to roads and washed off by stormwater or meltwater. During winter storms, deicing activities, or subsequent periods of melting, specific conductance and estimated Cl concentrations peaked as high as 703 microsiemens per centimeter (?S/cm) and 160 mg/L at the downstream sites. During most of

  9. The influence of physical exercise on alterations in concentrations of neuropeptide Y, leptin and other selected hormonal and metabolic parameters in sportspeople

    Directory of Open Access Journals (Sweden)

    B Zajadacz

    2009-12-01

    Full Text Available The aim of this study was to evaluate the behaviour and relationships between hormones, and metabolic blood parameters essential for energetic balance control during rest, exercise and restitution. Two groups of young boys (17 cyclists and 11 canoeists were tested twice. Tests were performed on a cycloergometer. During the first study, anaerobic threshold was determined by a non-invasive method and in the second one - cyclists performed prolonged 2-hour exercise below anaerobic threshold and canoeists - 20-min effort above anaerobic threshold. Neuropeptide Y (NPY, leptin, insulin, C-peptide, metabolic clearance of insulin, growth hormone (GH, somatomedin C (IGF1 and glycaemia were analysed. Values of NPY and GH measured directly after exercise were significantly higher than the values of these parameters at rest, in both groups. However, effort did not cause significant changes in leptin concentration and insulin clearance in both groups. Besides, it was shown that 20-min exercise had no influence on insulin concentration in canoeists blood. In these studies significantly lower IGF1 value during restitution than directly after exercise was also noted in the cyclists group. Relations between measured hormonal parameters indicate that some mechanisms, which supply the organism with necessary energetic substrates during the effort, and accelerate the restitution are activated.

  10. Pharmacists' and general practitioners' pharmacology knowledge and pharmacotherapy skills

    NARCIS (Netherlands)

    Keijsers, Carolina J P W; Leendertse, Anne J; Faber, Adrianne; Brouwers, Jacobus R B J; de Wildt, Dick J; Jansen, Paul A F

    Understanding differences in the pharmacology knowledge and pharmacotherapy skills of pharmacists and physicians is vital to optimizing interprofessional collaboration and education. This study investigated these differences and the potential influence of work experience. The pharmacology knowledge

  11. Water quality of storm runoff and comparison of procedures for estimating storm-runoff loads, volume, event-mean concentrations, and the mean load for a storm for selected properties and constituents for Colorado Springs, southeastern Colorado, 1992

    Science.gov (United States)

    Von Guerard, Paul; Weiss, W.B.

    1995-01-01

    The U.S. Environmental Protection Agency requires that municipalities that have a population of 100,000 or greater obtain National Pollutant Discharge Elimination System permits to characterize the quality of their storm runoff. In 1992, the U.S. Geological Survey, in cooperation with the Colorado Springs City Engineering Division, began a study to characterize the water quality of storm runoff and to evaluate procedures for the estimation of storm-runoff loads, volume and event-mean concentrations for selected properties and constituents. Precipitation, streamflow, and water-quality data were collected during 1992 at five sites in Colorado Springs. Thirty-five samples were collected, seven at each of the five sites. At each site, three samples were collected for permitting purposes; two of the samples were collected during rainfall runoff, and one sample was collected during snowmelt runoff. Four additional samples were collected at each site to obtain a large enough sample size to estimate storm-runoff loads, volume, and event-mean concentrations for selected properties and constituents using linear-regression procedures developed using data from the Nationwide Urban Runoff Program (NURP). Storm-water samples were analyzed for as many as 186 properties and constituents. The constituents measured include total-recoverable metals, vola-tile-organic compounds, acid-base/neutral organic compounds, and pesticides. Storm runoff sampled had large concentrations of chemical oxygen demand and 5-day biochemical oxygen demand. Chemical oxygen demand ranged from 100 to 830 milligrams per liter, and 5.-day biochemical oxygen demand ranged from 14 to 260 milligrams per liter. Total-organic carbon concentrations ranged from 18 to 240 milligrams per liter. The total-recoverable metals lead and zinc had the largest concentrations of the total-recoverable metals analyzed. Concentrations of lead ranged from 23 to 350 micrograms per liter, and concentrations of zinc ranged from 110

  12. Pharmacologic Treatments for Binge-Eating Disorder.

    Science.gov (United States)

    McElroy, Susan L

    2017-01-01

    Binge-eating disorder (BED) is the most common eating disorder and is associated with poor physical and mental health outcomes. Psychological and behavioral interventions have been a mainstay of treatment for BED, but as understanding of this disorder has grown, pharmacologic agents have become promising treatment options for some patients. At this time, only one drug-the stimulant prodrug lisdexamfetamine-is approved for the treatment of BED. Numerous classes of medications including antidepressants, anticonvulsants, and antiobesity drugs have been explored as off-label treatments for BED with variable success. Although not all patients with BED may be suitable candidates for pharmacotherapy, all patients should be considered for and educated about pharmacologic treatment options. © Copyright 2017 Physicians Postgraduate Press, Inc.

  13. Pharmacology profiling of chemicals and proteins

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl

    between pharmaceuticals and proteins in vivo potential leads to unwanted adverse effects, toxicity and reduced half-life, but can also lead to novel therapeutic effects of already approved pharmaceuticals. Hence identification of in vivo targets is of importance in discovery, development and repurposing....... This limitation complicates adverse effect assessment in the early drug-development phase, thus contributing to drugattrition. Prediction models offer the possibility to close these gaps and provide more complete pharmacology profiles, however improvements in performances are required for these tools to serve...... to its nonself origin, which potentially alters the pharmacology profile of the substance. The neutralization of biopharmaceuticals by antidrug antibodies (ADAs) is an important element in the immune response cascade, however studies of ADA binding site on biopharmaceuticals, referred to as B...

  14. Common mullein, pharmacological and chemical aspects

    Directory of Open Access Journals (Sweden)

    Muhammad Riaz

    Full Text Available Verbascum thapsus L. [Khardhag or Common mullein], a member of the family Scrophulariaceae, is a famous herb that is found all over Europe, in temperate Asia, in North America and is well-reputed due to its medicinal properties. This medicinal herb contains various chemical constituents like saponins, iridoid and phenylethanoid glycosides, flavonoids, vitamin C and minerals. It is famous in various communities worldwide for the treatment of various disorders of both humans and animals aliments. A number of pharmacological activities such as anti-inflammatory, antioxidant, anticancer, antimicrobial, antiviral, antihepatotoxic and anti-hyperlipidemic activity have been ascribed to this plant. The plant is used to treat tuberculosis also, earache and bronchitis. In the present paper botanical and ethnomedicinal description, pharmacological profile and phytochemistry of this herb is being discussed.

  15. Pharmacologic management of chronic neuropathic pain

    Science.gov (United States)

    Mu, Alex; Weinberg, Erica; Moulin, Dwight E.; Clarke, Hance

    2017-01-01

    Abstract Objective To provide family physicians with a practical clinical summary of the Canadian Pain Society (CPS) revised consensus statement on the pharmacologic management of neuropathic pain. Quality of evidence A multidisciplinary interest group within the CPS conducted a systematic review of the literature on the current treatments of neuropathic pain in drafting the revised consensus statement. Main message Gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are the first-line agents for treating neuropathic pain. Tramadol and other opioids are recommended as second-line agents, while cannabinoids are newly recommended as third-line agents. Other anticonvulsants, methadone, tapentadol, topical lidocaine, and botulinum toxin are recommended as fourth-line agents. Conclusion Many pharmacologic analgesics exist for the treatment of neuropathic pain. Through evidence-based recommendations, the CPS revised consensus statement helps guide family physicians in the management of patients with neuropathic pain. PMID:29138154

  16. Pharmacological evaluation of bee venom and melittin

    Directory of Open Access Journals (Sweden)

    Camila G. Dantas

    Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

  17. Concentrated Ownership

    DEFF Research Database (Denmark)

    Rose, Caspar

    2014-01-01

    This entry summarizes the main theoretical contributions and empirical findings in relation to concentrated ownership from a law and economics perspective. The various forms of concentrated ownership are described as well as analyzed from the perspective of the legal protection of investors......, especially minority shareholders. Concentrated ownership is associated with benefits and costs. Concentrated ownership may reduce agency costs by increased monitoring of top management. However, concentrated ownership may also provide dominating owners with private benefits of control....

  18. Local Anesthetics: Review of Pharmacological Considerations

    Science.gov (United States)

    Becker, Daniel E; Reed, Kenneth L

    2012-01-01

    Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article. PMID:22822998

  19. Conception of pharmacological knowledge and needs amongst ...

    African Journals Online (AJOL)

    Students who are taking/have taken the medical pharmacology course completed an 18-question survey within 10min by marking one/more choices from ... and 31.1% different drugs in a group; 45.8% prefer to study lecturers' notes, 26.7% textbooks, 9.8% the Internet, and 2.7% journals; 46.7% use standard textbooks, ...

  20. Electronic cigarettes and nicotine clinical pharmacology

    OpenAIRE

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abst...

  1. Pharmacological interventions to treat phlebitis: systematic review.

    Science.gov (United States)

    dos Reis, Paula Elaine Diniz; Silveira, Renata Cristina de Campos Pereira; Vasques, Christiane Inocêncio; de Carvalho, Emilia Campos

    2009-01-01

    This study presents a systematic review for evaluating effective pharmacological actions for the treatment of phlebitis stemming from infusion therapy. The studies reviewed were categorized according to the type of therapeutic approach proposed by the author and by the level of evidence presented. The review found that topical nitroglycerin and notoginseny were more effective in the reduction of the inflammatory process when compared with other proposed alternatives. Nevertheless, the development of research related to possible alternatives for the treatment of phlebitis is important.

  2. Pharmacological Aspects of Neuro-Immune Interactions.

    Science.gov (United States)

    Tarasov, Vadim V; Kudryashov, Nikita V; Chubarev, Vladimir N; Kalinina, Tatiana S; Barreto, George E; Ashraf, Ghulam Md; Aliev, Gjumrakch

    2018-01-01

    The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacological effects of psychotropic drugs possessing immunomodulatory and/or antiviral properties have shown a correlation between central effects of examined drugs associated with the impact on the processes of neurogenesis of adult brain and survival of neurons, and their ability to alter levels of key proinflammatory cytokines. The changes that occur as a result of the influence of pharmacological agents at one of the systems should inevitably lead to the functional reorganization at another. Integrative mechanisms underlying the neuro-immune interactions may explain the "pleiotropic" pharmacological effects of some antiviral and immunomodulatory drugs. Amantadine, which was originally considered as an antiviral agent, was approved as anti-parkinsonic drug after its wide medical use. The prolonged administration of interferon alpha caused depression in 30-45% of patients, thus limiting its clinical use. The antiviral drug "Oseltamivir" may provoke the development of central side effects, including abnormal behavior, delirium, impaired perception and suicides. Anti-herpethetical drug "Panavir" shows pronounced neuroprotective properties. The purpose of this review is to analyze the experimental and clinical data related to central effects of drugs with antiviral or/and immunotropic activity, and to discover the relationship of these effects with changes in reactivity of immune system and proinflammatory response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Concentrations of selected metals in Quaternary-age fluvial deposits along the lower Cheyenne and middle Belle Fourche Rivers, western South Dakota, 2009-10

    Science.gov (United States)

    Stamm, John F.; Hoogestraat, Galen K.

    2012-01-01

    potentially be inundated during high-flow events. Sampling began in 2009 and was completed in 2010. A total of 74 geochemical samples were collected from fluvial deposits at reference sites, and 473 samples were collected from potentially contaminated sites. Sediment samples collected were analyzed for 23 metals, including arsenic and mercury. Sequential replicate, split duplicate, and field quality-control samples were analyzed for quality assurance of data-collection methods. The metal concentrations in sediment samples and location information are presented in this report in electronic format (Microsoft Excel), along with non-parametric summary statistics of those data. Cross-sectional topography is graphed with arsenic and mercury concentrations on transects at the potentially contaminated sites. The mean arsenic concentration in reference sediment samples was 8 milligrams per kilogram (mg/kg), compared to 250, 650, and 76 mg/kg for potentially contaminated sediment samples at the surface of the middle Belle Fourche River site, the subsurface of the middle Belle Fourche River site, and the surface of the lower Cheyenne River site, respectively. The mean mercury concentration in reference sediment samples was 16 micrograms per kilogram (μg/kg), compared to 130, 370, and 71 μg/kg for potentially contaminated sediment samples at the surface of the middle Belle Fourche River site, the subsurface of the middle Belle Fourche River site, and the surface of the lower Cheyenne River site, respectively.

  4. Effects of biochar and alkaline amendments on cadmium immobilization, selected nutrient and cadmium concentrations of lettuce (Lactuca sativa) in two contrasting soils

    DEFF Research Database (Denmark)

    Woldetsadik, Desta; Drechsel, Pay; Keraita, Bernard

    2016-01-01

    To assess the efficiency of seven treatments including biochars produced from dried faecal matter and manures as stabilizing agents of cadmium (Cd)-spiked soils, lettuce was grown in glasshouse on two contrasting soils. The soils used were moderately fertile silty loam and less fertile sandy loam...... and the applied treatments were 7 % w/w. The reduction of bioavailable Cd (ammonium nitrate extractable) and its phytoavailability for lettuce were used as assessment criteria in the evaluation of stabilization performance of each treatment. Moreover, the agronomic values of the treatments were also investigated...... extracts. The immobilization potential of faecal matter biochar and lime were superior than the other treatments. However, lime and egg shell promoted statistically lower yield and P, K and Zn concentrations response of lettuce plants compared to the biochar treatments. The lowest Cd and highest P tissue...

  5. Solid/liquid partition coefficients (K{sub d}) and plant/soil concentration ratios (CR) for selected soils, tills and sediments at Forsmark

    Energy Technology Data Exchange (ETDEWEB)

    Sheppard, Steve (ECOMatters Inc. (Canada)); Sohlenius, Gustav (Sveriges geologiska undersoekning (Sweden)); Omberg, Lars-Gunnar (ALS Scandinavia AB (Sweden)); Borgiel, Mikael (Sveriges Vattenekologer AB (Sweden)); Grolander, Sara (Facilia AB (Sweden)); Norden, Sara (Svensk Kaernbraenslehantering AB (Sweden))

    2011-11-15

    Solid/liquid partition coefficients (K{sub d}) are used to indicate the relative mobility of radionuclides and elements of concern from nuclear fuel waste, as well as from other sources. To indicate the uptake of radionuclides in biota concentration ratios (CR) between soil and biota are used. This report summarized K{sub d} data for regolith and marine sediments based on concentrations of 69 indigenous stable elements measured from samples collected at the Forsmark site and CR data concerning cereals growing on these soils. The samples included 50 regolith samples from agricultural land and wetlands, 8 samples of till collected at different depths, and two marine sediment samples. In addition, cereal grains, stems and roots were collected from 4 sites for calculation of CRs. The regolith samples represented the major 5 deposits, which can be used as arable land, at the site (clayey till, glacial clay, clay gyttja and peat (cultivated and undisturbed)). K{sub d} values were generally lower for peat compared to clay soils. There were also clear differences in K{sub d} resulting from differences in soil chemistry within each regolith type. Soil pH was the most important factor, and K{sub d} values for many elements were lower in acidic clay soils compared to basic clay soils. Although there were only a few samples of sandy till and marine sediment, the K{sub d} values were generally consistent with the corresponding regolith K{sub d} values. Of the different cereal parts the grain always had the lowest CR. In most cases, the root CR was significantly higher than the grain CR, whereas only for a few elements were the grain and stem CR values different

  6. Solid/liquid partition coefficients (Kd) and plant/soil concentration ratios (CR) for selected soils, tills and sediments at Forsmark

    International Nuclear Information System (INIS)

    Sheppard, Steve; Sohlenius, Gustav; Omberg, Lars-Gunnar; Borgiel, Mikael; Grolander, Sara; Norden, Sara

    2011-11-01

    Solid/liquid partition coefficients (K d ) are used to indicate the relative mobility of radionuclides and elements of concern from nuclear fuel waste, as well as from other sources. To indicate the uptake of radionuclides in biota concentration ratios (CR) between soil and biota are used. This report summarized K d data for regolith and marine sediments based on concentrations of 69 indigenous stable elements measured from samples collected at the Forsmark site and CR data concerning cereals growing on these soils. The samples included 50 regolith samples from agricultural land and wetlands, 8 samples of till collected at different depths, and two marine sediment samples. In addition, cereal grains, stems and roots were collected from 4 sites for calculation of CRs. The regolith samples represented the major 5 deposits, which can be used as arable land, at the site (clayey till, glacial clay, clay gyttja and peat (cultivated and undisturbed)). K d values were generally lower for peat compared to clay soils. There were also clear differences in K d resulting from differences in soil chemistry within each regolith type. Soil pH was the most important factor, and K d values for many elements were lower in acidic clay soils compared to basic clay soils. Although there were only a few samples of sandy till and marine sediment, the K d values were generally consistent with the corresponding regolith K d values. Of the different cereal parts the grain always had the lowest CR. In most cases, the root CR was significantly higher than the grain CR, whereas only for a few elements were the grain and stem CR values different

  7. Mutation of the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia.

    Science.gov (United States)

    Kemter, Elisabeth; Rathkolb, Birgit; Bankir, Lise; Schrewe, Anja; Hans, Wolfgang; Landbrecht, Christina; Klaften, Matthias; Ivandic, Boris; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabé de Angelis, Martin; Wolf, Eckhard; Wanke, Ruediger; Aigner, Bernhard

    2010-06-01

    The bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter NKCC2, located in the thick ascending limb of Henle's loop, plays a critical role in the kidney's ability to concentrate urine. In humans, loss-of-function mutations of the solute carrier family 12 member 1 gene (SLC12A1), coding for NKCC2, cause type I Bartter syndrome, which is characterized by prenatal onset of a severe polyuria, salt-wasting tubulopathy, and hyperreninemia. In this study, we describe a novel chemically induced, recessive mutant mouse line termed Slc12a1(I299F) exhibiting late-onset manifestation of type I Bartter syndrome. Homozygous mutant mice are viable and exhibit severe polyuria, metabolic alkalosis, marked increase in plasma urea but close to normal creatininemia, hypermagnesemia, hyperprostaglandinuria, hypotension,, and osteopenia. Fractional excretion of urea is markedly decreased. In addition, calcium and magnesium excretions are more than doubled compared with wild-type mice, while uric acid excretion is twofold lower. In contrast to hyperreninemia present in human disease, plasma renin concentration in homozygotes is not increased. The polyuria observed in homozygotes may be due to the combination of two additive factors, a decrease in activity of mutant NKCC2 and an increase in medullary blood flow, due to prostaglandin-induced vasodilation, that impairs countercurrent exchange of urea in the medulla. In conclusion, this novel viable mouse line with a missense Slc12a1 mutation exhibits most of the features of type I Bartter syndrome and may represent a new model for the study of this human disease.

  8. Phage Therapy: Eco-Physiological Pharmacology

    Directory of Open Access Journals (Sweden)

    Stephen T. Abedon

    2014-01-01

    Full Text Available Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies, impact on body-associated microbiota (as ecological communities, and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.

  9. Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

    Directory of Open Access Journals (Sweden)

    Frederickson Martyn

    2010-01-01

    Full Text Available Abstract Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal

  10. Pharmacological Profile of Nociceptin/Orphanin FQ Receptors Interacting with G-Proteins and β-Arrestins 2.

    Directory of Open Access Journals (Sweden)

    D Malfacini

    Full Text Available Nociceptin/orphanin FQ (N/OFQ controls several biological functions by selectively activating an opioid like receptor named N/OFQ peptide receptor (NOP. Biased agonism is emerging as an important and therapeutically relevant pharmacological concept in the field of G protein coupled receptors including opioids. To evaluate the relevance of this phenomenon in the NOP receptor, we used a bioluminescence resonance energy transfer technology to measure the interactions of the NOP receptor with either G proteins or β-arrestin 2 in the absence and in presence of increasing concentration of ligands. A large panel of receptor ligands was investigated by comparing their ability to promote or block NOP/G protein and NOP/arrestin interactions. In this study we report a systematic analysis of the functional selectivity of NOP receptor ligands. NOP/G protein interactions (investigated in cell membranes allowed a precise estimation of both ligand potency and efficacy yielding data highly consistent with the known pharmacological profile of this receptor. The same panel of ligands displayed marked differences in the ability to promote NOP/β-arrestin 2 interactions (evaluated in whole cells. In particular, full agonists displayed a general lower potency and for some ligands an inverted rank order of potency was noted. Most partial agonists behaved as pure competitive antagonists of receptor/arrestin interaction. Antagonists displayed similar values of potency for NOP/Gβ1 or NOP/β-arrestin 2 interaction. Using N/OFQ as reference ligand we computed the bias factors of NOP ligands and a number of agonists with greater efficacy at G protein coupling were identified.

  11. Differences in pharmacology of tumor necrosis factor (TNF antagonists

    Directory of Open Access Journals (Sweden)

    S. Bombardieri

    2011-09-01

    Full Text Available The commercially available inhibitors of TNF are constituted by two classes of molecules: the soluble receptors (Etanercept: Amgen Inc. Wyeth and the monoclonal antibodies (Adalimumab: Abbott Laboratories and Infliximab: Centocor, Inc.. The differences in their molecular structure, mechanism of action, pharmacokinetics (PK and pharmacodynamics (PD are discussed, along with the differences concerning dose, administration regimens, drug concentrations and pharmacological interactions. In order to explain the clinical differences observed when these agents are used in the “real world”, which can arise from the respective PK characteristics (kinetics, route and frequency of administration, type of TNF binding, effects on cytokines and PD responses and peculiar mechanisms of action, with distinctive immune function (LFTa inactivation; apoptosis induction, TNF immunoprecipitation, C1q binding and CDC induction; Fcg cross-linking and ADCC induction, the dynamics of interaction of the two classes of neutralizing molecules with TNF, and the ability in restoring TNF homeostasis, are outlined.

  12. Suspended-sediment concentrations, loads, total suspended solids, turbidity, and particle-size fractions for selected rivers in Minnesota, 2007 through 2011

    Science.gov (United States)

    Ellison, Christopher A.; Savage, Brett E.; Johnson, Gregory D.

    2014-01-01

    Sediment-laden rivers and streams pose substantial environmental and economic challenges. Excessive sediment transport in rivers causes problems for flood control, soil conservation, irrigation, aquatic health, and navigation, and transports harmful contaminants like organic chemicals and eutrophication-causing nutrients. In Minnesota, more than 5,800 miles of streams are identified as impaired by the Minnesota Pollution Control Agency (MPCA) due to elevated levels of suspended sediment. The U.S. Geological Survey, in cooperation with the MPCA, established a sediment monitoring network in 2007 and began systematic sampling of suspended-sediment concentrations (SSC), total suspended solids (TSS), and turbidity in rivers across Minnesota to improve the understanding of fluvial sediment transport relations. Suspended-sediment samples collected from 14 sites from 2007 through 2011 indicated that the Zumbro River at Kellogg in the driftless region of southeast Minnesota had the highest mean SSC of 226 milligrams per liter (mg/L) followed by the Minnesota River at Mankato with a mean SSC of 193 mg/L. During the 2011 spring runoff, the single highest SSC of 1,250 mg/L was measured at the Zumbro River. The lowest mean SSC of 21 mg/L was measured at Rice Creek in the northern Minneapolis- St. Paul metropolitan area. Total suspended solids (TSS) have been used as a measure of fluvial sediment by the MPCA since the early 1970s; however, TSS concentrations have been determined to underrepresent the amount of suspended sediment. Because of this, the MPCA was interested in quantifying the differences between SSC and TSS in different parts of the State. Comparisons between concurrently sampled SSC and TSS indicated significant differences at every site, with SSC on average two times larger than TSS concentrations. The largest percent difference between SSC and TSS was measured at the South Branch Buffalo River at Sabin, and the smallest difference was observed at the Des Moines

  13. Pharmacologic management of neuropathic pain: Evidence-based recommendations

    DEFF Research Database (Denmark)

    Dworkin, Robert H.; O'Connor, Alec B.; Backonja, Miroslav

    2007-01-01

    Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered...... and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second......, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs...

  14. Pharmacological enhancement of treatment for amblyopia

    Directory of Open Access Journals (Sweden)

    Rashad MA

    2012-03-01

    Full Text Available Mohammad A RashadOphthalmology Department, Faculty of Medicine, Ain Shams University, Cairo, EgyptBackground: The purpose of this study was to compare a weight-adjusted dose of carbidopa-levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia.Methods: This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks.Results: The mean logarithm of the minimal angle of resolution (logMAR of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51 than in the pharmacological enhancement group (0.58, 0.49, and 0.56 at three follow-up visits (at months 1, 3, and 12, respectively. There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51 and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56 at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively. The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5% than in the occlusion group (30%. The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3% than in the occlusion group (22%.Conclusion: Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add

  15. Pharmacological enhancement of treatment for amblyopia

    Science.gov (United States)

    Rashad, Mohammad A

    2012-01-01

    Background The purpose of this study was to compare a weight-adjusted dose of carbidopa- levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia. Methods This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks. Results The mean logarithm of the minimal angle of resolution (logMAR) of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51) than in the pharmacological enhancement group (0.58, 0.49, and 0.56) at three follow-up visits (at months 1, 3, and 12, respectively). There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51) and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56) at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively). The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5%) than in the occlusion group (30%). The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3%) than in the occlusion group (22%). Conclusion Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add to the effect of occlusion in severe amblyopia and bilateral amblyopia. PMID:22536029

  16. Pharmacology of ayahuasca administered in two repeated doses.

    Science.gov (United States)

    Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

    2012-02-01

    Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

  17. Elliptical concentrators.

    Science.gov (United States)

    Garcia-Botella, Angel; Fernandez-Balbuena, Antonio Alvarez; Bernabeu, Eusebio

    2006-10-10

    Nonimaging optics is a field devoted to the design of optical components for applications such as solar concentration or illumination. In this field, many different techniques have been used to produce optical devices, including the use of reflective and refractive components or inverse engineering techniques. However, many of these optical components are based on translational symmetries, rotational symmetries, or free-form surfaces. We study a new family of nonimaging concentrators called elliptical concentrators. This new family of concentrators provides new capabilities and can have different configurations, either homofocal or nonhomofocal. Translational and rotational concentrators can be considered as particular cases of elliptical concentrators.

  18. Chemistry of Selected Core Samples, Concentrate, Tailings, and Tailings Pond Waters: Pea Ridge Iron (-Lanthanide-Gold) Deposit, Washington County, Missouri

    Science.gov (United States)

    Grauch, Richard I.; Verplanck, Philip L.; Seeger, Cheryl M.; Budahn, James R.; Van Gosen, Bradley S.

    2010-01-01

    The Minerals at Risk and for Emerging Technologies Project of the U.S. Geological Survey (USGS) Mineral Resources Program is examining potential sources of lanthanide elements (rare earth elements) as part of its objective to provide up-to-date geologic information regarding mineral commodities likely to have increased demand in the near term. As part of the examination effort, a short visit was made to the Pea Ridge iron (-lanthanide-gold) deposit, Washington County, Missouri in October 2008. The deposit, currently owned by Wings Enterprises, Inc. of St. Louis, Missouri (Wings), contains concentrations of lanthanides that may be economic as a primary product or as a byproduct of iron ore production. This report tabulates the results of chemical analyses of the Pea Ridge samples and compares rare earth elements contents for world class lanthanide deposits with those of the Pea Ridge deposit. The data presented for the Pea Ridge deposit are preliminary and include some company data that have not been verified by the USGS or by the Missouri Department of Natural Resources, Division of Geology and Land Survey (DGLS), Geological Survey Program (MGS). The inclusion of company data is for comparative purposes only and does not imply an endorsement by either the USGS or MGS.

  19. Some selected heavy metal concentrations in water, sediment, and oysters in the Er-Ren estuary, Taiwan: chemical fractions and the implications for biomonitoring.

    Science.gov (United States)

    Chen, Yueh-Min; Li, Hong-Chun; Tsao, Tsung-Ming; Wang, Liaug-Chi; Chang, Yin

    2014-11-01

    Studies of heavy metal contamination and ecological risk in estuaries are an important emerging area of environmental science. However, there have been few detailed studies of heavy metal contamination that concern the spatial variation of heavy metal levels in water, sediment, and oyster tissue. Because of the effective uptake of heavy metals, cultured oysters are a cheap and effective subject for study. This study, conducts an experiment in the Er-Ren river to examine the biological uptake of heavy metals in farmed, cultured oysters. The distribution of copper, zinc, lead, cadmium, and arsenic concentrations in water, sediment, and oysters from the Er-Ren river is also evaluated. By sequential extraction of the sediments, the following order of mobilities is found for heavy metals Pb > Cd > As > Zn > Cu. The highest percentages of heavy metals are found in the residual phase. The mean uptake rates for young oysters are 7.24 mg kg(-1) day(-1) for Cu and 94.52 mg kg(-1) day(-1) for Zn, but that for adult oyster is 10.79 mg kg(-1) day(-1) for Cu and 137.24 mg kg(-1) day(-1) for Zn. With good policies and management, the establishment of cultured oyster frames in these contaminated tributaries and near shore environments is a potential method for removing Cu and Zn and protecting the coast.

  20. Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review

    Science.gov (United States)

    Merlin, Jessica S.; Bulls, Hailey W.; Vucovich, Lee A.; Edelman, E. Jennifer; Starrels, Joanna L.

    2016-01-01

    Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients’ chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non-pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (≤12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research. PMID:27267445

  1. Pharmacology Goes Concept-Based: Course Design, Implementation, and Evaluation.

    Science.gov (United States)

    Lanz, Amelia; Davis, Rebecca G

    Although concept-based curricula are frequently discussed in the nursing education literature, little information exists to guide the development of a concept-based pharmacology course. Traditionally, nursing pharmacology courses are taught with an emphasis on drug class where a prototype drug serves as an exemplar. When transitioning pharmacology to a concept-based course, special considerations are in order. How can educators successfully integrate essential pharmacological content into a curriculum structured around nursing concepts? This article presents one approach to the design and implementation of a concept-based undergraduate pharmacology course. Planning methods, supportive teaching strategies, and course evaluation procedures are discussed.

  2. Concentration risk

    Directory of Open Access Journals (Sweden)

    Matić Vesna

    2016-01-01

    Full Text Available Concentration risk has been gaining a special dimension in the contemporary financial and economic environment. Financial institutions are exposed to this risk mainly in the field of lending, mostly through their credit activities and concentration of credit portfolios. This refers to the concentration of different exposures within a single risk category (credit risk, market risk, operational risk, liquidity risk.

  3. Interprofessional education in pharmacology using high-fidelity simulation.

    Science.gov (United States)

    Meyer, Brittney A; Seefeldt, Teresa M; Ngorsuraches, Surachat; Hendrickx, Lori D; Lubeck, Paula M; Farver, Debra K; Heins, Jodi R

    2017-11-01

    This study examined the feasibility of an interprofessional high-fidelity pharmacology simulation and its impact on pharmacy and nursing students' perceptions of interprofessionalism and pharmacology knowledge. Pharmacy and nursing students participated in a pharmacology simulation using a high-fidelity patient simulator. Faculty-facilitated debriefing included discussion of the case and collaboration. To determine the impact of the activity on students' perceptions of interprofessionalism and their ability to apply pharmacology knowledge, surveys were administered to students before and after the simulation. Attitudes Toward Health Care Teams scale (ATHCT) scores improved from 4.55 to 4.72 on a scale of 1-6 (p = 0.005). Almost all (over 90%) of the students stated their pharmacology knowledge and their ability to apply that knowledge improved following the simulation. A simulation in pharmacology is feasible and favorably affected students' interprofessionalism and pharmacology knowledge perceptions. Pharmacology is a core science course required by multiple health professions in early program curricula, making it favorable for incorporation of interprofessional learning experiences. However, reports of high-fidelity interprofessional simulation in pharmacology courses are limited. This manuscript contributes to the literature in the field of interprofessional education by demonstrating that an interprofessional simulation in pharmacology is feasible and can favorably affect students' perceptions of interprofessionalism. This manuscript provides an example of a pharmacology interprofessional simulation that faculty in other programs can use to build similar educational activities. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Concentrator Photovoltaics

    CERN Document Server

    Luque, Antonio L

    2007-01-01

    Photovoltaic solar-energy conversion is one of the most promising technologies for generating renewable energy, and conversion of concentrated sunlight can lead to reduced cost for solar electricity. In fact, photovoltaic conversion of concentrated sunlight insures an efficient and cost-effective sustainable power resource. This book gives an overview of all components, e.g. cells, concentrators, modules and systems, for systems of concentrator photovoltaics. The authors report on significant results related to design, technology, and applications, and also cover the fundamental physics and market considerations. Specific contributions include: theory and practice of sunlight concentrators; an overview of concentrator PV activities; a description of concentrator solar cells; design and technology of modules and systems; manufacturing aspects; and a market study.

  5. A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris.

    Science.gov (United States)

    Zhu, Wenyi; Du, Yijie; Meng, Hong; Dong, Yinmao; Li, Li

    2017-07-11

    Tribulus terrestris L. (TT) is an annual plant of the family Zygophyllaceae that has been used for generations to energize, vitalize, and improve sexual function and physical performance in men. The fruits and roots of TT have been used as a folk medicine for thousands of years in China, India, Sudan, and Pakistan. Numerous bioactive phytochemicals, such as saponins and flavonoids, have been isolated and identified from TT that are responsible alone or in combination for various pharmacological activities. This review provides a comprehensive overview of the traditional applications, phytochemistry, pharmacology and overuse of TT and provides evidence for better medicinal usage of TT.

  6. Pharmacological studies of the lung with PET

    International Nuclear Information System (INIS)

    Syrota, A.

    1986-10-01

    Positron emission tomography (PET), known to be used for lung ventilation and perfusion studies, can also be used in pharmacology to obtain information that is otherwise not available. The lung takes up biologically active substances which can be inactivated or activated, and synthesises and releases others. Such information in man has been obtained from samples of human lungs, or from in vivo first-pass studies, invasive or not, as well as from in vivo kinetic studies using external detection methods with scintillation cameras. PET provides now quantitative regional data in the human lung

  7. Chemistry and Pharmacology of Citrus sinensis

    Directory of Open Access Journals (Sweden)

    Juan Manuel J. Favela-Hernández

    2016-02-01

    Full Text Available Presently the search for new drugs from natural resources is of growing interest to the pharmaceutical industry. Natural products have been the source of new drugs since ancient times. Plants are a good source of secondary metabolites which have been found to have beneficial properties. The present study is a review of the chemistry and pharmacology of Citrus sinensis. This review reveals the therapeutic potential of C. sinensis as a source of natural compounds with important activities that are beneficial for human health that could be used to develop new drugs.

  8. [Pharmacological aspects of pain research in Germany].

    Science.gov (United States)

    Niederberger, E; Kuner, R; Geißlinger, G

    2015-10-01

    In spite of several approved analgesics, the therapy of pain still constitutes a challenge due to the fact that the drugs do not exert sufficient efficacy or are associated with severe side effects. Therefore, the development of new and improved painkillers is still of great importance. A number of highly qualified scientists in Germany are investigating signal transduction pathways in pain, effectivity of new drugs and the so far incompletely investigated mechanisms of well-known analgesics in preclinical and clinical studies. The highlights of pharmacological pain research in Germany are summarized in this article.

  9. Reappraisal of GIP Pharmacology for Metabolic Diseases

    DEFF Research Database (Denmark)

    Finan, Brian; Müller, Timo D; Clemmensen, Christoffer

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursue...... be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits....

  10. Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

    Science.gov (United States)

    Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

    2015-10-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  11. Pharmacologic modeling of primary mitochondrial respiratory chain dysfunction in zebrafish.

    Science.gov (United States)

    Byrnes, James; Ganetzky, Rebecca; Lightfoot, Richard; Tzeng, Michael; Nakamaru-Ogiso, Eiko; Seiler, Christoph; Falk, Marni J

    2017-07-18

    Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology. Here, we characterize four pharmacologic inhibitor models of mitochondrial RC dysfunction in early larval zebrafish, including rotenone (complex I inhibitor), azide (complex IV inhibitor), oligomycin (complex V inhibitor), and chloramphenicol (mitochondrial translation inhibitor that leads to multiple RC complex dysfunction). A range of concentrations and exposure times of each RC inhibitor were systematically evaluated on early larval development, animal survival, integrated behaviors (touch and startle responses), organ physiology (brain death, neurologic tone, heart rate), and fluorescence-based analyses of mitochondrial physiology in zebrafish skeletal muscle. Pharmacologic RC inhibitor effects were validated by spectrophotometric analysis of Complex I, II and IV enzyme activities, or relative quantitation of ATP levels in larvae. Outcomes were prioritized that utilize in vivo animal imaging and quantitative behavioral assessments, as may optimally inform the translational potential of pre-clinical drug screens for future clinical study in human mitochondrial disease subjects. The RC complex inhibitors each delayed early embryo development, with short-term exposures of these three agents or chloramphenicol from 5 to 7 days

  12. Pharmacological treatment for memory disorder in multiple sclerosis.

    Science.gov (United States)

    He, Dian; Zhang, Yun; Dong, Shuai; Wang, Dongfeng; Gao, Xiangdong; Zhou, Hongyu

    2013-12-17

    authors. We contacted principal investigators of included studies for additional data or confirmation. We included seven randomised controlled trials (RCTs) involving 625 people mostly with relapsing-remitting, secondary-progressive and primary-progressive MS, evaluating the absolute efficacy of donepezil, ginkgo biloba, memantine and rivastigmine versus placebo in improving memory performance with diverse assessment scales. Overall, clinical and methodological heterogeneities existed across these studies. Moreover, most of them had methodological limitations on non-specific selections of targeted sample, non-matched variables at baseline or incomplete outcome data (high attrition bias). Only the two studies on donepezil had clinical and methodological homogeneity and relatively low risks for bias. One RCT evaluating estriol versus placebo is currently ongoing.We could not carry out a meta-analysis due to the heterogeneities across studies and the high attrition bias. A subgroup analysis for donepezil versus placebo showed no treatment effects on total recall on the Selective Reminding Test (mean difference (MD) 1.68; 95% confidence interval (CI) -2.21 to 5.58), total correct scores on the 10/36 Spatial Recall Test (MD -0.93; 95% CI -3.18 to 1.32), the Symbol Digit Modalities Test (MD -1.27; 95% CI -3.15 to 0.61) and the Paced Auditory Serial Addition Test (2+3 sec) (MD 2.23; 95% CI -1.87 to 6.33). Concerning safety, the main adverse events were: diarrhoea (risk ratio (RR) 3.88; 95% CI 1.66 to 9.05), nausea (RR 1.71; 95% CI 0.93 to 3.18) and abnormal dreams (RR 2.91; 95% CI 1.38 to 6.14). However, the results in both studies were subjected to a serious imprecision resulting from the small sample sizes and the low power of test (lower than 80%), which contributed to a moderate quality of the evidence. No serious adverse events were attributed to the treatments in all experimental groups. We found no convincing evidence to support the efficacy of pharmacological symptomatic

  13. The pharmacological management of metabolic syndrome.

    Science.gov (United States)

    Rask Larsen, Julie; Dima, Lorena; Correll, Christoph U; Manu, Peter

    2018-04-01

    The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice. Areas covered: A Medline literature search was performed to identify clinical trials and meta-analyses related to the therapy of dyslipidemia, arterial hypertension, glucose metabolism and obesity published in the past decade. Expert commentary: Our recommendation for first-line pharmacological are statins for dyslipidemia, renin-angiotensin-aldosteron system inhibitors for arterial hypertension, metformin or sodium/glucose cotransporter 2 inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1RAs) for glucose intolerance, and the GLP-1RA liraglutide for achieving body weight and waist circumference reduction.

  14. Neuro-pharmacological functional MRI of epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji [Okayama Univ. (Japan). School of Medicine; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

    2000-03-01

    We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

  15. Pharmacological Effects of Niacin on Acute Hyperlipemia.

    Science.gov (United States)

    la Paz, Sergio Montserrat-de; Bermudez, Beatriz; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2016-01-01

    The well-known changes in modern lifestyle habits including over nutrition and physical inactivity have led to striking adverse effects on public health (e.g., obesity, diabetes, and metabolic syndrome) over recent decades. One noticeable consequence is exaggerated and prolonged state of postprandial hyperlipemia due to the ingestion of multiple fat-enriched meals during the course of a day. Postprandial (non-fasting) hyperlipemia is characterized by increased blood levels of exogenous triglycerides (TG) in the form of apolipoprotein (apo) B48-containing TG-rich lipoproteins (TRL), which have a causal role in the pathogenesis and progression of cardiovascular disease (CVD). The cardiovascular benefits of lifestyle modification (healthy diet and exercise) and conventional lipid-lowering therapies (e.g., statins, fibrates, and niacin) could involve their favourable effects on postprandial metabolism. Pharmacologically, niacin has been used as an athero-protective drug for five decades. Studies have since shown that niacin may decrease fasting levels of plasma verylow- density lipoproteins (VLDL), low-density lipoprotein cholesterol (LDL-C), and lipoprotein [a] (Lp[a]), while may increase high-density lipoprotein cholesterol (HDL-C). Herein, the purpose of this review was to provide an update on effects and mechanisms related to the pharmacological actions of niacin on acute hyperlipemia.

  16. Phytochemical and pharmacological review of Lagenaria sicereria.

    Science.gov (United States)

    Prajapati, Rakesh P; Kalariya, Manisha; Parmar, Sachin K; Sheth, Navin R

    2010-10-01

    Lagenaria siceraria (Molina) standley (LS) (Family: Cucurbitaceae) is an annual herbaceous climbing plant with a long history of traditional medicinal uses in many countries, especially in tropical and subtropical regions. Since ancient times the climber has been known for its curative properties, and has been utilized for treatment of various ailments, including jaundice, diabetes, ulcer, piles, colitis, insanity, hypertension, congestive cardiac failure (CCF), and skin diseases. Its fruit pulp is used both as an emetic and purgative, and for its cooling, diuretic, antibilious, and pectoral properties. Boiled in oil this pulp is used to treat rheumatism and insomnia. A wide range of chemical compounds including sterols, terpenoids, flavonoids, and saponins have been isolated from the species. Its extracts have been found to possess various pharmacological activities. Below, we give a comprehensive review of its ethnomedical uses, chemical constituents, and pharmacological profile as a medicinal plant. Particular attention is given to its analgesic, anti-inflammatory, antihyperlipidemic, diuretic, hepatoprotective, anthelmintic, and antibacterial effects so that its potential uses in pharmaceutics can be better evaluated.

  17. Phytochemical and pharmacological review of Lagenaria sicereria

    Directory of Open Access Journals (Sweden)

    Rakesh P Prajapati

    2010-01-01

    Full Text Available Lagenaria siceraria (Molina standley (LS (Family: Cucurbitaceae is an annual herbaceous climbing plant with a long history of traditional medicinal uses in many countries, especially in tropical and subtropical regions. Since ancient times the climber has been known for its curative properties, and has been utilized for treatment of various ailments, including jaundice, diabetes, ulcer, piles, colitis, insanity, hypertension, congestive cardiac failure (CCF, and skin diseases. Its fruit pulp is used both as an emetic and purgative, and for its cooling, diuretic, antibilious, and pectoral properties. Boiled in oil this pulp is used to treat rheumatism and insomnia. A wide range of chemical compounds including sterols, terpenoids, flavonoids, and saponins have been isolated from the species. Its extracts have been found to possess various pharmacological activities. Below, we give a comprehensive review of its ethnomedical uses, chemical constituents, and pharmacological profile as a medicinal plant. Particular attention is given to its analgesic, anti-inflammatory, antihyperlipidemic, diuretic, hepatoprotective, anthelmintic, and antibacterial effects so that its potential uses in pharmaceutics can be better evaluated.

  18. Multiple sclerosis: general features and pharmacologic approach

    International Nuclear Information System (INIS)

    Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

    2009-01-01

    Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

  19. DIVERSE POTENTIAL AND PHARMACOLOGICAL STUDIES OF ARGININE

    Directory of Open Access Journals (Sweden)

    Anju Meshram

    2015-09-01

    Full Text Available Arginine is metabolically flexible amino acid with major role in protein synthesis and detoxification of ammonia. It is involved in several metabolic pathways for the production of biologically active compounds such as creatine, nitric oxide, ornithine, glutamate, agmatine, citrulline and polyamines. Regarding this all, we review the crucial role of arginine in metabolism, diversified prospective uses and pharmacological applications. Arginine plays an important role in the treatment of tumorigenesis, asthama, gastric, erectile dysfunction, apoptosis, melanoma and congestive heart failure. Ability to produce nitric oxide offers various applications as in the prevention of age and hair loss. It serves as a precursor of creatine with ergogenic potential. The ability to increase endogenous growth hormone makes arginine a preferred supplement for the improvement of physical performance. In the present study details about the pharmacological applications of arginine based on modern scientific investigations have been discussed. There are immense properties hidden in arginine that need to be explored using the scientific investigations to make it beneficial for the medicine and human health. More research is needed to evaluate the role of arginine supplementation on exercise performance and training adaptations in healthy and diseased populations before taking any conclusions.

  20. Pharmacological treatment of diabetic neuropathic pain.

    Science.gov (United States)

    Smith, Howard S; Argoff, Charles E

    2011-03-26

    Neuropathic pain continues to be a difficult and challenging clinical issue to deal with effectively. Painful diabetic polyneuropathy is a complex pain condition that occurs with reasonable frequency in the population and it may be extremely difficult for clinicians to provide patients with effective analgesia. Chronic neuropathic pain may occur in approximately one of every four diabetic patients. The pain may be described as burning or a deep-seated ache with sporadic paroxysms of lancinating painful exacerbations. The pain is often constant, moderate to severe in intensity, usually primarily involves the feet and generally tends to worsen at night. Treatment may be multimodal but largely involves pharmacological approaches. Pharmacological therapeutic options include antidepressants (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), α2δ ligands and topical (5%) lidocaine patch. Other agents may be different antiepileptic drugs (carbamazepine, lamotrigine, topiramate), topical capsaicin, tramadol and other opioids. Progress continues with respect to understanding various mechanisms that may contribute to painful diabetic neuropathy. Agents that may hold some promise include neurotrophic factors, growth factors, immunomodulators, gene therapy and poly (adenosine diphosphate-ribose) polymerase inhibitors. It is hoped that in the future clinicians will be able to assess patient pathophysiology, which may help them to match optimal therapeutic agents to target individual patient aberrant mechanisms.