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Sample records for analogues potential treatment

  1. Syntheses And Evaluation Of Asymmetric Curcumin Analogues As Potential Multifunctional Agents For The Treatment Of Alzheimer's Disease.

    Science.gov (United States)

    Zhai, Peng; Xia, Chun-Li; Tan, Jia-Heng; Li, Ding; Ou, Tian-Miao; Huang, Shi-Liang; Gu, Lian-Quan; Huang, Zhi-Shu

    2015-01-01

    A series of new asymmetric curcumin analogues were synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. Our results showed that most of these synthetic compounds had better inhibitory properties against Aβ aggregation compared with curcumin, and better anti-oxidative properties compared with the reference compound Trolox through the study of oxygen radical absorbance capacity (ORAC). Some compounds showed good properties in selectively chelating metal ions such as copper and iron. Besides, some compounds were found to be able to dissociate Aβ protein which had already aggregated. The structure-activity relationships (SAR) of these synthetic compounds were studied. The present investigation indicated that our synthetic asymmetric curcumin derivatives could be potential multifunctional agents for the treatment of Alzheimer's disease (AD).

  2. Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

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    Katarzyna M. Terlikowska

    2014-11-01

    Full Text Available Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies.

  3. Pharmacological Analysis of Vorinostat Analogues as Potential Anti-tumor Agents Targeting Human Histone Deacetylases: an Epigenetic Treatment Stratagem for Cancers.

    Science.gov (United States)

    Praseetha, Sugathan; Bandaru, Srinivas; Nayarisseri, Anuraj; Sureshkumar, Sivanpillai

    2016-01-01

    Alteration of the acetylation status of chromatin and other non-histone proteins by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment of cancers. The present study was sought to identify compounds with positive pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by Cai et al, 2015 formed the test compounds for the present pharmacological evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in comparison to all the compounds in the analogue dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify compounds with even better high affinity and pharmacological profile than 6H and Vorinostat, virtual screening was performed. A total of 83 compounds similar to Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695 (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and 6H, were the best docked compounds among the virtually screened compounds. However, in spite of having good affinity, none of the virtually screened compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report Vorinostat hydroxamate analogue 6H to be a potential candidate for HDAC inhibition in treatment of cancers through an epigenetic strategy.

  4. Desert spring mounds: a potential analogue to Martian arid environments?

    Science.gov (United States)

    Franchi, F.; Frisia, S.

    2017-09-01

    Spring carbonates have been often considered as putative analogues of Martian arid environments. On Earth these are believed to form by the interaction of highly saline water and microbial communities, which favor the formation of authigenic micrite. Here we present new data from spring mounds in the western Makgadikgadi Pan (Botswana) and the Great Artesian Basin (South Australia). In both areas, upwelling of ground water give rise to mounds and layered deposits which are close morphological analogues of landforms documented on Mars. The authigenic carbonates and evaporites associated with the spring mounds retain evidence of microbial microfabric founded elsewhere, pointing to the potential existence of similar microbial in the extreme Martian conditions.

  5. Alkaloids of family Amaryllidaceae and their analogues as potential drugs

    OpenAIRE

    Kavková, Zuzana

    2016-01-01

    Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Zuzana Kavková Supervisor: doc. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Alkaloids of family Amaryllidaceae and their analogues as potential drugs The object of this diploma thesis was to prepare derivatives of alkaloids of Amaryllidaceae family and to deal with their biological activity. These alkaloids are famous for their antibacterial, antiinfectives, a...

  6. Current insulin analogues in the treatment of diabetes: emphasis on type 2 diabetes.

    Science.gov (United States)

    Esposito, Katherine; Giugliano, Dario

    2012-02-01

    Although traditionally used as a final treatment option, early use of insulin is a therapeutic option after metformin failure in type 2 diabetes. Injection of native insulin lacks the rapid onset of action after food ingestion and the chronic maintenance of a steady-state low-level basal insulin in fasting periods. These limitations have fuelled the development of insulin analogues, which mainly fall into two different categories: short-acting and long-acting analogues. We review the recent literature investigating the efficacy and safety of insulin analogues in human diabetes, with emphasis on type 2 diabetes, as about 30% of these patients are being treated with insulin. We also examine novel developments in this area, including the new long-acting basal analogues whose longer duration of action might reduce dosing frequency to three times a week. Insulin analogues show some advantage compared with native insulin. However, improvements in reducing their pharmacological variability would be expected to lower the risk of hypoglycemia and hyperglycemia, as well as to simplify and perhaps also encourage optimal insulin titration in real-life clinical practice. Extending the duration of insulin effect would also allow for greater flexibility and potentially reduce the frequency of blood glucose monitoring.

  7. Potential of carbon nanotube field effect transistors for analogue circuits

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    Khizar Hayat

    2013-11-01

    Full Text Available This Letter presents a detailed comparison of carbon nanotube field effect transistors (CNFETs and metal oxide semiconductor field effect transistors (MOSFETs with special focus on carbon nanotube FET's potential for implementing analogue circuits in the mm-wave and sub-terahertz range. The latest CNFET lithographic dimensions place it at-par with complementary metal oxide semiconductor in terms of current handling capability, whereas the forecasted improvement in the lithography enables the CNFETs to handle more than twice the current of MOSFETs. The comparison of RF parameters shows superior performance of CNFETs with a g(m, f(T and f(max of 2.7, 2.6 and 4.5 times higher, respectively. MOSFET- and CNFET-based inverter, three-stage ring oscillator and LC oscillator have been designed and compared as well. The CNFET-based inverters are found to be ten times faster, the ring oscillator demonstrates three times higher oscillation frequency and CNFET-based LC oscillator also shows improved performance than its MOSFET counterpart.

  8. Potential of carbon nanotube field effect transistors for analogue circuits

    KAUST Repository

    Hayat, Khizar

    2013-05-11

    This Letter presents a detailed comparison of carbon nanotube field effect transistors (CNFETs) and metal oxide semiconductor field effect transistors (MOSFETs) with special focus on carbon nanotube FET\\'s potential for implementing analogue circuits in the mm-wave and sub-terahertz range. The latest CNFET lithographic dimensions place it at-par with complementary metal oxide semiconductor in terms of current handling capability, whereas the forecasted improvement in the lithography enables the CNFETs to handle more than twice the current of MOSFETs. The comparison of RF parameters shows superior performance of CNFETs with a g m , f T and f max of 2.7, 2.6 and 4.5 times higher, respectively. MOSFET- and CNFET-based inverter, three-stage ring oscillator and LC oscillator have been designed and compared as well. The CNFET-based inverters are found to be ten times faster, the ring oscillator demonstrates three times higher oscillation frequency and CNFET-based LC oscillator also shows improved performance than its MOSFET counterpart.

  9. Neurotoxicity Caused by the Treatment with Platinum Analogues

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    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  10. Meglitinide analogues in the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Landgraf, R

    2000-11-01

    Type 2 diabetes mellitus is a complex heterogenous metabolic disorder in which peripheral insulin resistance and impaired insulin release are the main pathogenetic factors. The rapid response of the pancreatic beta-cells to glucose is already markedly disturbed in the early stages of type 2 diabetes mellitus. The consequence is often postprandial hyperglycaemia, which seems to be extremely important in the development of secondary complications, especially macrovascular disease. Therefore one of the main aims of treatment is to minimise blood glucose oscillations and attain near-normal glycosylated haemoglobin levels. Meglitinide analogues belong to a new family of insulin secretagogues which stimulate insulin release by inhibiting ATP-sensitive potassium channels of the beta-cell membrane via binding to a receptor distinct from that of sulphonylureas (SUR1/KIR 6.2). The pharmacokinetic and pharmacodynamic properties of repaglinide, the first drug of these new antihyperglycaemic agents on the market, and of nateglinide, which will be available soon, differ markedly from the currently used sulphonylureas [mainly glibenclamide (glyburide) and glimepiride]. Repaglinide and nateglinide are absorbed rapidly, stimulate insulin release within a few minutes, are rapidly metabolised in the liver and are mainly excreted in the bile. Therefore, following preprandial administration of these drugs, insulin is more readily available during and just after the meal. This leads to a significant reduction in postprandial hyperglycaemia without the danger of hypoglycaemia between meals. The short action of these compounds and biliary elimination makes repaglinide and nateglinide especially suitable for patients with type 2 diabetes mellitus who would like to have a more flexible lifestyle, need more flexibility because of unplanned eating behaviour (e.g. geriatric patients) or in whom one of the other first-line antidiabetic drugs, i.e. metformin, is strictly contraindicated (e

  11. Cyclobutanone Analogues of β-Lactam Antibiotics: β-Lactamase Inhibitors with Untapped Potential?

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    Devi, Prarthana; Rutledge, Peter J

    2017-02-16

    β-Lactam antibiotics have been used for many years to treat bacterial infections. However the effective treatment of an increasing range of microbial infections is threatened by bacterial resistance to β-lactams: the prolonged, widespread (and at times reckless) use of these drugs has spawned widespread resistance, which renders them ineffective against many bacterial strains. The cyclobutanone ring system is isosteric with β-lactam: in cyclobutanone analogues, the eponymous cyclic amide is replaced with an all-carbon ring, the amide N is substituted by a tertiary C-H α to a ketone. Cyclobutanone analogues of various β-lactam antibiotics have been investigated over the last 35 years, initially as prospective antibiotics in their own right and inhibitors of the β-lactamase enzymes that impart resistance to β-lactams. More recently they have been tested as inhibitors of other serine proteases and as mechanistic probes of β-lactam biosynthesis. Cyclobutanone analogues of the penam ring system are the first reversible inhibitors with moderate activity against all classes of β-lactamase; other compounds from this family inhibit Streptomyces R61 dd-carboxypeptidase/transpeptidase, human neutrophil elastase and porcine pancreatic elastase. But has their potential as enzyme inhibitors been fully exploited? Challenges in synthesising diversely functionalised cyclobutanone derivatives mean that only a limited number have been made (with limited structural diversity) and evaluated. This review surveys the different synthetic approaches that have been taken to these compounds, the investigations made to evaluate their biological activity and prospects for future developments in this area. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Vitamin E analogues and immune response in cancer treatment

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Neužil, Jiří

    2007-01-01

    Roč. 76, - (2007), s. 463-491 ISSN 0083-6729 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : vitamin E analogues * inducers of apoptosis * immune surveillance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.889, year: 2007

  13. Deoxyfluoro-d-trehalose (FDTre) analogues as potential PET probes for imaging mycobacterial infection.

    Science.gov (United States)

    Rundell, Sarah R; Wagar, Zachary L; Meints, Lisa M; Olson, Claire D; O'Neill, Mara K; Piligian, Brent F; Poston, Anne W; Hood, Robin J; Woodruff, Peter J; Swarts, Benjamin M

    2016-09-28

    Mycobacterium tuberculosis, the etiological agent of human tuberculosis, requires the non-mammalian disaccharide trehalose for growth and virulence. Recently, detectable trehalose analogues have gained attention as probes for studying trehalose metabolism and as potential diagnostic imaging agents for mycobacterial infections. Of particular interest are deoxy-[(18)F]fluoro-d-trehalose ((18)F-FDTre) analogues, which have been suggested as possible positron emission tomography (PET) probes for in vivo imaging of M. tuberculosis infection. Here, we report progress toward this objective, including the synthesis and conformational analysis of four non-radioactive deoxy-[(19)F]fluoro-d-trehalose ((19)F-FDTre) analogues, as well as evaluation of their uptake by M. smegmatis. The rapid synthesis and purification of several (19)F-FDTre analogues was accomplished in high yield using a one-step chemoenzymatic method. Conformational analysis of the (19)F-FDTre analogues using NMR and molecular modeling methods showed that fluorine substitution had a negligible effect on the conformation of the native disaccharide, suggesting that fluorinated analogues may be successfully recognized and processed by trehalose metabolic machinery in mycobacteria. To test this hypothesis and to evaluate a possible route for delivery of FDTre probes specifically to mycobacteria, we showed that (19)F-FDTre analogues are actively imported into M. smegmatis via the trehalose-specific transporter SugABC-LpqY. Finally, to demonstrate the applicability of these results to the efficient preparation and use of short-lived (18)F-FDTre PET radiotracers, we carried out (19)F-FDTre synthesis, purification, and administration to M. smegmatis in 1 hour.

  14. Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent.

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    Panpan Wu

    Full Text Available Ursolic acid (UA is a naturally bioactive compound that possesses potential anti-diabetic activity. The relatively safe and effective molecule intrigued us to further explore and to improve its anti-diabetic activity. In the present study, a series of novel UA analogues was synthesized and their structures were characterized. Their bioactivities against the α-glucosidase from baker's yeast were determined in vitro. The results suggested that most of the analogues exhibited significant inhibitory activity, especially analogues 8b and 9b with the IC50 values of 1.27 ± 0.27 μM (8b and 1.28 ± 0.27 μM (9b, which were lower than the other analogues and the positive control. The molecular docking and 2D-QSAR studies were carried out to prove that the C-3 hydroxyl could interact with the hydrophobic region of the active pocket and form hydrogen bonds to increase the binding affinity of ligand and the homology modelling protein. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from UA analogues.

  15. New Chiral Ebselen Analogues with Antioxidant and Cytotoxic Potential

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    Agata J. Pacuła

    2017-03-01

    Full Text Available New chiral camphane-derived benzisoselenazol-3(2H-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives was evaluated and compared to the reactivity of a series of N-amino acid benzisoselenazol-3(2H-ones obtained by a modified procedure involving the improved synthesis and isolation of the diseleno bis(dibenzoic acid. The most efficient peroxide scavengers, N-bornyl and N-leucine methyl ester benzisoselenazol-3(2H-ones, were further evaluated as cytotoxic agents on four cancer cell lines (MCF-7, HEP G2, HL 6, and DU 145 and normal cell line PNT1A. The highest antiproliferative potential was evaluated for two compounds bearing a 3-methylbutyl carbon chain, N-leucine methyl ester and N-3-methylbutyl benzisoselenazol-3(2H-ones.

  16. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

  17. Design, synthesis, and biological evaluation of curcumin analogues as multifunctional agents for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Chen, Shang-Ying; Chen, Yuan; Li, Yan-Ping; Chen, Shu-Han; Tan, Jia-Heng; Ou, Tian-Miao; Gu, Lian-Quan; Huang, Zhi-Shu

    2011-09-15

    A series of novel curcumin analogues were designed, synthesized, and evaluated as potential multifunctional agents for the treatment of AD. The in vitro studies showed that these compounds had better inhibitory properties against Aβ aggregation than curcumin. Superior anti-oxidant properties (better than the reference compound Trolox) of these compounds were observed by the oxygen radical absorbance capacity (ORAC) method and a cell-based assay using DCFH-DA as a probe. In addition they were able to chelate metals such as iron and copper and decrease metal-induced Aβ aggregation. The structure-activity relationships were discussed. The results suggested that our curcumin analogues could be selected as multifunctional agents for further investigation of AD treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. The combination of insulin and GLP-1 analogues in the treatment of type 2 diabetes

    NARCIS (Netherlands)

    van der Klauw, M. M.; Wolffenbuttel, B. H. R.

    2012-01-01

    GLP-1 analogues have been proven to be effective in the treatment of type 2 diabetes mellitus. They stimulate insulin production and secretion, and suppress glucagon secretion, depending on the blood glucose level. They also have an effect on the brain, enhancing satiety, and on the gut, where they

  19. Assessment of efficiency of application of various analogues of insulin in treatment of diabetes type 2

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    Rodionova T.l.

    2014-09-01

    Full Text Available Purpose: to estimate efficiency of treatment of analogues of insulin Glargin and insulin Detemir in patients with diabetes type 2. Material and methods. 147 patients with diabetes type 2 which have been initially receiving combined therapy by oral antihyperglycemic agent and NPH-insulin have been under the study. Level of glycated hemoglobin has been defined in 3 and 6 months for the general assessment of control of aglycemia. Results. According to the study the use of insulin analogues (Detemir, Glargin versus NPH insulin for 6 months allowed to reach individual target values of glycemia in 70% of patients with diabetes type 2 with a low risk of hypoglycemia. Conclusion. The use in clinical practice of modern insulin analogues and simple algorithm for dose titration, allows simulating as closely as possible the physiological insulin secretion, helping to achieve compensation of carbohydrate metabolism in larger numbers of patients in comparison with NPH insulin.

  20. Analogues of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide

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    Grassi, Lucia; Maisetta, Giuseppantonio; Maccari, Giuseppe; Esin, Semih; Batoni, Giovanna

    2017-04-01

    The frog skin-derived peptide Temporin 1Tb (TB) has gained increasing attention as novel antimicrobial agent for the treatment of antibiotic-resistant and/or biofilm-mediated infections. Nevertheless, such a peptide possesses a preferential spectrum of action against Gram-positive bacteria. In order to improve the therapeutic potential of TB, the present study evaluated the antibacterial and antibiofilm activities of two TB analogues against medically relevant bacterial species. Of the two analogues, TB_KKG6A has been previously described in the literature, while TB_L1FK is a new analogue designed by us through statistical-based computational strategies. Both TB analogues displayed a faster and stronger bactericidal activity than the parental peptide, especially against Gram-negative bacteria in planktonic form. Differently from the parental peptide, TB_KKG6A and TB_L1FK were able to inhibit the formation of Staphylococcus aureus biofilms by more than 50% at 12 μM, while only TB_KKG6A prevented the formation of Pseudomonas aeruginosa biofilms at 24 μM. A marked antibiofilm activity against preformed biofilms of both bacterial species was observed for the two TB analogues when used in combination with EDTA. Analysis of synergism at the cellular level suggested that the antibiofilm activity exerted by the peptide-EDTA combinations against mature biofilms might be due mainly to a disaggregating effect on the extracellular matrix in the case of S. aureus, and to a direct activity on biofilm-embedded cells in the case of P. aeruginosa. Both analogues displayed a low hemolytic effect at the active concentrations and, overall, TB_L1FK resulted less cytotoxic towards mammalian cells. Collectively, the results obtained demonstrated that subtle changes in the primary sequence of TB may provide TB analogues that, used alone or in combination with adjuvant molecules such as EDTA, exhibit promising features against both planktonic and biofilm cells of medically relevant

  1. Potential therapeutic applications of human anti-Müllerian hormone (AMH) analogues in reproductive medicine.

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    Kushnir, Vitaly A; Seifer, David B; Barad, David H; Sen, Aritro; Gleicher, Norbert

    2017-09-01

    Members of the transforming growth factor-beta (TGF-beta) superfamily are key regulators of various physiological processes. Anti-Müllerian hormone (AMH) which is also commonly known as Müllerian-inhibiting substance (MIS) is a member of the TGF-beta superfamily and an important regulator of reproductive organ differentiation and ovarian follicular development. While AMH has been used for diagnostic purposes as a biomarker for over 15 years, new potential therapeutic applications of recombinant human AMH analogues are now emerging as pharmacologic agents in reproductive medicine. Therapeutic uses of AMH in gonadal tissue may provide a unique opportunity to address a broad range of reproductive themes, like contraception, ovulation induction, onset of menopause, and fertility preservation, as well as specific disease conditions, such as polycystic ovarian syndrome (PCOS) and cancers of the reproductive tract. This review explores the most promising therapeutic applications for a novel class of drugs known as AMH analogues with agonist and antagonist functions.

  2. In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors.

    Science.gov (United States)

    Park, Jae B

    2017-12-13

    p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR) spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; -20 to -39) and several analogues with ΔE; -34 to -39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; -34 to -39) and in silico scores (Avg. score; -27.5 to -29.3). Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; -27.5 to -29.3) were found to inhibit p38 MAPK by 27-31% ( p silico score (Avg. score; -29.2) inhibited p38 MAPK (IC 50 = 9.9 μM) a little better than its methyl ester with best in silico score (Avg. score; -29.3). To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22-73% ( p silico and in vitro assay approach may be a useful and efficient solution as a functional screening approach in searching new lead compounds for targeted molecules.

  3. Structural Correlation of Some Heterocyclic Chalcone Analogues and Evaluation of Their Antioxidant Potential

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    Hoong-Kun Fun

    2013-09-01

    Full Text Available A series of six novel heterocyclic chalcone analogues 4(a–f has been synthesized by condensing 2-acetyl-5-chlorothiophene with benzaldehyde derivatives in methanol at room temperature using a catalytic amount of sodium hydroxide. The newly synthesized compounds are characterized by IR, mass spectra, elemental analysis and melting point. Subsequently; the structures of these compounds were determined using single crystal X-ray diffraction. All the synthesized compounds were screened for their antioxidant potential by employing various in vitro models such as DPPH free radical scavenging assay, ABTS radical scavenging assay, ferric reducing antioxidant power and cupric ion reducing antioxidant capacity. Results reflect the structural impact on the antioxidant ability of the compounds. The IC50 values illustrate the mild to good antioxidant activities of the reported compounds. Among them, 4f with a p-methoxy substituent was found to be more potent as antioxidant agent.

  4. Library construction and biological evaluation of enmein-type diterpenoid analogues as potential anticancer agents.

    Science.gov (United States)

    Li, Dahong; Xu, Shengtao; Cai, Hao; Pei, Lingling; Wang, Lei; Wu, Xiaoming; Yao, Hequan; Jiang, Jieyun; Sun, Yijun; Xu, Jinyi

    2013-05-01

    A library of promising enmein-type 14-O-diterpenoid derivatives was constructed from a commercially available kaurene-type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel-7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC-803 mice). These results warrant further preclinical investigations of these diterpenoid-based analogues as potential novel anticancer chemotherapeutics. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Applications of natural analogue studies to Yucca Mountain as a potential high level radioactive waste repository

    International Nuclear Information System (INIS)

    1995-02-01

    The 5-member group convened in Las Vegas, Nov. 11-13, 1991, to clarify the extent to which studies of natural analogues can assist the Yucca Mountain site characterization (SC) project. This document is to provide guidance and recommendations to DOE for the implementation of natural analogue studies in the SC program. Performance assessment, integrity of engineered barriers, and communication to the public and the scientific community are stressed. The reference design being developed by Babcock ampersand Wilcox Fuel Company are reviewed. Guidelines for selecting natural analogues are given. Quality assurance is discussed. Recommendations are given for developing an effective natural analogue program within the SC program

  6. Vasopressin and its analogues for the treatment of refractory hypotension in neonates.

    Science.gov (United States)

    Shivanna, Binoy; Rios, Danielle; Rossano, Joseph; Fernandes, Caraciolo J; Pammi, Mohan

    2013-03-28

    not be done reliably by title and abstract. We resolved any differences by mutual discussion. We designed electronic forms for trial inclusion/exclusion, data extraction, and for requesting additional published information from authors of the original reports. Our search did not identify any completed or ongoing trials that met our inclusion criteria. Three studies that did not include neonates and one study where the objective was not to treat neonates with refractory hypotension were excluded. There is insufficient evidence to recommend or refute the use of vasopressin or its analogues in the treatment of refractory hypotension in neonates. Well-designed, adequately powered, randomized controlled studies are necessary to address efficacy, optimal dosing, safety and long-term neurodevelopmental and pulmonary outcomes. 

  7. Potentiation of Muscarinic and α -adrenergic Responses by an Analogue of Guanosine 5'-triphosphate

    Science.gov (United States)

    Evans, M. G.; Marty, A.

    1986-06-01

    Ca2+-dependent K+ and Cl- currents were recorded in isolated and dialyzed rat lacrimal gland cells by use of the tight-seal whole-cell recording technique. Under control conditions, application of acetylcholine (0.5-1.0 μ M) resulted in the full activation of both types of current. When 50-200 μ M guanosine 5'-[γ -thio]triphosphate (GTP[S], a nonhydrolyzable GTP analogue) was added to the intracellular solution, activation of both currents was seen with 1 nM acetylcholine, a dose 1/100th that needed under control conditions. Dialysis with solutions containing 200 μ M GTP or cAMP had no, or only slight, potentiation effects. The effects of GTP[S] were obtained only when ATP was included in the intracellular solution. The potentiated responses to acetylcholine were blocked by increasing 10-fold the intracellular Ca2+-buffering capacity and were not dependent on external Ca2+. Thus, the potentiated responses appeared to result from a release of Ca2+ from internal stores. GTP[S] also greatly potentiated the Ca2+-dependent adrenergic (norepinephrine) response of this preparation. In addition, GTP[S] elicited in some cells transient responses without application of acetylcholine or norepinephrine. Finally, rapid and sustained responses were seen as soon as the cells were dialyzed with inositol trisphosphate (20 μ M). These findings are discussed in terms of a possible role of a GTP-binding protein as a link between activation of muscarinic or adrenergic receptors and initiation of Ca2+ release by inositol trisphosphate.

  8. From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents

    International Nuclear Information System (INIS)

    Spielvogel, B.F.; Sood, Anup; Duke Univ., Durham, NC; Shaw, B.R.; Hall, I.H.

    1991-01-01

    Isoelectronic and isostructural boron analogues of the α-amino acids ranging from simple glycine analogues such as H 3 NBH 2 COOH and Me 2 NHBH 2 COOH to alanine analogues have been synthesised. A diverse variety of analogues, including precursors and derivatives (such as peptides) have potent pharmacological activity, including anticancer, antiinflammatory, analgesic, and hypolipidemic activity in animal model studies and in vitro cell cultures. Boronated nucleosides and (oligo)nucleotides, synthetic oligonucleotide analogues of ''antisense'' agents interact with a complementary nucleic acid sequence blocking the biological effect of the target sequence. Nucleosides boronated on the pyrimidine and purine bases have been prepared. It has been established that an entirely new class of nucleic acid derivatives is feasible in which one of the non-bridging oxygens in the internucleotide phosphodiester linkage can be replaced by an isoelectronic analogue, the borane group, (BH 3 ). The boronated oligonucleotides can be viewed as hybrids of the normal oxygen oligonucleotides and the methylphosphonate oligonucleotides. (author)

  9. Effects of metformin on body weight in patients with type 2 diabetes mellitus,receiving insulin analogue treatment

    Directory of Open Access Journals (Sweden)

    T I Romantsova

    2013-03-01

    Full Text Available Aims. To study the dynamics of body weight, waist circumference, blood lipid and insulin demand in patients with type 2 diabetes mellitus (T2DM during first year of combined treatment with metformin and insulin analogues, compared with insulin analogue monotherapy.Materials and Methods. We examined 78 patients with T2DM on newly initiated insulin therapy, including 54 females and 24 males. Median age was 56 [51.0; 64.0] years, median disease duration – 9 [6.8;14.0] years. Participants were subdivided in two groups. First group was comprised of 48 subjects (33 females and 15 males, who received monotherapy with insulin analogues (glargine, de- temir, biphasic Aspart 30 and Humalog Mix 25 or rapid-acting lispro and aspart. Second group included 30 patients (18 females and12 males, who were treated with combined therapy (insulin analogues plus metformin. We measured HbA1c, plasma lipid composition, BMI, waist circumference and insulin demand initially and after one year of follow-up.Results. We showed that combined therapy vs. insulin monotherapy allows better glycemic compensation while reducing insulin demand and lowering risks for weight gain.Conclusions. Combined insulin analogue plus metformin treatment delivers better metabolic control in patients with T2DM and is as- sociated with lower risks for body weight gain and increase in insulin demand against monotherapy with insulin analogues.

  10. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

    Directory of Open Access Journals (Sweden)

    Zaman Ashraf

    Full Text Available A number of penicillin derivatives (4a-h were synthesized by the condensation of 6-amino penicillinic acid (6-APA with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

  11. In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors

    Directory of Open Access Journals (Sweden)

    Jae B. Park

    2017-12-01

    Full Text Available p38 Mitogen-activated protein kinase (p38 MAPK is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; −20 to −39 and several analogues with ΔE; −34 to −39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; −34 to −39 and in silico scores (Avg. score; −27.5 to −29.3. Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; −27.5 to −29.3 were found to inhibit p38 MAPK by 27–31% (p < 0.05 better than those with less scores (ΔE < −27.0. Especially, javamide-II-O-ethyl ester with relatively high in silico score (Avg. score; −29.2 inhibited p38 MAPK (IC50 = 9.9 μM a little better than its methyl ester with best in silico score (Avg. score; −29.3. To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22–73% (p < 0.05 in the differentiated THP-1 cells, and the inhibition was slightly stronger by the ethyl ester than the methyl ester. Altogether, this study suggests that javamide-II-O-ethyl ester may

  12. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina

    2007-01-01

    The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. Liraglutide is a glucagon-like peptide-1 receptor analogue, which is obtained by derivatising glucagon-like peptide-1 with a fatty acid, providing a compound with pharmacokinetic propert...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development....... properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...

  13. Efficient synthesis of 3,3-diheteroaromatic oxindole analogues and their in vitro evaluation for spermicidal potential.

    Science.gov (United States)

    Paira, Priyankar; Hazra, Abhijit; Kumar, Shrabanti; Paira, Rupankar; Sahu, Krishnendu B; Naskar, Subhendu; Saha, Pritam; Mondal, Shyamal; Maity, Arindam; Banerjee, Sukdeb; Mondal, Nirup B

    2009-08-15

    Syntheses of 3,3-diheteroaromatic oxindole derivatives has been achieved by coupling indole-2,3-dione (isatin) with differently substituted indoles and pyrrole in presence of I(2) in i-PrOH. The in vitro spermicidal potentials and the mode of spermicidal action of the synthesized analogues were evaluated and the derivative, 3,3-bis (5-methoxy-1H-indol-3-yl) indolin-2-one (3d) exhibited most significant activity.

  14. Electrooxidation potential as a tool in the early screening for new safer clozapine-like analogues

    NARCIS (Netherlands)

    Mouithys-Mickalad, A; Kauffmann, JM; Petit, C; Bruhwyler, J; Liao, Y; Wikstrom, H; Damas, J; Delarge, J; Deby-Dupont, G; Geczy, J; Liegeois, JF

    2001-01-01

    The chemical modification of clozapine (1) has permitted the finding of new analogues, e.g., olanzapine (2), quetiapine (3), 5-(4-methylpiperazin-1-yl)-8-chloropyrido[2,3-b] [1,5]benzoxazepine fumarate (9), with a clinical or psychopharmacological profile similar to that of clozapine. However, when

  15. Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence

    NARCIS (Netherlands)

    Bronsveld, H.K.; Braak, ter B.; Karlstad, O.; Vestergaard, P.; Starup-Linde, J.; Bazelier, M.T.; Bruin, de M.L.; Boer, de A.; Siezen, C.L.E.; Water, van de B.; van, der Laan J. W.; Schmidt, M.K.

    2015-01-01

    INTRODUCTION: Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms. METHOD: A

  16. Synthesis of new triazole arotinoids analogues via "Click Chemistry" with potential anticancer activity

    Directory of Open Access Journals (Sweden)

    Mariana A. A. Aleixo

    2012-06-01

    Full Text Available Retinoids are  a  class  of  natural  and  synthetic  vitamin A analogues structurally related to all-trans-retinoic acid (ATRA. This class of compounds can inhibit cell proliferation and induce differentiation and apoptosis of cells, and several are used in cancer therapy. Using the concept of bioisosterism, new triazole analogues were designed from the molecular modification of the potent derivative arotinoid AM580. This compound has an amide grouping which is a bioisostere of 1,2,3-triazole ring. Through "Click Chemistry” approach, triazole analogues were obtained by reaction of Huisgen 1,3-dipolar cycloaddition between aryl azides and terminal acetylene, previously synthesized. The reagents used were CuI, triethylamine and mixture of ethanol:water. The first compound synthesized showed anticancer activity, while the second proved to be inactive. The molecular docking results showed that both compounds have high affinity for the retinoid RARα receptor (related to anticancer activity, but probably the second compound has antagonist activity on this receptor.

  17. Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.

    Science.gov (United States)

    Houlihan, William J; Kelly, Lawrence; Pankuch, Jessica; Koletar, Judith; Brand, Leonard; Janowsky, Aaron; Kopajtic, Theresa A

    2002-09-12

    A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers.

  18. Design, synthesis and biological evaluation of novel peptide MC2 analogues from Momordica charantia as potential anti-diabetic agents.

    Science.gov (United States)

    Yang, Baowei; Li, Xue; Zhang, Chenyu; Yan, Sijia; Wei, Wei; Wang, Xuekun; Deng, Xin; Qian, Hai; Lin, Haiyan; Huang, Wenlong

    2015-04-21

    Three series of Momordica charantia (MC)2 analogues were designed, synthesized and evaluated for their anti-hyperglycaemic effects. Alanine scanning focusing on the peptide MC2 indicated the importance of the residues proline (Pro)(3), serine (Ser)(6), isoleucine (Ile)(7) and Ser(10) for anti-hyperglycaemic effects. Among the first series of MC2 analogues, peptide I-4 exhibited a better anti-hyperglycaemic effect and was chosen for further modification. A further two series of conformationally constrained analogues were designed by scanning the residues Pro(3), Ser(6), Ile(7), and Ser(10) with an i - (i + 2) lactam bridge consisting of a glutamic acid-Xaa-lysine (Glu-Xaa-Lys) scaffold and a diproline fragment. By screening in normal mice and mice with diabetes mellitus, peptides II-1, II-2 and III-3 showed a significant improvement in anti-hyperglycaemic and anti-oxidative activities compared with I-4. These data suggest that II-1, II-2 and III-3 could be candidates for future treatment of diabetes mellitus.

  19. Application of autoclaving-cooling cycling treatment to improve resistant starch content of corn-based rice analogues

    Science.gov (United States)

    Hidayat, B.; Muslihudin, M.; Akmal, S.

    2018-01-01

    Resistant starch is one important component determining the characteristics of a functional food. The aim of the research was to determine the cooling time optimum in the autoclaving-cooling treatment to increase the resistance starch content corn-based rice analogues, with 6 level of cooling time (0 hours/control, 12 hours, 24 hours, 36 hours, 48 hours and 60 hours). The results showed that cooling at 4°C for 60 hours would increase the resistant starch content (6.27% to 15.38%), dietary fiber content (14.53% to 20.17%); and decrease the digestible starch content (61.81% to 52.70%). Cooling time level at 4°C for 24 hours, would increase the sensory score of corn-based rice analogues then back down until cooling time level of 60 hours. Microscopic analysis of granular structure using SEM indicated that cooling time had a linear correlation with cracks intensity on the granule surface of the corn-based rice analogues. The high content of resistant starch showed that the application of cooling time level at 4°C for 24 hours would improve the functional properties of corn-based rice analogues with sensory characteristics remain favorable to panelists.

  20. Climate Analogues Suggest Limited Potential for Intensification of Production on Current Croplands Under Climate Change

    Science.gov (United States)

    Pugh, T. A. M.; Mueller, C.; Elliott, J.; Deryng, D.; Folberth, C.; Olin, S.; Schmid, E.; Arneth, A.

    2016-01-01

    Climate change could pose a major challenge to efforts towards strongly increase food production over the coming decades. However, model simulations of future climate-impacts on crop yields differ substantially in the magnitude and even direction of the projected change. Combining observations of current maximum-attainable yield with climate analogues, we provide a complementary method of assessing the effect of climate change on crop yields. Strong reductions in attainable yields of major cereal crops are found across a large fraction of current cropland by 2050. These areas are vulnerable to climate change and have greatly reduced opportunity for agricultural intensification. However, the total land area, including regions not currently used for crops, climatically suitable for high attainable yields of maize, wheat and rice is similar by 2050 to the present-day. Large shifts in land-use patterns and crop choice will likely be necessary to sustain production growth rates and keep pace with demand.

  1. Purine nucleoside analogues inhibit the repair of radiation-induced potentially lethal damage in mammalian cells in culture

    International Nuclear Information System (INIS)

    Nakatsugawa, S.; Kumar, A.

    1982-01-01

    Three purine nucleoside analogues were found to be much more effective than pyrimidine nucleoside analogues in the screening of PLD repair inhibitors using X-irradiated Chinese hamster HA-1 cells. Among the three purine nucleoside analogues, 3'-dG was the most effective at a non-toxic concentration. (author)

  2. Potential climatic mechanisms associated with the mega drought at 4200 cal yr BP: linking proxy data with modern climate analogues

    Science.gov (United States)

    Carter, V.; Shinker, J. J.

    2017-12-01

    Roughly 4200 years ago, a 150-year long mega drought occurred in the central Rocky Mountains, as indicated by pollen evidence from lake sediments from Long Lake, south-eastern Wyoming. However, pollen evidence does not record the climate mechanisms that caused the drought; they only provide evidence that the drought occurred. A modern climate analogue technique using North American Regional Reanalysis data was applied to the sedimentary data in order to identify possible synoptic and dynamic patterns that may have caused the mega drought at 4200 cal yr BP. Our results suggest warm and dry conditions were a result of anomalously higher-than-normal geopotential heights that were centred over the Great Plains beginning in the spring and persisting through the fall. Drought conditions during the growing seasons was the result of the anomalous high-pressure ridge, which suppressed moisture transport via the low level jet from the Gulf of Mexico, as well as brought in dry continental air from in the interior region of North America. The conditions associated with modern analogues offer a potential climate mechanism that caused the mega drought 4200 years ago, and likely led to the changes in vegetation composition as evidenced by the pollen record from Long Lake, Wyoming.

  3. Synthesis, antiproliferative, anti-tubulin activity, and docking study of new 1,2,4-triazoles as potential combretastatin analogues.

    Science.gov (United States)

    Mustafa, Muhamad; Abdelhamid, Dalia; Abdelhafez, ElShimaa M N; Ibrahim, Mahmoud A A; Gamal-Eldeen, Amira M; Aly, Omar M

    2017-12-01

    Combretastatin A4 (CA4) is a natural product characterized by a powerful inhibition of tubulin polymerization and a potential anticancer activity. However, therapeutic application of CA4 is substantially hindered due to geometric isomerization. In the current study, new cis-restricted Combretastatin A4 analogues containing 1,2,4-triazle in place of the olefinic bond were designed and synthesized. The synthesized compounds were evaluated for their in vitro antiproliferative activity in human hepatocellular carcinoma HepG2 and leukemia HL-60 cell lines using MTT assay. Moreover, fourteen compounds were selected and tested for their antiproliferative activity by the National Cancer Institute. Some of the tested compounds showed moderate activity against sixty cell lines. In vitro tubulin polymerization inhibitory activity was evaluated on HepG2 cells. The assay revealed that 6a showed a remarkable tubulin inhibition compared to CA4. Moreover, the cell cycle analysis revealed significant G2/M cell cycle arrest of the analogue 6c in HepG2 cells. Molecular docking combined with AMBER-based molecular mechanical minimization results showed several noncovalent interactions, including van der Waals and hydrogen-bonding with several amino acids within the colchicine binding site of β-subunit of tubulin. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Design of Two Alternative Routes for the Synthesis of Naftifine and Analogues as Potential Antifungal Agents

    Directory of Open Access Journals (Sweden)

    Rodrigo Abonia

    2018-02-01

    Full Text Available Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, the γ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5–7.8 µg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 µg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 µg/mL against C. neoformans.

  5. Design, synthesis, and biological evaluation of callophycin A and analogues as potential chemopreventive and anticancer agents.

    Science.gov (United States)

    Shen, Li; Park, Eun-Jung; Kondratyuk, Tamara P; Guendisch, Daniela; Marler, Laura; Pezzuto, John M; Wright, Anthony D; Sun, Dianqing

    2011-11-01

    Callophycin A was originally isolated from the red algae Callophycus oppositifolius and shown to mediate anticancer and cytotoxic effects. In our collaborative effort to identify potential chemopreventive and anticancer agents with enhanced potency and selectivity, we employed a tetrahydro-β-carboline-based template inspired by callophycin A for production of a chemical library. Utilizing a parallel synthetic approach, 50 various functionalized tetrahydro-β-carboline derivatives were prepared and assessed for activities related to cancer chemoprevention and cancer treatment: induction of quinone reductase 1 (QR1) and inhibition of aromatase, nitric oxide (NO) production, tumor necrosis factor (TNF)-α-induced NFκB activity, and MCF7 breast cancer cell proliferation. Biological results showed that the n-pentyl urea S-isomer 6a was the strongest inducer of QR1 with an induction ratio (IR) value of 4.9 at 50 μM [the concentration to double the activity (CD)=3.8 μM] and its corresponding R-isomer 6f had an IR value of 4.3 (CD=0.2 μM). The isobutyl carbamate derivative 3d with R stereochemistry demonstrated the most potent inhibitory activity of NFκB, with the half maximal inhibitory concentration (IC(50)) value of 4.8 μM, and also showed over 60% inhibition at 50 μM of NO production (IC(50)=2.8 μM). The R-isomer urea derivative 6j, having an appended adamantyl group, exhibited the most potent MCF7 cell proliferation inhibitory activity (IC(50)=14.7 μM). The S-isomer 12a of callophycin A showed the most potent activity in aromatase inhibition (IC(50)=10.5 μM). Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Pros and cons in endocrine practice: pre-surgical treatment with somatostatin analogues in acromegaly.

    Science.gov (United States)

    Losa, Marco; Bollerslev, Jens

    2016-06-01

    The aim of this commentary is to balance the pros and cons for pre-surgical SSA treatment in a modern perspective ending up with a pragmatic recommendation for treatment based on the current evidence and expertise of the authors. Even though prospective and randomized studies in this particular area are hampered by obvious limitations, the interpretation of the four published trials has in general been in favor of pre-treatment with SSA, showing a better outcome following surgery. However, major drawbacks of these studies, such as non-optimal diagnostic criteria for cure, potential selection bias, and timing of the postoperative evaluation in SSA pre-treated patients, limit their overall interpretation. Three matched-controlled studies showed remarkably similar results with no apparent beneficial effect of SSA pre-treatment on surgical outcome. Both prospective, randomized studies and retrospective studies did not find any significant difference in the rate of endocrine and non-endocrine complications related to surgery, despite the beneficial clinical effects of SSA treatment in most acromegalic patients. The newly diagnosed patient with acromegaly should be carefully evaluated in the trans-disciplinary neuroendocrine team and treatment individualized accordingly. The issue of SSA pre-treatment to improve surgical outcome is yet to be settled and further methodologically sound studies are probably necessary to clarify this point.

  7. On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B

    Science.gov (United States)

    Gao, Yu-Hua; Meng, Qing-Hua; Zhang, Zhan-Qing; Zhao, Ping; Shang, Qing-Hua; Yuan, Quan; Li, Yao; Deng, Juan; Li, Tong; Liu, Xue-En; Zhuang, Hui

    2016-01-01

    AIM To investigate potential predictors for treatment response to nucleos(t)ide analogues (NAs) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS Seventy-six HBeAg-positive CHB patients received 96-wk NAs optimized therapy (lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeAg, hepatitis B core antibody, hepatitis B virus (HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves (AUROC) of the independent predictors were calculated. RESULTS Forty-three CHB patients (56.6%) achieved virological response (VR: HBV DNA ≤ 300 copies/mL) and 15 patients (19.7%) developed HBeAg seroconversion (SC) after the 96-wk NAs treatment. The HBeAg level (OR = 0.45, P = 0.003) as well as its declined value (OR = 2.03, P = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBeAg titer 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeAg level (OR = 0.37, P = 0.013) as well as its declined value (OR = 2.02, P = 0.012) at 24-wk also independently predicted HBeAg SC, with the AUROC of 0.828 and 0.814, respectively. The HBeAg titer 2.2 lg PEIU/mL at 24-wk predicted HBeAg SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928. CONCLUSION The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy. PMID:28008342

  8. Chemistry of Renieramycins. 17. A New Generation of Renieramycins: Hydroquinone 5-O-Monoester Analogues of Renieramycin M as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells.

    Science.gov (United States)

    Chamni, Supakarn; Sirimangkalakitti, Natchanun; Chanvorachote, Pithi; Saito, Naoki; Suwanborirux, Khanit

    2017-05-26

    A series of hydroquinone 5-O-monoester analogues of renieramycin M were semisynthesized via bishydroquinonerenieramycin M (5) prepared from renieramycin M (1), a major cytotoxic bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. All 20 hydroquinone 5-O-monoester analogues possessed cytotoxicity with IC 50 values in nanomolar concentrations against the H292 and H460 human non-small-cell lung cancer (NSCLC) cell lines. The improved cytotoxicity toward the NSCLC cell lines was observed from the 5-O-monoester analogues such as 5-O-acetyl ester 6a and 5-O-propanoyl ester 7e, which exhibited 8- and 10-fold increased cytotoxicity toward the H292 NSCLC cell line (IC 50 3.0 and 2.3 nM, respectively), relative to 1 (IC 50 24 nM). Thus, the hydroquinone 5-O-monoester analogues are a new generation of the renieramycins to be further developed as potential marine-derived drug candidates for lung cancer treatment.

  9. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Barceló Carlos

    2005-12-01

    Full Text Available Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  10. Efficacy of peginterferon α-2a in treatment of chronic hepatitis B resistant to multiple nucleos(tide analogues

    Directory of Open Access Journals (Sweden)

    YANG Long

    2016-04-01

    Full Text Available ObjectiveTo investigate the efficacy of peginterferon alfa-2a (PEG-IFN α-2a in the treatment of HBeAg-positive chronic hepatitis B (CHB resistant to multiple nucleos(tide analogues (NAs. MethodsA total of 120 patients with HBeAg-positive CHB resistant to multiple nucleos(tide analogues who were hospitalized or treated in the outpatient department in our hospital from August 2009 to February 2014 were randomly divided into two groups, with 60 patients in each group. The patients in the treatment group stopped NAs and were given PEG-IFNα-2a for 48 weeks, and those in the control group received PEG-IFNα-2a for 48 weeks in addition to the original therapeutic regimen with NAs. The changes in the serological markers of hepatitis B and HBV DNA were observed at weeks 24 and 48 of treatment and at 24 weeks after drug discontinuation. The chi-square test was used for comparison of categorical data between groups, while comporison of continuous data was mode by t test. ResultsThe patients in both groups achieved a satisfactory outcome. The serum HBeAg clearance rate, HBeAg seroconversion rate, HBV DNA clearance rate, and HBsAg clearance rate showed no significant differences between the two groups at weeks 24 and 48 of treatment and at 24 weeks after treatment (all P>0.05. The adverse events that occurred during PEG-IFNα-2a treatment were pyrexia, headache, inflammation at the injection site, diarrhea, neutropenia, anemia, and depression, and the disease is not serious. ConclusionPEG-IFNα-2a is safe and effective in the treatment of CHB resistant to multiple NAs, and the patients can convert to PEG-IFNα-2a directly as their antiviral therapy.

  11. Deoxyfluoro-D-trehalose (FDTre) analogues as potential PET probes for imaging mycobacterial infection: rapid synthesis and purification, conformational analysis, and uptake by mycobacteria

    Science.gov (United States)

    Rundell, Sarah R.; Wagar, Zachary L.; Meints, Lisa M.; Olson, Claire D.; O’Neill, Mara K.; Piligian, Brent F.; Poston, Anne W.; Hood, Robin J.; Woodruff, Peter J.

    2016-01-01

    Mycobacterium tuberculosis, the etiological agent of human tuberculosis, requires the non-mammalian disaccharide trehalose for growth and virulence. Recently, detectable trehalose analogues have gained attention as probes for studying trehalose metabolism and as potential diagnostic imaging agents for mycobacterial infections. Of particular interest are deoxy-[18F]fluoro-D-trehalose (18F-FDTre) analogues, which have been suggested as possible positron emission tomography (PET) probes for in vivo imaging of M. tuberculosis infection. Here, we report progress toward this objective, including the synthesis and conformational analysis of four non-radioactive deoxy-[19F]fluoro-D-trehalose (19F-FDTre) analogues, as well as evaluation of their uptake by M. smegmatis. The rapid synthesis and purification of several 19F-FDTre analogues was accomplished in high yield using a one-step chemoenzymatic method. Conformational analysis of the 19F-FDTre analogues using NMR and molecular modeling methods showed that fluorine substitution had a negligible effect on the conformation of the native disaccharide, suggesting that fluorinated analogues may be successfully recognized and processed by trehalose metabolic machinery in mycobacteria. To test this hypothesis and to evaluate a possible route for delivery of FDTre probes specifically to mycobacteria, we showed that 19F-FDTre analogues are actively imported into M. smegmatis via the trehalose-specific transporter SugABC-LpqY. Finally, to demonstrate the applicability of these results to the efficient preparation and use of short-lived 18F-FDTre PET radiotracers, we carried out 19F-FDTre synthesis, purification, and administration to M. smegmatis in 1 hour. PMID:27560008

  12. Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term Treatment of Chronic Hepatitis B: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Abhasnee Sobhonslidsuk

    2016-01-01

    Full Text Available Background. There have been few reports of nucleotide analogue-related renal tubular dysfunction (RTD in CHB patients. We assessed the prevalence and presentation of nucleotide analogue-related proximal RTD. Methods. A cross-sectional study was performed in CHB patients taking nucleotide analogues. Inclusion criteria were patients who were on adefovir or tenofovir as mono- or add-on therapy with lamivudine (LAM >1 year. Serum and urine were collected. Fractional excretion of phosphate (FEPO4, uric acid (FEUA, and potassium was calculated. Renal losses were defined based on the criteria: protein (24-hour urine protein >150 mg, glucose (glycosuria with normoglycemia, phosphate (FEPO4 >18%, uric acid (FEUA >15%, potassium (renal potassium losses with hypokalemia, and bicarbonate (normal gap acidosis. Subclinical and overt proximal RTD were defined when 2 and ≥3 criteria presented. Results. Ninety-two patients were enrolled. The mean duration of nucleotide analogue taking was 55.1±29.6 months. Proximal RTD was found in 24 (26.1% patients (subclinical 15 (16.3% and overt 9 (9.8%. The severity of RTD was associated with the duration of nucleotide analogue (P=0.01. Conclusions. The prevalence of proximal RTD in CHB patients taking nucleotide analogues was 26%. The severity of RTD was associated with the treatment duration. Comprehensive testing is necessary for early detecting nucleotide analogue-related nephrotoxicity.

  13. An Indomethacin Analogue, N-(4-Chlorobenzoyl)-melatonin, is a Selective Inhibitor of Aldo-keto Reductase 1C3 (Type 2 3α-HSD, Type 5 17β-HSD, and Prostaglandin F Synthase), a Potential Target for the Treatment of Hormone Dependent and Hormone Independent Malignancies

    Science.gov (United States)

    Byrns, Michael C.; Steckelbroeck, Stephan; Penning, Trevor M.

    2008-01-01

    Aldo-keto reductase (AKR) 1C3 (type 2 3α-HSD, type 5 17β-HSD, and prostaglandin F synthase) regulates ligand access to steroid hormone and prostaglandin receptors and may stimulate proliferation of prostate and breast cancer cells. NSAIDs are known inhibitors of AKR1C enzymes. An NSAID analogue that inhibits AKR1C3 but is inactive against the cyclooxygenases and the other AKR1C family members would provide an important tool to examine the role of AKR1C3 in proliferative signaling. We tested NSAIDs and NSAID analogues for inhibition of the reduction of 9,10-phenanthrenequinone (PQ) catalyzed by AKR1C3 and the closely related isoforms AKR1C1 and AKR1C2. Two of the compounds initially screened, indomethacin and its methyl ester, were specific for AKR1C3 versus the other AKR1C isoforms. Based on these results and the crystal structure of AKR1C3, we predicted that N-(4-chlorobenzoyl)-melatonin (CBM), an indomethacin analogue that does not inhibit the cyclooxygenases, would selectively inhibit AKR1C3. CBM inhibited the reduction of PQ by AKR1C3, but did not significantly inhibit AKR1C1 or AKR1C2. Indomethacin and CBM also inhibited the AKR1C3-catalyzed reduction of Δ4-androstene-3,17-dione but did not significantly inhibit the reduction of steroid hormones catalyzed by AKR1C1 or AKR1C2. The pattern of inhibition of AKR1C3 by indomethacin and CBM was uncompetitive versus PQ, but competitive versus Δ4-androstene-3,17-dione, indicating that two different inhibitory complexes form during the ordered bi-bi reactions. The identification of CBM as a specific inhibitor of AKR1C3 will aid the investigation of its roles in steroid hormone and prostaglandin signaling and the resultant effects on cancer development. PMID:17950253

  14. An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies.

    Science.gov (United States)

    Byrns, Michael C; Steckelbroeck, Stephan; Penning, Trevor M

    2008-01-15

    Aldo-keto reductase (AKR) 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase) regulates ligand access to steroid hormone and prostaglandin receptors and may stimulate proliferation of prostate and breast cancer cells. NSAIDs are known inhibitors of AKR1C enzymes. An NSAID analogue that inhibits AKR1C3 but is inactive against the cyclooxygenases and the other AKR1C family members would provide an important tool to examine the role of AKR1C3 in proliferative signaling. We tested NSAIDs and NSAID analogues for inhibition of the reduction of 9,10-phenanthrenequinone (PQ) catalyzed by AKR1C3 and the closely related isoforms AKR1C1 and AKR1C2. Two of the compounds initially screened, indomethacin and its methyl ester, were specific for AKR1C3 versus the other AKR1C isoforms. Based on these results and the crystal structure of AKR1C3, we predicted that N-(4-chlorobenzoyl)-melatonin (CBM), an indomethacin analogue that does not inhibit the cyclooxygenases, would selectively inhibit AKR1C3. CBM inhibited the reduction of PQ by AKR1C3, but did not significantly inhibit AKR1C1 or AKR1C2. Indomethacin and CBM also inhibited the AKR1C3-catalyzed reduction of Delta(4)-androstene-3,17-dione but did not significantly inhibit the reduction of steroid hormones catalyzed by AKR1C1 or AKR1C2. The pattern of inhibition of AKR1C3 by indomethacin and CBM was uncompetitive versus PQ, but competitive versus Delta(4)-androstene-3,17-dione, indicating that two different inhibitory complexes form during the ordered bi bi reactions. The identification of CBM as a specific inhibitor of AKR1C3 will aid the investigation of its roles in steroid hormone and prostaglandin signaling and the resultant effects on cancer development.

  15. Electronic structure and vibrational spectra of cis-diammine(orotato)platinum(II), a potential cisplatin analogue: DFT and experimental study

    Science.gov (United States)

    Wysokiński, Rafał; Hernik, Katarzyna; Szostak, Roman; Michalska, Danuta

    2007-03-01

    Orotic acid (vitamin B 13) is a key intermediate in biosynthesis of the pyrimidine nucleotides in living organisms, moreover, it may serve as the biological carrier for some metal ions. cis-Diammine(orotato)platinum(II), cis-[Pt(C 5H 2N 2O 4)(NH 3) 2] can be considered as a new potential cisplatin analogue. The FT-Raman and FT-IR spectra of the title complex are reported, for the first time. The molecular structure, vibrational frequencies, and the theoretical infrared and Raman intensities have been calculated by the density functional mPW1PW91 method. The detailed vibrational assignment has been made on the basis of the calculated potential energy distribution. The theoretically predicted IR and Raman spectra show very good agreement with experiment. Natural bond orbital (NBO) analyses were performed for cisplatin, carboplatin and the title complex. The results provided new data on the nature of platinum-ligand bonding in these compounds. Strong intramolecular hydrogen bond between the orotate ligand and the coordinated ammonia group stabilizes the structure of the platinum(II) complex. Thus, it is suggested that the orotate ligand in the title complex is more inert to the substitution reactions than the chloride ligands in cisplatin.

  16. Electronic structure and vibrational spectra of cis-diammine(orotato)platinum(II), a potential cisplatin analogue: DFT and experimental study

    International Nuclear Information System (INIS)

    Wysokinski, Rafal; Hernik, Katarzyna; Szostak, Roman; Michalska, Danuta

    2007-01-01

    Orotic acid (vitamin B 13 ) is a key intermediate in biosynthesis of the pyrimidine nucleotides in living organisms, moreover, it may serve as the biological carrier for some metal ions. cis-Diammine(orotato)platinum(II), cis-[Pt(C 5 H 2 N 2 O 4 )(NH 3 ) 2 ] can be considered as a new potential cisplatin analogue. The FT-Raman and FT-IR spectra of the title complex are reported, for the first time. The molecular structure, vibrational frequencies, and the theoretical infrared and Raman intensities have been calculated by the density functional mPW1PW91 method. The detailed vibrational assignment has been made on the basis of the calculated potential energy distribution. The theoretically predicted IR and Raman spectra show very good agreement with experiment. Natural bond orbital (NBO) analyses were performed for cisplatin, carboplatin and the title complex. The results provided new data on the nature of platinum-ligand bonding in these compounds. Strong intramolecular hydrogen bond between the orotate ligand and the coordinated ammonia group stabilizes the structure of the platinum(II) complex. Thus, it is suggested that the orotate ligand in the title complex is more inert to the substitution reactions than the chloride ligands in cisplatin

  17. Electronic structure and vibrational spectra of cis-diammine(orotato)platinum(II), a potential cisplatin analogue: DFT and experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Wysokinski, Rafal; Hernik, Katarzyna [Faculty of Chemistry, Wroclaw University of Technology, Smoluchowskiego 23, 50-370 Wroclaw (Poland); Szostak, Roman [Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw (Poland); Michalska, Danuta [Faculty of Chemistry, Wroclaw University of Technology, Smoluchowskiego 23, 50-370 Wroclaw (Poland)], E-mail: danuta.michalska@pwr.wroc.pl

    2007-03-06

    Orotic acid (vitamin B{sub 13}) is a key intermediate in biosynthesis of the pyrimidine nucleotides in living organisms, moreover, it may serve as the biological carrier for some metal ions. cis-Diammine(orotato)platinum(II), cis-[Pt(C{sub 5}H{sub 2}N{sub 2}O{sub 4})(NH{sub 3}){sub 2}] can be considered as a new potential cisplatin analogue. The FT-Raman and FT-IR spectra of the title complex are reported, for the first time. The molecular structure, vibrational frequencies, and the theoretical infrared and Raman intensities have been calculated by the density functional mPW1PW91 method. The detailed vibrational assignment has been made on the basis of the calculated potential energy distribution. The theoretically predicted IR and Raman spectra show very good agreement with experiment. Natural bond orbital (NBO) analyses were performed for cisplatin, carboplatin and the title complex. The results provided new data on the nature of platinum-ligand bonding in these compounds. Strong intramolecular hydrogen bond between the orotate ligand and the coordinated ammonia group stabilizes the structure of the platinum(II) complex. Thus, it is suggested that the orotate ligand in the title complex is more inert to the substitution reactions than the chloride ligands in cisplatin.

  18. Potential cerebral perfusion agents: synthesis and evaluation of a radioiodinated vinylalkylbarbituric acid analogue

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, P.C.; Callahan, A.P.; Cunningham, E.B.; Knapp, F.F. Jr.

    1983-05-01

    A new iodinated barbiturate has been prepared. Treatment of 5-chloropentyne and propargyl bromide with diethyl 2-ethyl-2-sodiomalonate (DESM) provided diethyl 2-ethyl-2-(1-pentyn-5-yl)malonate (3) and diethyl 2-ethyl-2-propargylmalonate (4), respectively. Similar condensation of DESM with (E)-(5-iodo-1-penten-1-yl)boronic acid (9) or the reaction of catecholborane with 3 provided diethyl (E)-2-ethyl-2-(1-borono-1-penten-5-yl)malonate (8). The direct sodium iodide-chloramine-T iodination of 8 or the treatment of (E)-1,5-diiodo-1-pentene (10) with DESM provided diethyl (E)-2-ethyl-2-(1-iodo-1-penten-5-yl)malonate (11). The condensation of functionalized malonates 3, 4, and 11 with urea in the presence of a base provided the corresponding barbiturates, 5-ethyl-5-(1-pentyn-5-yl)-(5), 5-ethyl-5-propargyl- (6), and (E)-5-ethyl-5-(1-iodo-1-penten-5-yl)barbituric acid (12), respectively. (E)-6-(Ethoxycarbonyl)-1-iodo-1-octene-6-carboxylic acid (13) was isolated as the hydrolytic byproduct of 11. Compound 13 decarboxylated under vacuum to provide ethyl (E)-1-iodo-1-octene-6-carboxylate (14). The /sup 125/I-labeled congeners of 12 and 13 were synthesized in the same manner and evaluated in rats. The barbiturate 12 exhibited significant brain uptake (approximately 1% dose after 5 min), demonstrating that iodinated barbiturates freely cross the intact blood-brain barrier.

  19. In vitro study on potential pharmacological activity of curcumin analogues and their copper complexes.

    Science.gov (United States)

    Ferrari, Erika; Benassi, Rois; Saladini, Monica; Orteca, Giulia; Gazova, Zuzana; Siposova, Katarina

    2017-03-01

    Curcumin and its derivatives have attracted great interest in the prevention and treatment of Alzheimer's disease, thanks both to the ability to hinder the formation of amyloid-beta (Aβ) aggregates and the ability to bind Cu (II) ion. In this article, we explore the ability of curcumin derivatives of K2T series to affect amyloid Aβ 1-40 aggregation. These derivatives were obtained by introducing the t-butyl ester group through a methylenic spacer on the central carbon atom of the β-diketo moiety of curcumin frame. The studied curcuminoids were demonstrated to inhibit Aβ 1-40 fibrillization at substoichiometric concentrations with IC 50 value near that of curcumin. In addition, the antioxidant properties and DNA interaction of their Cu(II) complexes is evaluated. The structure of Cu(II)-K2T31 complex is also proposed on the basis of DFT calculation. © 2016 John Wiley & Sons A/S.

  20. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Carlos Barceló

    2011-05-01

    Full Text Available Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  1. Neoechinulin B and its analogues as potential entry inhibitors of influenza viruses, targeting viral hemagglutinin.

    Science.gov (United States)

    Chen, Xueqing; Si, Longlong; Liu, Dong; Proksch, Peter; Zhang, Lihe; Zhou, Demin; Lin, Wenhan

    2015-03-26

    A class of prenylated indole diketopiperazine alkaloids including 15 new compounds namely rubrumlines A-O obtained from marine-derived fungus Eurotium rubrum, were tested against influenza A/WSN/33 virus. Neoechinulin B (18) exerted potent inhibition against H1N1 virus infected in MDCK cells, and is able to inhibit a panel of influenza virus strains including amantadine- and oseltamivir-resistant clinical isolates. Mechanism of action studies indicated that neoechinulin B binds to influenza envelope hemagglutinin, disrupting its interaction with the sialic acid receptor and the attachment of viruses to host cells. In addition, neoechinulin B was still efficient in inhibiting influenza A/WSN/33 virus propagation even after a fifth passage. The high potency and broad-spectrum activities against influenza viruses with less drug resistance make neoechinulin B as a new lead for the development of potential inhibitor of influenza viruses. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Benzo- and cyclohexanomazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.

    Science.gov (United States)

    Houlihan, William J; Ahmad, Umer F; Koletar, Judith; Kelly, Lawrence; Brand, Leonard; Kopajtic, Theresa A

    2002-09-12

    A series of mazindol (1), homomazindol (2), and bishomomazindol (3) derivatives with a benzo or cyclohexano ring fused at various sites were prepared as part of an SAR study to determine the effect of increased aliphatic and aromatic lipophilicity on selected in vitro assays used to identify potential cocaine-like and cocaine antagonism activity. Very good (IC(50) = 2-3 nM) inhibition of [(3)H] WIN 35,428 and [(125)I] RTI-55 binding on rat or guinea pig striatal membranes and HEK cells expressing cDNA for the human dopamine transporter (HEK-hDAT) was shown by the 8,9-benzomazindol 25 and 9,10-benzohomomazindol 28. All new compounds were weaker inhibitors of [(3)H] DA uptake in HEK-hDAT cells than 1 and 2. No improvement in the binding selectivity ratio (SERT/DAT and NET/DAT) was found when compared to 2. Compounds 25and 28 showed a considerable increase versus 1 in uptake/binding discrimination ratios at the DAT (311.0 and 182.1 vs 0.9), SERT (33.6 and 127.3 vs 1.9), and NET (7.3 and 10.0 vs 0.3).

  3. Infrastructure and mechanical properties of a fault zone in sandstone as an outcrop analogue of a potential geothermal reservoir

    Science.gov (United States)

    Bauer, J. F.; Meier, S.; Philipp, S. L.

    2013-12-01

    Due to high drilling costs of geothermal projects, it is economically sensible to assess the potential suitability of a reservoir prior to drilling. Fault zones are of particular importance, because they may enhance fluid flow, or be flow barriers, respectively, depending on their particular infrastructure. Outcrop analogue studies are useful to analyze the fault zone infrastructure and thereby increase the predictability of fluid flow behavior across fault zones in the corresponding deep reservoir. The main aims of the present study are to 1) analyze the infrastructure and the differences of fracture system parameters in fault zones and 2) determine the mechanical properties of the faulted rocks. We measure fracture frequencies as well as orientations, lengths and apertures and take representative rock samples for each facies to obtain Young's modulus, compressive and tensile strengths in the laboratory. Since fractures reduce the stiffnesses of in situ rock masses we use an inverse correlation of the number of discontinuities to calculate effective (in situ) Young's moduli to investigate the variation of mechanical properties in fault zones. In addition we determine the rebound hardness, which correlates with the compressive strength measured in the laboratory, with a 'Schmidt-Hammer' in the field because this allows detailed maps of mechanical property variations within fault zones. Here we present the first results for a fault zone in the Triassic Lower Bunter of the Upper Rhine Graben in France. The outcrop at Cleebourg exposes the damage zone of the footwall and a clear developed fault core of a NNW-SSE-striking normal fault. The approximately 15 m wide fault core consists of fault gouge, slip zones, deformation bands and host rock lenses. Intensive deformation close to the core led to the formation of a distal fault core, a 5 m wide zone with disturbed layering and high fracture frequency. The damage zone also contains more fractures than the host rock

  4. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents

    Science.gov (United States)

    Corcoran, Aoife; Nadkarni, Sharmin; Yasuda, Kaori; Sakaki, Toshiyuki; Brown, Geoffrey; Kutner, Andrzej; Marcinkowska, Ewa

    2016-01-01

    Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist. PMID:26840307

  5. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents

    Directory of Open Access Journals (Sweden)

    Aoife Corcoran

    2016-02-01

    Full Text Available Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2 were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1 were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734 contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734. However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733 or more (52% for PRI-1732 resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist.

  6. Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence

    DEFF Research Database (Denmark)

    Bronsveld, Heleen K; ter Braak, Bas; Karlstad, Øystein

    2015-01-01

    , the pooled analysis of 13 epidemiological studies did not show evidence for an association between insulin glargine treatment and an increased breast cancer risk (HR 1.04; 95 % CI 0.91-1.17; p=0.49) versus no glargine in patients with diabetes mellitus. It has to be taken into account that the number......INTRODUCTION: Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms. METHOD......: A systematic literature search was performed on breast cell-line, animal and human studies using the key words 'insulin analogue' and 'breast neoplasia' in MEDLINE at PubMed, EMBASE, and ISI Web of Science databases. A quantitative and qualitative review was performed on the epidemiological data; due...

  7. The potential of natural analogues in assessing systems for deep disposal of high-level radioactive waste

    International Nuclear Information System (INIS)

    Chapman, N.A.; McKinley, I.G.; Smellie, J.A.T.

    1984-08-01

    Many of the processes which will lead to the breakdown of engineered barriers and the mobilization of radionuclides in a deep waste repository have analogies in natural geological systems. These 'natural analogues' are seen as a particularly important means of validating predictive models, under the broad heading of radionuclide migration, which are used in long-term safety analyses. Their principal value is the opportunity they provide to examine processes occurring over geological timescales, hence allowing more confident extrapolation of short timescales experimental data. This report begins by reviewing the processes leading to breakdown of containment in a high-level radioactive waste repository in crystalline bedrock and the subsequent migration mechanisms for radionuclides back to the biosphere. Nine specific processes are identified as being of the most significance in migration models, based on available sensitivity analyses. These processes are considered separately in detail, reviewing first the mechanisms involved and the most important unknown then the types of natural analogue which could most usefully provide supporting evidence for the effects of the process. Conclusions are drawn, for each process as to the extent to which analogues validate current predictions on scale and effect, longevity of function, etc. Where possible, quantitative evaluations are given, derived from analogue studies. A summary is provided of the conclusions for each process, and the most important topics for further studies are listed. Specific examples of these requisite analogues are given. The report emphasises throughout the importance of linking analogues to well defined processes, concluding that analogues of complete disposal systems do not exist. The results are seen to be widely applicable. A considerable amount of the information reviewed and presented could be used in the assessment of disposal of other waste types in other host rocks. (Author)

  8. GRISEOFULVIN ANALOGUES FOR THE TREATMENT OF CANCER BY INHIBITION OF CENTROSOMAL CLUSTERING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to uses of compounds having a structure as shown by formula (I) for the manufacture of a pharmaceutical composition for the treatment of cancer. Moreover, the present invention encompasses methods of treatment for said diseases....

  9. Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment

    Directory of Open Access Journals (Sweden)

    Larrick James W

    2009-07-01

    Full Text Available Abstract Background While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1. The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated. Methods In alloxan-treated mice (a model of type 1 diabetes, drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-κB activation induced by IL-1β and IFN-γ was investigated. Results In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4 membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-κB activation. Conclusion We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-κB inhibitory activity. AL-1 is a potential new anti-diabetic agent.

  10. GRISEOFULVIN ANALOGUES FOR THE TREATMENT OF CANCER BY INHIBITION OF CENTROSOMAL CLUSTERING

    DEFF Research Database (Denmark)

    2010-01-01

    The invention relates to compounds of the formula (I), where the symbols have the meaning given in the specification, for use in a method for treating cancer, to use of these compounds for the manufacture of a pharmaceutical composition for the treatment of cancer, and to methods of treatment for...

  11. Methemoglobinemia hemotoxicity of some antimalarial 8-aminoquinoline analogues and their hydroxylated derivatives: density functional theory computation of ionization potentials

    Science.gov (United States)

    The administration of primaquine (PQ), an essential drug for treatment and radical cure of malaria, can lead to methemoglobin formation and life-threatening hemolysis for glucose-6-phosphate dehydrogenase deficient patients. The ionization potential (IP, a quantitative measure of the ability to lose...

  12. 3D modelling of a dolomitized syn-sedimentary structure: an exhumed potential analogue of hydrocarbon reservoir.

    Science.gov (United States)

    Martinelli, Mattia; Franceschi, Marco; Massironi, Matteo; Bistacchi, Andrea; Di Cuia, Raffaele; Rizzi, Alessandro

    2016-04-01

    The decrease in discoveries of new hydrocarbon reservoirs has twofold implications: i) the need to improve our knowledge of classic reservoirs, such as traps within extensional syn-sedimentary structures, and ii) enhanced efforts aimed at better understanding complex type of reservoirs. In particular, in the last few years, fault related dolomitized bodies, often associated to extensional faults, received worldwide attention thanks to the capability of dolomitizing fluids to improve the pore network. However, the shape and geometries of the dolomitized bodies within complex fault network as well as the related porosity distribution and evolution is difficult to predict. The study of outcrop analogues can help to solve these issues. In this work, we focused our attention on the Early Jurassic carbonate sediments of the Calcari Grigi Group deposited on the Trento Platform (Italian Southern Alps). The stratigraphic succession encompasses (from bottom to top): the peritidal limestones of the Monte Zugna Formation, the initially highly porous Loppio Oolitic Limestone and the nearly tight marls and marly limestones of the lower Rotzo Formation. During Early Jurassic, after the deposition of the Loppio Oolitic Limestone, the Trento Platform underwent syn-sedimentary extensional tectonics, which caused the formation of numerous tilted blocks. Differential subsidence of these blocks is testified by abrupt thickness changes in Rotzo Formation. This created a structural framework favourable to the formation of syn-sedimentary extensional traps (with the Loppio Oolitic Limestone as reservoir and Rotzo Formation as seal). In the Tertiary, Alpine compressional tectonics caused the reactivation of the Jurassic faults with a strike slip kinematics and was associated with the circulation of dolomitizing fluids. The combination of these events led to the formation of secondary fault-related dolomitized bodies. The enhanced pore network in correspondence of the dolomitized dykes

  13. BALANOL ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid...

  14. Recent advances in understanding the characteristics of seismogenic intraplate deformation in Australia, and the potential for using global analogues

    Science.gov (United States)

    Clark, Dan; McPherson, Andrew

    2017-04-01

    relation to individual faults in non-cratonic and extended superdomains. However, large earthquake recurrence and slip are demonstrably not evenly distributed in time. Within the limitations of the sparse paleoseismological data, temporal clustering of large events appears to be a common (perhaps ubiquitous?) characteristic. Over the last few decades, permanent and campaign GPS studies have failed to detect a tectonic deformation signal from which a strain budget could be calculated. Recent studies have used these observations, amongst others, to propose an orders of magnitude difference in the timescales of strain accumulation and seismogenic strain release in intraplate environments - i.e. clusters of large events deplete long-lived pools of lithospheric strain. The recognition of a relationship between crustal type/lithospheric thickness and seismogenic potential in Australia provides a framework for assessing whether ergodic substitution (i.e. global analogue studies) might be warranted as a tool to better understand intraplate seismicity worldwide. Further research is required to assess how variation in crustal stress regime may influence faulting characteristics within different superdomains.

  15. Synthesis, Characterization and In Vitro Anticancer Activity of C-5 Curcumin Analogues with Potential to Inhibit TNF-α-Induced NF-κB Activation

    Directory of Open Access Journals (Sweden)

    Amit Anthwal

    2014-01-01

    Full Text Available In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5 and colon cancer (HCT116 cell lines. Further, these compounds were found to have better potential to inhibit TNF-α-induced NF-κB activation in comparison to curcumin, which show their potential to act as anti-inflammatory agents. Some compounds were found to show higher cytotoxicity against cancer cell lines in comparison to curcumin used as standard.

  16. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina

    2007-01-01

    properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development....

  17. Basal insulin analogues in the treatment of diabetes mellitus: What progress have we made?

    OpenAIRE

    Kalra, Sanjay

    2015-01-01

    Over the past few decades, continuous progress has been made in the development of insulin therapy. Basal insulins were developed around 60 years ago. However, existing basal insulins were found to have limitations. An ideal basal insulin should have the following properties viz. longer duration of action, a flat time-action profile, low day-to-day glycaemic variability, and the potential for flexible dosing. Basal insulins have advanced over the years, from lectin and neutral protamine Haged...

  18. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model.

    Directory of Open Access Journals (Sweden)

    Vadivel Parthsarathy

    Full Text Available Neurogenesis is a life long process, but the rate of cell proliferation and differentiation decreases with age. In Alzheimer's patients, along with age, the presence of Aβ in the brain inhibits this process by reducing stem cell proliferation and cell differentiation. GLP-1 is a growth factor that has neuroprotective properties. GLP1 receptors are present on neuronal progenitor cells, and the GLP-1 analogue liraglutide has been shown to increase cell proliferation in an Alzheimer's disease (AD mouse model. Here we investigated acute and chronic effects of liraglutide on progenitor cell proliferation, neuroblast differentiation and their subsequent differentiation into neurons in wild type and APP/PS-1 mice at different ages. APP/PS1 and their littermate controls, aged 3, 6, 12, 15 months were injected acutely or chronically with 25 nmol/kg liraglutide. Acute treatment with liraglutide showed an increase in cell proliferation in APP/PS1 mice, but not in controls whereas chronic treatment increased cell proliferation at all ages (BrdU and Ki67 markers. Moreover, numbers of immature neurons (DCX were increased in both acute and chronic treated animals at all ages. Most newly generated cells differentiated into mature neurons (NeuN marker. A significant increase was observed with chronically treated 6, 12, 15 month APP/PS1 and WT groups. These results demonstrate that liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza(TM, increases neurogenesis, which may have beneficial effects in neurodegenerative disorders like AD.

  19. Basal insulin analogues in the treatment of diabetes mellitus: What progress have we made?

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available Over the past few decades, continuous progress has been made in the development of insulin therapy. Basal insulins were developed around 60 years ago. However, existing basal insulins were found to have limitations. An ideal basal insulin should have the following properties viz. longer duration of action, a flat time-action profile, low day-to-day glycaemic variability, and the potential for flexible dosing. Basal insulins have advanced over the years, from lectin and neutral protamine Hagedorn to the currently available insulin degludec. Currently, the focus is on developing a basal insulin that can give coverage for the entire day, with lesser variability and flexible administration. Insulin degludec has been a significant leap in that direction. In addition, U300 insulin glargine and pegylated lispro represent further developments in basal insulin pharmacotherapeutics.

  20. Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo

    Science.gov (United States)

    Batista, Denise da Gama Jaén; Batista, Marcos Meuser; de Oliveira, Gabriel Melo; Britto, Constança Carvalho; Rodrigues, Ana Carolina Mondaine; Stephens, Chad E.; Boykin, David W.; Soeiro, Maria de Nazaré Correia

    2011-01-01

    Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via ip route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals. PMID:21814568

  1. The effects of nucleoside analogue prophylactic treatment on HBV activation in HBcAb+ patients undergoing immunosuppressive therapy.

    Science.gov (United States)

    Liu, H-L; Zhao, Z; Yang, H; Liu, F-F; Liu, Q; Luo, Q; Yuan, Q; Chen, L-M; Zeng, A-Z

    2013-09-01

    We investigated the effects of prophylactic nucleoside analogue treatment on HBV activation in patients with antibodies against core antigen (HBcAb+) patients undergoing immunosuppressive therapy. Patients (113), who were HBcAb+, with various autoimmune diseases, undergoing immunosuppressive therapy, were divided into two groups. The control group, not treated with antivirals, and the prophylactic group, treated with antiviral drugs. The two groups were evaluated for changes in serum biochemical marker (alanine aminotransferase ALT), virological marker (HBV DNA) and for seroconversion. In the control group, the number of patients with an increase in ALT in patients with isolated HBcAb and HBcAb and antibodies against HBsAg (HBsAb +) were five (20.0%) and one (2.8%), respectively (P HBcAb+ subgroup and one case (2.8%) in HBsAb+/HBcAb+ subgroup (P HBcAb+ only population, six patients (24.0%) in the control group had an increase in HBV DNA compared with none in the antiviral prophylactic group (P HBcAb+ in the control group underwent an HBsAg seroconversion when receiving immunosuppressive therapy for 18 months, while none in the antiviral prophylactic group underwent reversion to HBsAg positivity (P = 0.4949). Under immunosuppressive condition, the risk of HBV activation was much higher in patients with HBcAb than in patients with both HBcAb and antibodies to HBsAb group. Antiviral prophylactic therapy could significantly reduce the risk of HBV reactivation. © 2013 John Wiley & Sons Ltd.

  2. Chemoenzymatic preparation of germacrene analogues.

    Science.gov (United States)

    Cascón, Oscar; Touchet, Sabrina; Miller, David J; Gonzalez, Veronica; Faraldos, Juan A; Allemann, Rudolf K

    2012-10-09

    A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies.

  3. Chemoenzymatic preparation of germacrene analogues

    OpenAIRE

    Cascón, Oscar; Touchet, Sabrina; Miller, David James; Gonzalez, Veronica; Faraldos, Juan A.; Allemann, Rudolf Konrad

    2012-01-01

    A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies.

  4. The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    Lewies Angélique

    2015-08-01

    Full Text Available Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs are caused by a variety of pathogens and are particularly wide-spread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated.

  5. Potential targets for the treatment of preeclampsia.

    Science.gov (United States)

    Oyston, Charlotte J; Stanley, Joanna L; Baker, Philip N

    2015-01-01

    Preeclampsia is a disorder of pregnancy, typically characterized by hypertension and proteinuria observed after the 20th week of gestation. Preeclampsia has dire consequences for both maternal and neonatal health: it is associated with 50,000 - 100,000 annual deaths globally, as well as serious fetal and neonatal morbidity and mortality, including increased risk of fetal growth restriction and still birth. Despite the severe health, social, and economic costs of preeclampsia, currently the only curative therapy is delivery of the baby and placenta, which itself carries the associated risks of premature birth. The lack of treatments for this condition is attributable to a number of causes, including but not limited to: a partial understanding of the complex pathophysiological mechanisms underlying this complex disease; an inability to sensitively predict women who will go on to develop the disease; and a paucity of robust animal models with which to test new treatments. Recently, progress has been made in identifying potential new therapeutic targets. This review will discuss in detail the evidence supporting further investigation of these targets, which include angiogenic factors, agents that increase vasodilation, anti-inflammatory drugs, substances that reduce oxidative stress, and statins. New therapeutic targets have the potential to make a significant positive impact on maternal and neonatal health. It is exciting that a number of potential therapies are currently being investigated; however, it is also vital that basic research continues to identify potential mechanisms and targets, and that any potential therapy is thoroughly tested before progression to clinical trial.

  6. Natural Analogue Synthesis Report

    Energy Technology Data Exchange (ETDEWEB)

    A. M. Simmons

    2002-05-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport

  7. NATURAL ANALOGUE SYNTHESIS REPORT

    International Nuclear Information System (INIS)

    Simmons, A.M.

    2004-01-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature along with results of quantitative studies conducted specifically for the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement-drift degradation, waste-form degradation, waste-package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated-zone (SZ) transport, impact of radionuclide release on the biosphere

  8. A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases

    Science.gov (United States)

    Rashid, M. Harunur; Huq, Redwan; Tanner, Mark R.; Chhabra, Sandeep; Khoo, Keith K.; Estrada, Rosendo; Dhawan, Vikas; Chauhan, Satendra; Pennington, Michael W.; Beeton, Christine; Kuyucak, Serdar; Norton, Raymond S.

    2014-03-01

    HsTX1 toxin, from the scorpion Heterometrus spinnifer, is a 34-residue, C-terminally amidated peptide cross-linked by four disulfide bridges. Here we describe new HsTX1 analogues with an Ala, Phe, Val or Abu substitution at position 14. Complexes of HsTX1 with the voltage-gated potassium channels Kv1.3 and Kv1.1 were created using docking and molecular dynamics simulations, then umbrella sampling simulations were performed to construct the potential of mean force (PMF) of the ligand and calculate the corresponding binding free energy for the most stable configuration. The PMF method predicted that the R14A mutation in HsTX1 would yield a > 2 kcal/mol gain for the Kv1.3/Kv1.1 selectivity free energy relative to the wild-type peptide. Functional assays confirmed the predicted selectivity gain for HsTX1[R14A] and HsTX1[R14Abu], with an affinity for Kv1.3 in the low picomolar range and a selectivity of more than 2,000-fold for Kv1.3 over Kv1.1. This remarkable potency and selectivity for Kv1.3, which is significantly up-regulated in activated effector memory cells in humans, suggest that these analogues represent valuable leads in the development of therapeutics for autoimmune diseases.

  9. Synthesis and biological evaluation of quinoline analogues of flavones as potential anticancer agents and tubulin polymerization inhibitors.

    Science.gov (United States)

    Shobeiri, Nikta; Rashedi, Maryam; Mosaffa, Fatemeh; Zarghi, Afshin; Ghandadi, Morteza; Ghasemi, Ali; Ghodsi, Razieh

    2016-05-23

    A new series of 2-aryl-trimethoxyquinoline analogues was designed and synthesized as tubulin inhibitors using methoxylated flavones as the lead compounds. The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including MCF-7, MCF-7/MX, A-2780, and A-2780/RCIS. All the alcoholic derivatives (6a-6e) showed significant cytotoxic activity with IC50 in the range of 7.98-60 μM. The flow cytometry analysis of the four human cancer cell lines treated with 6e and 5b showed that 6e induced cell cycle arrest at G2/M phase and apoptosis as well. The effect of quinolines on tubulin polymerization was also evaluated. Compound 6e that demonstrated the best antiproliferative activity in the series was identified as the most potent inhibitor of tubulin polymerization as well. Molecular docking studies of 6e into the colchicine-binding site of tubulin displayed possible mode of interaction between this compound and tubulin. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Design and implementation of an integrated architecture for massive parallel data treatment of analogue signals supplied by silicon detectors of very high spatial resolution

    International Nuclear Information System (INIS)

    Michel, J.

    1993-02-01

    This doctorate thesis studies an integrated architecture designed to a parallel massive treatment of analogue signals supplied by silicon detectors of very high spatial resolution. The first chapter is an introduction presenting the general outline and the triggering conditions of the spectrometer. Chapter two describes the operational structure of a microvertex detector made of Si micro-plates associated to the measuring chains. Information preconditioning is related to the pre-amplification stage, to the pile-up effects and to the reduction in the time characteristic due to the high counting rates. The chapter three describes the architecture of the analogue delay buffer, makes an analysis of the intrinsic noise and presents the operational testings and input/output control operations. The fourth chapter is devoted to the description of the analogue pulse shape processor and gives also the testings and the corresponding measurements on the circuit. Finally, the chapter five deals with the simplest modeling of the entire conditioning chain. Also, the testings and measuring procedures are here discussed. In conclusion the author presents some prospects for improving the signal-to-noise ratio by summation of the de-convoluted micro-paths. 78 refs., 78 figs., 1 annexe

  11. Radioiodinated diacylglycerol analogue: a potential imaging agent for single-photon emission tomographic investigations of cerebral ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Ohmori, Y. [Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto (Japan); Imahori, Y. [Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto (Japan); Ueda, S. [Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto (Japan); Fujii, R. [Nishijin Hospital, Kyoto (Japan); Wakita, K. [Nishijin Hospital, Kyoto (Japan); Inoue, M. [Daiichi Radioisotope Laboratories, Chiba (Japan); Tazawa, S. [Daiichi Radioisotope Laboratories, Chiba (Japan)

    1996-03-01

    Phospholipid metabolism is closely related to membrane perturbation in cerebral ischaemia. We investigated in vivo topographical lipid metabolism using an iodine-123-labelled diacylglycerol analogue, (1-(15-(4-iodine-123-iodophenyl)-pentadecanoyl)-2-stearoyl-rac-glycerol) ({sup 123}I-labelled DAG), in a middle cerebral artery (MCA) occlusion model with the aim of positive imaging of ischaemic insult. Sprague-Dawley rats underwent coagulation of the MCA to induce permanent occlusion. MCA occlusion times prior to injection of {sup 123}I-labelled DAG ranged from 15 min to 14 days. Each rat was injected with 11-37 MBq of {sup 123}I-labelled DAG. After 30 min, in vivo autoradiographs were reconstructed. Scanning of the living rat brain in this MCA occlusion model was performed. Cerebral infarctions were recognized in the frontal cortex, the parietal cortex and the lateral portion of the caudate-putamen by 2, 3, 5-triphenyltetrazolium hydrochloride staining. In infarcted regions (region 1), {sup 123}I-labelled DAG incorporation showed a decrease up to 12 h; it then increased up to 6 days and decreased thereafter. In peri-infarcted regions (region 2), the incorporation showed almost no change up to 12 h, then increased up to 5-6 days and decreased thereafter. In other regions (region 3), the incorporation showed no change. Lipid analysis showed that {sup 123}I-labelled DAG was metabolized to 15-(4-iodine-123-iodophenyl)-pentadecanoic acid by DAG lipase and to {sup 123}I-labelled phosphatidylcholine. Scanning of the ischaemic region showed higher accumulation than on the non-lesioned side. We established a method to visualize ischaemic foci as positive images. The early changes in {sup 123}I-labelled DAG incorporation were related to DAG lipase, which degraded the accumulated intrinsic DAG, and increased {sup 123}I-labelled DAG incorporation in the chronic stage involves several aspects of neural destruction in the process of autolysis.

  12. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial.

    Science.gov (United States)

    de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B; Kuiken, Sjoerd D; Weijer, Sebastiaan; van Nieuwkerk, Carin M J; Zaaijer, Hans L; Molenkamp, Richard; Takkenberg, R Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W

    2017-08-01

    Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen [anti-HBs]). We assessed HBsAg loss during peg-interferon-alfa-2a (peg-IFN) and nucleotide analogue combination therapy in patients with chronic hepatitis B with a low viral load. In this randomised controlled, open-label trial, patients were enrolled from the Academic Medical Center (AMC), Amsterdam, Netherlands. Eligible patients were HBsAg positive and hepatitis B e antigen (HBeAg) negative for more than 6 months, could be treatment naive or treatment experienced, and had alanine aminotransferase (ALT) concentrations less than 5 × upper limit of normal (ULN). Participants were randomly assigned (1:1:1) by a computerised randomisation programme (ALEA Randomisation Service) to receive peg-IFN 180 μg/week plus adefovir 10 mg/day, peg-IFN 180 μg/week plus tenofovir disoproxil fumarate 245 mg/day, or no treatment for 48 weeks. The primary endpoint was the proportion of patients with serum HBsAg loss among those who received at least one dose of study drug or had at least one study visit (modified intention-to-treat population [mITT]). All patients have finished the initial study of 72 weeks and will be observed for up to 5 years of follow-up. This study is registered with ClinicalTrials.gov, number NCT00973219. Between Aug 4, 2009, and Oct 17, 2013, 167 patients were screened for enrolment, of whom 151 were randomly assigned (52 to peg-IFN plus adefovir, 51 to peg-IFN plus tenofovir, and 48 to no treatment). 46 participants in the peg-IFN plus adefovir group, 45 in the peg-IFN plus tenofovir group, and 43 in the no treatment group began treatment or observation and were included in the mITT population. At week 72, two (4%) patients in the peg-IFN plus adefovir group and two (4

  13. Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly.

    Science.gov (United States)

    Auriemma, Renata S; Grasso, Ludovica F S; Galdiero, Mariano; Galderisi, Maurizio; Pivonello, Claudia; Simeoli, Chiara; De Martino, Maria Cristina; Ferrigno, Rosario; Negri, Mariarosaria; de Angelis, Cristina; Pivonello, Rosario; Colao, Annamaria

    2017-03-01

    To date, no data are available on the effects of long-term combined treatment with somatostatin analogues (SA) and pegvisomant (PEG) on cardiovascular complications in acromegaly. The current study aimed at investigating the effects of long-term SA + PEG on cardiac structure and performance. Thirty-six patients (14 M, 22 F, aged 52.3 ± 10.2 years) entered this study. Weight, BMI, systolic (SBP) and diastolic (DBP) blood pressure, IGF-I, fasting glucose (FG), fasting insulin (FI), HOMA-IR, HbA 1c , and lipids were evaluated at baseline (T0), after long-term (median 36 months) SA (T1), after 12 (T12) and 60 (T60) months of SA + PEG, and at last follow-up (LFU, median 78 months). At each time point, all patients underwent echocardiography. At T1, induced a slight but not significant decrease in IGF-I (p = 0.077), whereas FI (p = 0.004), HOMA-IR (p = 0.013), ejection fraction (EF, p = 0.013), early (E) to late (A) ventricular filling velocities (E/A, p = 0.001), and isovolumetric relaxation time (IVRT, p = 0.000) significantly improved. At T12, IGF-I (p = 0.000) significantly reduced compared to T0, and FI (p = 0.001), HOMA-IR (p = 0.000), LVMI (p = 0.000), and E/A (p = 0.006) further improved compared to T1. At T60, FI (p = 0.027), HOMA-IR (p = 0.049), and E/A (p = 0.005) significantly improved as compared to T1. At LFU IGF-I normalized in 83.3 %, FI (p = 0.000), HOMA-IR (p = 0.000), LVMi (p = 0.000), and E/A (p = 0.005) further improved as compared to T1. PEG dose significantly correlated with LVMi at T12 (r = 0.575, p = 0.000) and T60 (r = 0.403, p = 0.037). Long-term PEG addition to SA improves cardiac structure and performance, particularly diastolic dysfunction, in acromegalic patients resistant to SA.

  14. Curcumin and treatment of melanoma: The potential role of microRNAs.

    Science.gov (United States)

    Lelli, Diana; Pedone, Claudio; Sahebkar, Amirhosssein

    2017-04-01

    Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease Stages 2-5 and on dialysis.

    Science.gov (United States)

    Shroff, Rukshana; Wan, Mandy; Nagler, Evi V; Bakkaloglu, Sevcan; Cozzolino, Mario; Bacchetta, Justine; Edefonti, Alberto; Stefanidis, Constantinos J; Vande Walle, Johan; Ariceta, Gema; Klaus, Günter; Haffner, Dieter; Schmitt, Claus Peter

    2017-07-01

    In patients with chronic kidney disease (CKD), renal synthesis of active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D)] declines and is associated with hypocalcaemia, secondary hyperparathyroidism and the spectrum of CKD-mineral and bone disorder (MBD). In advanced CKD, active vitamin D analogues, including alfacalcidol, calcitriol and paricalcitol, are routinely administered. There are few studies on the use of vitamin D analogues in children with CKD and on dialysis. It is difficult to define bone-specific outcomes that can guide treatment with active vitamin D analogues in children with CKD-MBD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis WGs has developed recommendations for the use of active vitamin D therapy in children with CKD and on dialysis. A second document in parallel with this one covers treatment recommendations for native vitamin D therapy. The WGs have performed an extensive literature review to include systematic reviews and randomized controlled trials in adults and children with CKD and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to develop and grade the recommendations. In the absence of applicable study data, the opinion of experts from the ESPN CKD-MBD and Dialysis WGs is provided, but clearly GRADE-ed as such and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  16. Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Callesen, Nicoline F; Mathiesen, Jonathan Michael; Ringholm, Lene

    2013-01-01

    Objective: To compare glycaemic control and pregnancy outcome in women with type 1 diabetes treated with the long-acting insulin analogues detemir or glargine. Methods: Retrospective study of singleton pregnancies from 2007 to 2011 in women with type 1 diabetes with a single living fetus at 22.......046). No perinatal deaths were observed. One offspring in each group was born with a major congenital malformation. Conclusions: Glycaemic control and pregnancy outcome were comparable in women using insulin detemir or glargine, except for a lower prevalence of large for gestational age infants in women on glargine...

  17. Evaluation of technetium-99m/rhenium labelled nucleoside analogues as potential radiotracers in oncology[Dissertation 17173

    Energy Technology Data Exchange (ETDEWEB)

    Desbouis, D

    2007-07-01

    Over the last decade, suicide gene therapy has emerged as a very promising method to treat cancer. This therapy consists of introducing new genetic material into the nucleus of cancer cells so that they express a therapeutic protein. The protein leads to a therapeutic effect upon interaction with a prodrug. The most widely used system is the combination of the enzyme Herpes Simplex Virus Thymidine Kinase of type 1 (HSV1-TK) with the nontoxic antiviral prodrug gancyclovir. The efficiency of protein expression is crucial for a successful therapy. Several Positron Emission Tomography (PET) tracers such as 9-[4-[{sup 18}F]fluoro-3-(hydroxymethyl)butyl]guanine [{sup 18}F]FHBG) or [{sup 124}I]iodo-2'-fluoro-2'-deoxy-l-{beta}-D-arabino-furanosyluracil ({sup 124}I]FIAU) have been shown to be suitable probes for reporting HSV1-TK expression. One aspect of this work was to develop Single Photon Emission Tomography (SPET) reporter probes based on the inexpensive technetium-99m whose physical properties are well-suited for diagnosis (t{sub 1/2} = 6.02 h; E{sub {gamma}} = 140 keV). A series of complexes was prepared by derivatizing the precursor 5'-amino-5'-deoxythymidine at position N5' in order to introduce spacers of various lengths ({approx} 0-30 aangstroem) carrying tridentate metal chelating entities such as iminodiacetic acid and picolylamine-N-monoacetic acid. The nucleoside derivatives were reacted with the precursors [ReBr{sub 3}(CO){sub 3}]{sup 2-} and [{sup 99m}Tc(OH{sub 2}){sub 3}(CO){sub 3}]{sup +} to form water-stable organometallic thymidine complexes. Unexpectedly, most of the compounds showed no inhibition of HSV1-TK but a mixed inhibition of the human cytosolic thymidine kinase with K{sub iu} values ranging from 4.4-334 {mu}M. Competitive inhibition of HSV1-TK was only observed for the thymidine analogue in which the base and the metal core were separated by a spacer of approximately 30 aangstroem length (K{sub i} = 16.3 {+-} 4.6 {mu

  18. Petroleum potential of Oligocene lacustrine mudstones and coals at Dong Ho, Vietnam — an outcrop analogue to terrestrial source rocks in the greater Song Hong Basin

    Science.gov (United States)

    Petersen, H. I.; Andersen, C.; Anh, P. H.; Bojesen-Koefoed, J. A.; Nielsen, L. H.; Nytoft, H. P.; Rosenberg, P.; Thanh, L.

    2001-02-01

    The outcrop of Oligocene age at Dong Ho, northern Vietnam, may constitute an immature analogue to offshore terrestrial source rocks in the greater Song Hong Basin. The outcrop includes an interval with two source rocks: (1) highly oil-prone carbonaceous mudstones containing kerogen types IIA and IIA/I, and with TOC contents from 6.48 to 16.89 wt%, and HI values from 472 to 690; and (2) oil-prone humic coals (kerogen type III) with HI values from 200 to 242. The mudstones were deposited in oxygen-deficient lakes, which on occasion were subject to marine influence, and the coals accumulated in freshwater peat-forming mires. The coals have broad activation energy ( Ea) distributions, while the mudstones have Ea distributions characterised by a pronounced principal Ea. During artificial maturation about 16-17% of the organic carbon in the coals and 45-50% of the organic carbon in the mudstones participated in petroleum formation. The two source rocks primary generate oil and secondary generate gas, however, the mudstones realised the majority of their potential over a more narrow temperature range than the coals. The excellent generative potential of the terrestrial source rocks at Dong Ho is encouraging for offshore exploration for reservoirs charged by Cenozoic rift-lake successions.

  19. Virtual screening and statistical analysis in the design of new caffeine analogues molecules with potential epithelial anticancer activity.

    Science.gov (United States)

    Costa, Josivan da Silva; Costa, Karina Da Silva Lopes; Cruz, Josiane Viana; Ramosb, Ryan da Silva; Silva, Luciane Barros; Barros Brasilc, Davi Do Socorro; Henrique Tomich de Paula da Silva, Carlos; Santos, Cleydson Breno Rodrigues Dos; Macêdoe, Williams Jorge da Cruz

    2017-07-11

    About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the world health organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Analogue computing methods

    CERN Document Server

    Welbourne, D

    1965-01-01

    Analogue Computing Methods presents the field of analogue computation and simulation in a compact and convenient form, providing an outline of models and analogues that have been produced to solve physical problems for the engineer and how to use and program the electronic analogue computer. This book consists of six chapters. The first chapter provides an introduction to analogue computation and discusses certain mathematical techniques. The electronic equipment of an analogue computer is covered in Chapter 2, while its use to solve simple problems, including the method of scaling is elaborat

  1. Novel limonene phosphonate and farnesyl diphosphate analogues: design, synthesis, and evaluation as potential protein-farnesyl transferase inhibitors.

    Science.gov (United States)

    Eummer, J T; Gibbs, B S; Zahn, T J; Sebolt-Leopold, J S; Gibbs, R A

    1999-02-01

    Limonene and its metabolite perillyl alcohol are naturally-occurring isoprenoids that block the growth of cancer cells both in vitro and in vivo. This cytostatic effect appears to be due, at least in part, to the fact that these compounds are weak yet selective and non-toxic inhibitors of protein prenylation. Protein-farnesyl transferase (FTase), the enzyme responsible for protein farnesylation, has become a key target for the rational design of cancer chemotherapeutic agents. Therefore, several alpha-hydroxyphosphonate derivatives of limonene were designed and synthesized as potentially more potent FTase inhibitors. A noteworthy feature of the synthesis was the use of trimethylsilyl triflate as a mild, neutral deprotection method for the preparation of sensitive phosphonates from the corresponding tert-butyl phosphonate esters. Evaluation of these compounds demonstrates that they are exceptionally poor FTase inhibitors in vitro (IC50 > or = 3 mM) and they have no effect on protein farnesylation in cells. In contrast, farnesyl phosphonyl(methyl)phosphinate, a diphosphate-modified derivative of the natural substrate farnesyl diphosphate, is a very potent FTase inhibitor in vitro (Ki=23 nM).

  2. Insulin analogues and cancer: a note of caution

    Directory of Open Access Journals (Sweden)

    Joseph A.M.J.L. eJanssen

    2014-05-01

    Full Text Available Abstract In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogues are safe. In line with these findings, we observed that serum of diabetic patients treated with insulin analogues, compared to that of diabetic patients treated with human insulin, did not induce an increased phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor (IGF-IR. However, the classical model of the IGF-IR signaling may be insufficient to explain (all mitogenic effects of insulin analogues since also non-canonical signaling pathways of the IGF-IR may play a major role in this respect. Although phosphorylation of tyrosine residues of the IGF-IR is generally considered to be the initial activation step within the intracellular IGF-IR signaling pathway, it has been found that cells undergo a signaling switch under hyperglycemic conditions. After this switch, a completely different mechanism is utilized to activate the mitogenic (mitogen-activated protein kinase (MAPK pathways of the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At present it is unknown whether activation of this alternative intracellular pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is stronger in patients treated with (some insulin analogues than in patients treated with human insulin. In addition, it is unknown whether the insulin receptors (IRs also undergo a signaling switch during hyperglycemia. This should be investigated in future studies. Finally, relative overexpression of IR isoform A (IR-A in (pre cancer tissues may play a key role in the development and progression of human cancers during treatment with insulin (analogues. Further

  3. PTH analogues and osteoporotic fractures

    NARCIS (Netherlands)

    Verhaar, H.J.; Lems, W.F.

    2010-01-01

    Importance of the field: At present there are two parathyroid hormone (PTH) analogues (PTH 1 34 and PTH 1 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 34 and PTH 1 84) and in men (PTH 1 34 only) who are at increased risk of having a fracture. Areas

  4. Analogue MIMO Detection

    Directory of Open Access Journals (Sweden)

    McNamara Darren

    2006-01-01

    Full Text Available In this contribution we propose an analogue receiver that can perform turbo detection in MIMO systems. We present the case for a receiver that is built from nonlinear analogue devices, which perform detection in a "free-flow" network (no notion of iterations. This contribution can be viewed as an extension of analogue turbo decoder concepts to include MIMO detection. These first analogue implementations report reductions of few orders of magnitude in the number of required transistors and in consumed energy, and the same order of improvement in processing speed. It is anticipated that such analogue MIMO decoder could bring about the same advantages, when compared to traditional digital implementations.

  5. Survival of spermatogonial stem cells in the rat after split dose irradiation during LH-RH analogue treatment

    International Nuclear Information System (INIS)

    Kroonenburgh, M.J.P.G. van; Daal, W.A.J. van; Beck, J.L.; Vemer, H.M.; Rolland, R.

    1987-01-01

    A rat model has been created in which a single injection of an LH-RH analogue depot preparation (Zoladex, ICI 118630) produced a temporary interruption of the pituitary-gonadal axis. This effect applied during irradiation was investigated as a possible mechanism to protect the testis from radiation damage. A local testicular irradiation dose of 6.0 Gy was given either as a single dose or as a fractionated (2 x 3.0 Gy) dose at different time intervals ranging from 8 to 72 h. Stem cell survival was measured 11 weeks after irradiation by means of the repopulation index and the number of haploid cells (spermatids) measured by flow cytometry. Serum gonadotrophins and testosterone concentrations were measured to evaluate hormonal recovery. No significant differences were observed between serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone and the duration of the fractionation interval. Stem cell survival was higher following fractionated irradiation in comparison with the single dose. For the 8 h interval an increase in recovery ratio was found, amounting to a factor of 5 of the single dose value. The fluctuating pattern of the recovery curves indicated changes in radiosensitivity of stem cells. The combination of hormonal inhibition of spermatogenesis and fractionated irradiation led to a decrease in the absolute numbers of stem cells. However, the stem cell recovery curves were identical to those seen without hormonal inhibition. It was concluded that hormonal pretreatment with Zoladex during split dose irradiation had no protective effect on stem cell survival. 37 refs.; 4 figs

  6. The Effect of an Educating versus Normalizing Approach on Treatment Motivation in Patients Presenting with Delusions: An Experimental Investigation with Analogue Patients

    Directory of Open Access Journals (Sweden)

    Eva Lüllmann

    2013-01-01

    Full Text Available Until recently a widespread recommendation for clinicians was not to respond to the content of patients' delusions but to stress at an early time point that the patient has a mental illness (educating approach. An opposed recommendation is to validate the patients’ symptoms and normalize them (normalizing approach. This study used an experimental design to compare the impact of these two approaches on treatment motivation (TM. A cover story about a person who develops persecutory delusions was used to guide a sample of 81 healthy participants who served as analogue patients into imagining experiencing delusions. This was followed by a random assignment to either an educating or a normalizing consultation with a fictive clinician. Consultations only differed in content. Finally, we assessed the participants' motivation to accept medication (Medication TM, psychological treatment (Psychological TM, and treatment offered by this particular clinician independent of the kind of treatment (Clinician-related TM. Participants in the normalizing condition showed higher Clinician-related and Psychological TM than those in the educating condition. Medication TM was unaffected by condition. Following our results using a normalizing approach seems to be advisable in a first-contact situation with patients with delusions and favourable to a simple educating approach.

  7. Denitrifying bioreactor clogging potential during wastewater treatment

    Science.gov (United States)

    Chemoheterotrophic denitrification technologies using woodchips as a solid carbon source (i.e., woodchip bioreactors) have been widely trialed for treatment of diffuse-source agricultural nitrogen pollution. There is growing interest in the use of this simple, relatively low-cost biological wastewat...

  8. Geothermal areas as analogues to chemical processes in the near-field and altered zone of the potential Yucca Mountain, Nevada repository

    Energy Technology Data Exchange (ETDEWEB)

    Bruton, C.J.; Glassley, W.E.; Meike, A.

    1995-02-01

    The need to bound system performance of the potential Yucca Mountain repository for thousands of years after emplacement of high-level nuclear waste requires the use of computer codes. The use of such codes to produce reliable bounds over such long time periods must be tested using long-lived natural and historical systems as analogues. The geothermal systems of the Taupo Volcanic Zone (TVZ) in New Zealand were selected as the site most amenable to study. The rocks of the TVZ are silicic volcanics that are similar in composition to Yucca Mountain. The area has been subjected to temperatures of 25 to 300 C which have produced a variety of secondary minerals similar to those anticipated at Yucca Mountain. The availability of rocks, fluids and fabricated materials for sampling is excellent because of widespread exploitation of the systems for geothermal power. Current work has focused on testing the ability of the EQ3/6 code and thermodynamic data base to describe mineral-fluid relations at elevated temperatures. Welfare starting long-term dissolution/corrosion tests of rocks, minerals and manufactured materials in natural thermal features in order to compare laboratory rates with field-derived rates. Available field data on rates of silica precipitation from heated fluids have been analyzed and compared to laboratory rates. New sets of precipitation experiments are being planned. The microbially influenced degradation of concrete in the Broadlands-Ohaaki geothermal field is being characterized. The authors will continue to work on these projects in FY 1996 and expand to include the study of naturally occurring uranium and thorium series radionuclides, as a prelude to studying radionuclide migration in heated silicic volcanic rocks. 32 refs.

  9. Geothermal areas as analogues to chemical processes in the near-field and altered zone of the potential Yucca Mountain, Nevada repository

    International Nuclear Information System (INIS)

    Bruton, C.J.; Glassley, W.E.; Meike, A.

    1995-02-01

    The need to bound system performance of the potential Yucca Mountain repository for thousands of years after emplacement of high-level nuclear waste requires the use of computer codes. The use of such codes to produce reliable bounds over such long time periods must be tested using long-lived natural and historical systems as analogues. The geothermal systems of the Taupo Volcanic Zone (TVZ) in New Zealand were selected as the site most amenable to study. The rocks of the TVZ are silicic volcanics that are similar in composition to Yucca Mountain. The area has been subjected to temperatures of 25 to 300 C which have produced a variety of secondary minerals similar to those anticipated at Yucca Mountain. The availability of rocks, fluids and fabricated materials for sampling is excellent because of widespread exploitation of the systems for geothermal power. Current work has focused on testing the ability of the EQ3/6 code and thermodynamic data base to describe mineral-fluid relations at elevated temperatures. Welfare starting long-term dissolution/corrosion tests of rocks, minerals and manufactured materials in natural thermal features in order to compare laboratory rates with field-derived rates. Available field data on rates of silica precipitation from heated fluids have been analyzed and compared to laboratory rates. New sets of precipitation experiments are being planned. The microbially influenced degradation of concrete in the Broadlands-Ohaaki geothermal field is being characterized. The authors will continue to work on these projects in FY 1996 and expand to include the study of naturally occurring uranium and thorium series radionuclides, as a prelude to studying radionuclide migration in heated silicic volcanic rocks. 32 refs

  10. Análogos de la somatostatina en el tratamiento de la retinopatía diabética Somatostatin analogues in the treatment of diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Juana Elvira Maciques Rodríguez

    2012-04-01

    Full Text Available La retinopatía diabética constituye un importante problema de salud por la discapacidad visual que provoca. El tratamiento de elección continúa siendo la fotocoagulación láser, pero en ocasiones hay formas avanzadas en que la respuesta es pobre y la evolución tórpida. Se continúan buscando otras alternativas de tratamiento que puedan mejorar la evolución, como son los esteroides y antiangiogénicos. Con el objetivo de reagrupar información actual sobre este grupo de medicamentos (análogos de la somatostatina, los cuales tienen efectos antiangiogénicos y han sido usados en el tratamiento de la retinopatía diabética proliferativa y el edema macular diabético, se realizó esta revisión. Los análogos de la somatostatina han mostrado ser eficaces, fundamentalmente, en el control de los fenómenos hemorrágicos y proliferativos en la retinopatía diabética proliferativa, y al mejorar también la integridad de la barrera hematoretiniana, ofrecen una alternativa de tratamiento para el edema macular diabético, fundamentalmente, cuando la respuesta al láser no resulta favorable.The diabetic retinopathy is an important health problem due to visual disability provoked. The choice treatment still remains the laser photocoagulation, but sometimes there is advanced ways in which the response is poor and the course is torpid. Other alternatives of treatment are look for to improve the course including the steroids and anti-angiogenic. The aim of present review was to regroup the current information on this group of drugs (somatostatin analogues, which has a anti-angiogenic effect and used in the treatment of proliferative diabetic retinopathy and the diabetic macular edema. The somatostatin analogues have shown to be effective, mainly in the control of hemorrhagic and proliferative phenomena and to also improve the integrity of the hematoretinal barrier, offer an alternative of treatment for diabetic macular edema, mainly when the response

  11. Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

    NARCIS (Netherlands)

    van der Kaay, Danielle C. M.; de Jong, Frank H.; Rose, Susan R.; Odink, Roelof J. H.; Bakker-van Waarde, Willie M.; Sulkers, Eric J.; Hokken-Koelega, Anita C. S.

    2009-01-01

    Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone

  12. Overnight levels of luteinizing hormone, follicle-stimulating hormone and growth hormone before and during gonadotropin-releasing hormone analogue treatment in short boys born small for gestational age

    NARCIS (Netherlands)

    D.C.M. van der Kaay (Danielle); F.H. de Jong (Frank); S.R. Rose (Susan); R.J.H. Odink (Roelof); W.M. Bakker-Van Waarde (Willie); E.J. Sulkers (Eric); A.C.S. Hokken-Koelega (Anita)

    2009-01-01

    textabstractAims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare

  13. Valuing Treatments for Parkinson Disease Incorporating Process Utility: Performance of Best-Worst Scaling, Time Trade-Off, and Visual Analogue Scales.

    Science.gov (United States)

    Weernink, Marieke G M; Groothuis-Oudshoorn, Catharina G M; IJzerman, Maarten J; van Til, Janine A

    2016-01-01

    The objective of this study was to compare treatment profiles including both health outcomes and process characteristics in Parkinson disease using best-worst scaling (BWS), time trade-off (TTO), and visual analogue scales (VAS). From the model comprising of seven attributes with three levels, six unique profiles were selected representing process-related factors and health outcomes in Parkinson disease. A Web-based survey (N = 613) was conducted in a general population to estimate process-related utilities using profile-based BWS (case 2), multiprofile-based BWS (case 3), TTO, and VAS. The rank order of the six profiles was compared, convergent validity among methods was assessed, and individual analysis focused on the differentiation between pairs of profiles with methods used. The aggregated health-state utilities for the six treatment profiles were highly comparable for all methods and no rank reversals were identified. On the individual level, the convergent validity between all methods was strong; however, respondents differentiated less in the utility of closely related treatment profiles with a VAS or TTO than with BWS. For TTO and VAS, this resulted in nonsignificant differences in mean utilities for closely related treatment profiles. This study suggests that all methods are equally able to measure process-related utility when the aim is to estimate the overall value of treatments. On an individual level, such as in shared decision making, BWS allows for better prioritization of treatment alternatives, especially if they are closely related. The decision-making problem and the need for explicit trade-off between attributes should determine the choice for a method. Copyright © 2016. Published by Elsevier Inc.

  14. Investigation of hypereosinophilia and potential treatments.

    Science.gov (United States)

    Lilliehöök, Inger; Tvedten, Harold

    2003-11-01

    Hypereosinophilia is excessive eosinophilia and has been defined in dogs and cats as eosinophils greater than 5 x 10(9)/L (> 5000/microL). Canine breeds with a predisposition to higher eosinophil counts or certain eosinophilic diseases include the Rottweiler, German Shepard, Siberian Husky, Alaskan Malamute, and Cavalier King Charles Spaniel. Two of the more common causes of canine hypereosinophilia are pulmonary infiltrates with eosinophils (PIE) and gastrointestinal disease. The highest eosinophil counts are expected in dogs with pneumonia or PIE. The most common cause of eosinophilia in cats is flea allergy. The greatest eosinophilia occurs in cats with flea allergy, feline asthma, and eosinophilic granuloma. Innovative recent treatments for human patients with asthma have been successful in reducing eosinophil numbers but have had a confusing and disappointing lack of reducing symptoms. The role of eosinophils in many eosinophilic diseases remains a mystery.

  15. Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664 or nitroglycerin

    Directory of Open Access Journals (Sweden)

    Sidi Avner

    2008-01-01

    Full Text Available In patients at risk for sudden ethanol (ETOH intravascular absorption, prompt treatment of pulmonary hypertension (PHTN will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664 and nitroglycerin (NTG during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT, as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP, and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg ( n = 7 normal saline, a 500-μg/kg bolus of UK343-664 ( n = 8, or NTG 1 μg/kg ( n = 8; each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP, and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR. Within 2 minutes after treatment with either drug, CVP, heart rate (HR, and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241±579 and 1224±494 dyne · cm/sec 5 , which were threefold-to-fourfold increased baseline values, to 672±308 and 538±203 dyne · cm/sec 5 respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from

  16. Targeting sclerostin as potential treatment of osteoporosis.

    Science.gov (United States)

    Papapoulos, Socrates E

    2011-03-01

    In recent years, study of rare bone diseases has led to the identification of signalling pathways that regulate bone formation and provided targets for the development of novel therapeutic agents to stimulate bone formation in patients with osteoporosis. Studies of two bone sclerosing dysplasias, sclerosteosis and van Buchem disease led to the identification of sclerostin, a negative regulator of bone formation. Sclerostin binds to LRP5/6 and inhibits Wnt signalling, but its precise molecular mechanism of action is not yet known. Its expression is restricted in the skeleton to osteocytes and is modified by mechanical loading and parathyroid hormone treatment. Sclerostin deficiency reproduces the findings of the human diseases in mice, while sclerostin excess leads to bone loss and reduced bone strength. An antibody to sclerostin increased bone formation dramatically at all bone envelopes in ovariectomised rats and intact monkeys, without affecting bone resorption and improved bone strength. In initial human studies, a single injection of the antibody to postmenopausal women increased serum P1NP and transiently decreased serum CTX. Clinical phase II studies with this antibody are currently underway.

  17. Design and Synthesis of Analogues of Marine Natural Product Galaxamide, an N-methylated Cyclic Pentapeptide, as Potential Anti-Tumor Agent in Vitro

    Directory of Open Access Journals (Sweden)

    Jignesh Lunagariya

    2016-09-01

    Full Text Available Herein, we report design and synthesis of novel 26 galaxamide analogues with N-methylated cyclo-pentapeptide, and their in vitro anti-tumor activity towards the panel of human tumor cell line, such as, A549, A549/DPP, HepG2 and SMMC-7721 using MTT assay. We have also investigated the effect of galaxamide and its representative analogues on growth, cell-cycle phases, and induction of apoptosis in SMMC-7721 cells in vitro. Reckon with the significance of conformational space and N-Me aminoacid (aa comprising this compound template, we designed the analogues with modification in N-Me-aa position, change in aa configuration from l to d aa and substitute one Leu-aa to d/l Phe-aa residue with respective to the parent structure. The efficient solid phase parallel synthesis approach is employed for the linear pentapeptide residue containing N-Me aa, followed by solution phase macrocyclisation to afford target cyclo pentapeptide compounds. In the present study, all galaxamide analogues exhibited growth inhibition in A549, A549/DPP, SMMC-7721 and HepG2 cell lines. Compounds 6, 18, and 22 exhibited interesting activities towards all cell line tested, while Compounds 1, 4, 15, and 22 showed strong activity towards SMMC-7221 cell line in the range of 1–2 μg/mL IC50. Flow cytometry experiment revealed that galaxamide analogues namely Compounds 6, 18, and 22 induced concentration dependent SMMC-7721 cell apoptosis after 48 h. These compounds induced G0/G1 phase cell-cycle arrest and morphological changes indicating induction of apoptosis. Thus, findings of our study suggest that the galaxamide and its analogues 6, 18 and 22 exerted growth inhibitory effect on SMMC-7721 cells by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Compound 1 showed promising anti-tumor activity towards SMMC-7721 cancer cell line, which is 9 and 10 fold higher than galaxamide and reference DPP (cisplatin, respectively.

  18. Treatment of experimental allergic encephalomyelitis (EAE) by a rationally designed cyclic analogue of myelin basic protein (MBP) epitope 72-85.

    Science.gov (United States)

    Tselios, T; Daliani, I; Deraos, S; Thymianou, S; Matsoukas, E; Troganis, A; Gerothanassis, I; Mouzaki, A; Mavromoustakos, T; Probert, L; Matsoukas, J

    2000-12-18

    In this report the rational design, synthesis and pharmacological properties of an amide-linked cyclic antagonist analogue of the guinea pig myelin basic protein epitope MBP(72-85) are described. Design of the potent cyclic analogue was based on 2D NOESY nuclear magnetic resonance and molecular dynamics studies carried out in the linear antagonist Ala81MBP(72-85). The cyclic antagonist completely prevented the induction of experimental allergic/autoimmune encephalomyelitis when coinjected with linear and cyclic agonist analogues MBP(72-85) and cyclo(2-9)MBP(72-85).

  19. Structure-activity relationships of β-hydroxyphosphonate nucleoside analogues as cytosolic 5'-nucleotidase II potential inhibitors: synthesis, in vitro evaluation and molecular modeling studies.

    Science.gov (United States)

    Meurillon, Maïa; Marton, Zsuzsanna; Hospital, Audrey; Jordheim, Lars Petter; Béjaud, Jérôme; Lionne, Corinne; Dumontet, Charles; Périgaud, Christian; Chaloin, Laurent; Peyrottes, Suzanne

    2014-04-22

    The cytosolic 5'-nucleotidase II (cN-II) has been proposed as an attractive molecular target for the development of novel drugs circumventing resistance to cytotoxic nucleoside analogues currently used for treating leukemia and other malignant hemopathies. In the present work, synthesis of β-hydroxyphosphonate nucleoside analogues incorporating modifications either on the sugar residue or the nucleobase, and their in vitro evaluation towards the purified enzyme were carried out in order to determine their potency towards the inhibition of cN-II. In addition to the biochemical investigations, molecular modeling studies revealed important structural features for binding affinities towards the target enzyme. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. 3D-QSAR study and design of 4-hydroxyamino α-pyranone carboxamide analogues as potential anti-HCV agents

    Science.gov (United States)

    Li, Wenlian; Xiao, Faqi; Zhou, Mingming; Jiang, Xuejin; Liu, Jun; Si, Hongzong; Xie, Meng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

    2016-09-01

    The three dimensional-quantitative structure activity relationship (3D-QSAR) study was performed on a series of 4-hydroxyamino α-pyranone carboxamide analogues using comparative molecular similarity indices analysis (COMSIA). The purpose of the present study was to develop a satisfactory model providing a reliable prediction based on 4-hydroxyamino α-pyranone carboxamide analogues as anti-HCV (hepatitis C virus) inhibitors. The statistical results and the results of validation of this optimum COMSIA model were satisfactory. Furthermore, analysis of the contour maps helped to provide guidelines for finding structural requirement. Therefore, the satisfactory results from this study may provide useful guidelines for drug development of anti-HCV inhibitors.

  1. Synthesis via “click chemistry" of new triazole analogues derivatives of grandisin and veraguensin neolignans with potential trypanocidal and leishmanicidal activity

    Directory of Open Access Journals (Sweden)

    Tatiana C Bortolo

    2012-06-01

    Full Text Available Using the concept of bioisosterism, new triazole analogs were designed from the molecular modification of grandisin and veraguensin neolignans   which have a furan group that is a bioisóstere of 1,2,3-triazoles ring. In order to obtain more potent compounds, with fewer side effects, and better physical and chemical characteristics in combating leishmaniasis and chagas disease, this research group synthesized, via "Click Chemistry", eight new triazole analogues of neolignans. Thus reactions 1,3-dipolar cycloaddition of Huisgen were performed between terminal acetylenes and azides previously synthesized. The catalytic system CuSO4.5H2O/Ascorbate Sodium / CH2Cl2/H2O was used and, under this reaction conditions eight triazole analogues were synthesized in good yields. Trypanocidal activity test showed positive for the eight molecules.

  2. Effects of hypoxia-ischemia and MK-801 treatment on the binding of a phencyclidine analogue in the developing rat brain

    International Nuclear Information System (INIS)

    Silverstein, F.S.; McDonald, J.W. III; Bommarito, M.; Johnston, M.V.

    1990-01-01

    The phencyclidine analogue [ 3 H](1-[2-thienyl]cyclohexyl)piperidine ( 3 H-TCP) binds to the ion channel associated with the N-methyl-D-aspartate receptor channel complex. In vitro autoradiography indicates that the distribution of 3 H-TCP binding in brain closely parallels that of [ 3 H]glutamate binding to the N-methyl-D-aspartate receptor. In nine 7-day-old rats, an acute focal hypoxic-ischemic insult produced by unilateral carotid artery ligation and subsequent exposure to 8% oxygen acutely reduced 3 H-TCP binding ipsilateral to the ligation by 30% in the CA1, by 27% in the CA3, by 26% in the dentate gyrus, and by 17% in the striatum compared with values from the contralateral hemisphere. In 10 littermates that received 1 mg/kg of the neuroprotective noncompetitive N-methyl-D-aspartate antagonist MK-801 immediately before hypoxic exposure, the regional distribution of 3 H-TCP binding in hypoxic-ischemic brain was relatively preserved and there were no interhemispheric asymmetries in 3 H-TCP binding densities. In addition, in three unoperated rats decapitated 24 hours after MK-801 treatment, 3 H-TCP binding was reduced by 15-35%; similar bilateral suppression of 3 H-TCP binding was detected in MK-801-treated ligates. Our data indicate that 3 H-TCP autoradiography can be used to assay the efficacy of neuroprotective agents in this experimental model of perinatal stroke

  3. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence

    Energy Technology Data Exchange (ETDEWEB)

    Campana, Davide; Nori, Francesca; Cacciari, Giulia; Tomassetti, Paola [University of Bologna, Department of Medical and Surgical Sciences, Bologna (Italy); Capurso, Gabriele; Panzuto, Francesco; Delle Fave, Gianfranco [University of Rome, Digestive and Liver Disease Unit, Rome (Italy); Partelli, Stefano [Sacro Cuore Don Calabria Hospital, Department of Surgery, Negrar (Italy); University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy); Tamburrino, Domenico; Falconi, Massimo [University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy)

    2013-08-15

    Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with {sup 90}Y or {sup 177}Lu. The objective response rate was 27.5 % (partial response, PR), while 50.7 % had stable disease and 23.2 % had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided. (orig.)

  4. Advances in Drug Design Based on the Amino Acid Approach: Taurine Analogues for the Treatment of CNS Diseases

    Directory of Open Access Journals (Sweden)

    Paulo Renato Yamasaki

    2012-10-01

    Full Text Available Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer’s, Parkinson’s, epilepsy and in the damage of retinal neurons. This review describes the  CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.

  5. Hormonal changes during GnRH analogue therapy in children with central precocious puberty

    DEFF Research Database (Denmark)

    Müller, J; Juul, A; Andersson, A M

    2000-01-01

    Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both the hypoth...

  6. Application potential of carbon nanotubes in water treatment: A review.

    Science.gov (United States)

    Liu, Xitong; Wang, Mengshu; Zhang, Shujuan; Pan, Bingcai

    2013-07-01

    Water treatment is the key to coping with the conflict between people's increasing demand for water and the world-wide water shortage. Owing to their unique and tunable structural, physical, and chemical properties, carbon nanotubes (CNTs) have exhibited great potentials in water treatment. This review makes an attempt to provide an overview of potential solutions to various environmental challenges by using CNTs as adsorbents, catalysts or catalyst support, membranes, and electrodes. The merits of incorporating CNT to conventional water-treatment material are emphasized, and the remaining challenges are discussed.

  7. Andrographolide and analogues in cancer prevention.

    Science.gov (United States)

    Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

    2015-01-01

    Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

  8. Follistatin: A Potential Anabolic Treatment for Re-Innervated Muscle

    Science.gov (United States)

    2017-09-01

    slides, analyze the slides, and prepare to present data ▪ Compound Nerve Action Potentials – Review the recorded signal, extract data from the...Compound Nerve Action Potentials – Review the recorded signal, extract data from the signal, prepare to present data ▪ Follistatin ELISA – Run the...AWARD NUMBER: W81XWH-15-1-0229 TITLE: Follistatin: A Potential Anabolic Treatment for Re-Innervated Muscle PRINCIPAL

  9. Bacteriophages-potential for application in wastewater treatment processes

    International Nuclear Information System (INIS)

    Withey, S.; Cartmell, E.; Avery, L.M.; Stephenson, T.

    2005-01-01

    Bacteriophages are viruses that infect and lyse bacteria. Interest in the ability of phages to control bacterial populations has extended from medical applications into the fields of agriculture, aquaculture and the food industry. Here, the potential application of phage techniques in wastewater treatment systems to improve effluent and sludge emissions into the environment is discussed. Phage-mediated bacterial mortality has the potential to influence treatment performance by controlling the abundance of key functional groups. Phage treatments have the potential to control environmental wastewater process problems such as: foaming in activated sludge plants; sludge dewaterability and digestibility; pathogenic bacteria; and to reduce competition between nuisance bacteria and functionally important microbial populations. Successful application of phage therapy to wastewater treatment does though require a fuller understanding of wastewater microbial community dynamics and interactions. Strategies to counter host specificity and host cell resistance must also be developed, as should safety considerations regarding pathogen emergence through transduction

  10. Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients.

    Science.gov (United States)

    Faggiano, Antongiulio; Tavares, Lidice Brandao; Tauchmanova, Libuse; Milone, Francesco; Mansueto, Gelsomina; Ramundo, Valeria; De Caro, Maria Laura Del Basso; Lombardi, Gaetano; De Rosa, Gaetano; Colao, Annamaria

    2008-11-01

    In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62.5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37.5%). Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP.

  11. Remote Sensing Analysis of Recent Carbonate Platforms, East of Sabah: Potential Analogues for Miocene Carbonate Platforms of the South China Sea

    Directory of Open Access Journals (Sweden)

    Aicha Chalabi

    2014-06-01

    Full Text Available DOI: 10.17014/ijog.v7i3.141Recent carbonate platforms may provide useful analogues for fossil platforms and reefs, and could allow the generation of quantitative tools for the prediction of facies distribution, reservoir volumes, and reservoir quality. Data from these modern analogues would greatly enhance our ability to construct more reliable and calibrated reservoir models for carbonate fossil fields, such as the Miocene carbonate platforms of Central Luconia Province, Sarawak. In this study, carbonate facies maps and quantitative reservoir data will be generated by using remote sensing techniques. Satellite imageries over the carbonate platforms east of Sabah have been acquired and processed for generating facies maps. In order to produce a reliable facies map, the composition and grain size distribution of the sediments that make up individual facies must be known in order to determine the classes that have been identified on the initial facies maps. Samples collected from the Gaya and Selekan platforms were analyzed and the results of grain size analysis are illustrated.

  12. Natural analogues and radionuclide transport model validation

    International Nuclear Information System (INIS)

    Lever, D.A.

    1987-08-01

    In this paper, some possible roles for natural analogues are discussed from the point of view of those involved with the development of mathematical models for radionuclide transport and with the use of these models in repository safety assessments. The characteristic features of a safety assessment are outlined in order to address the questions of where natural analogues can be used to improve our understanding of the processes involved and where they can assist in validating the models that are used. Natural analogues have the potential to provide useful information about some critical processes, especially long-term chemical processes and migration rates. There is likely to be considerable uncertainty and ambiguity associated with the interpretation of natural analogues, and thus it is their general features which should be emphasized, and models with appropriate levels of sophistication should be used. Experience gained in modelling the Koongarra uranium deposit in northern Australia is drawn upon. (author)

  13. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    Science.gov (United States)

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

  14. The carbon-sequestration potential of municipal wastewater treatment.

    Science.gov (United States)

    Rosso, Diego; Stenstrom, Michael K

    2008-02-01

    The lack of proper wastewater treatment results in production of CO(2) and CH(4) without the opportunity for carbon sequestration and energy recovery, with deleterious effects for global warming. Without extending wastewater treatment to all urban areas worldwide, CO(2) and CH(4) emissions associated with wastewater discharges could reach the equivalent of 1.91 x 10(5) t(CO2)d(-1) in 2025, with even more dramatic impact in the short-term. The carbon sequestration benefits of wastewater treatment have enormous potential, which adds an energy conservation incentive to upgrading existing facilities to complete wastewater treatment. The potential greenhouse gases discharges which can be converted to a net equivalent CO(2) credit can be as large as 1.91 x 10(5) t(CO2)d(-1) in 2025 by 2025. Biomass sequestration and biogas conversion energy recovery are the two main strategies for carbon sequestration and emission offset, respectively. The greatest potential for improvement is outside Europe and North America, which have largely completed treatment plant construction. Europe and North America can partially offset their CO(2) emissions and receive benefits through the carbon emission trading system, as established by the Kyoto protocol, by extending existing technologies or subsidizing wastewater treatment plant construction in urban areas lacking treatment. This strategy can help mitigate global warming, in addition to providing a sustainable solution for extending the health, environmental, and humanitarian benefits of proper sanitation.

  15. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial

    NARCIS (Netherlands)

    de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B.; Kuiken, Sjoerd D.; Weijer, Sebastiaan; van Nieuwkerk, Carin M. J.; Zaaijer, Hans L.; Molenkamp, Richard; Takkenberg, R. Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W.

    2017-01-01

    Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen

  16. Assessment of dairy wastewater treatment and its potential for ...

    African Journals Online (AJOL)

    The extent of pollution of dairy wastewater treated in a septic tank and its potential for biogas production was investigated. Performance of the existing treatment system was assessed through characterization of both raw and treated effluents. From the analysis parameters likeChemical Oxygen Demand (COD), Biochemical ...

  17. Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jignesh Lunagariya

    2017-01-01

    Full Text Available Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP, and reactive oxygen species (ROS generation using flow cytometry in human breast cancer MCF-7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF-7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB-MDA-231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF-7 cells. This galaxamide analogue significantly induced apoptosis in a dose-dependent manner in MCF-7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.

  18. Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN.

    Science.gov (United States)

    Fontaine, H; Kahi, S; Chazallon, C; Bourgine, M; Varaut, A; Buffet, C; Godon, O; Meritet, J F; Saïdi, Y; Michel, M L; Scott-Algara, D; Aboulker, J P; Pol, S

    2015-01-01

    The antiviral efficacy of nucleos(t)ide analogues whose main limitation is relapse after discontinuation requires long-term therapy. To overcome the risk of relapse and virological breakthrough during long-term therapy, we performed a phase I/II, open, prospective, multicentre trial using a HBV envelope-expressing DNA vaccine. 70 patients treated effectively with nucleos(t)ide analogues for a median of 3 years (HBV DNA 120 IU/mL) or impossibility of stopping treatment at week 48. Reactivation occurred in 97% of each group after a median 28 days without liver failure but with an HBV DNA <2000 IU/mL in 33%; 99% of adverse reactions were mild to moderate. Immune responses were evaluated by enzyme-linked immunosorbent spot and proliferation assays: there was no difference in the percentage of patients with interferon-γ secreting cells and a specific T-cell proliferation to HBcAg but not to HBsAg after reactivation in each group. Although it is fairly well tolerated, the HBV DNA vaccine does not decrease the risk of relapse in HBV-treated patients or the rate of virological breakthrough, and does not restore the anti-HBV immune response despite effective viral suppression by analogues. NCT00536627. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Bacteriophages as potential treatment option for antibiotic resistant bacteria.

    Science.gov (United States)

    Bragg, Robert; van der Westhuizen, Wouter; Lee, Ji-Yun; Coetsee, Elke; Boucher, Charlotte

    2014-01-01

    The world is facing an ever-increasing problem with antibiotic resistant bacteria and we are rapidly heading for a post-antibiotic era. There is an urgent need to investigate alterative treatment options while there are still a few antibiotics left. Bacteriophages are viruses that specifically target bacteria. Before the development of antibiotics, some efforts were made to use bacteriophages as a treatment option, but most of this research stopped soon after the discovery of antibiotics. There are two different replication options which bacteriophages employ. These are the lytic and lysogenic life cycles. Both these life cycles have potential as treatment options. There are various advantages and disadvantages to the use of bacteriophages as treatment options. The main advantage is the specificity of bacteriophages and treatments can be designed to specifically target pathogenic bacteria while not negatively affecting the normal microbiota. There are various advantages to this. However, the high level of specificity also creates potential problems, the main being the requirement of highly specific diagnostic procedures. Another potential problem with phage therapy includes the development of immunity and limitations with the registration of phage therapy options. The latter is driving research toward the expression of phage genes which break the bacterial cell wall, which could then be used as a treatment option. Various aspects of phage therapy have been investigated in studies undertaken by our research group. We have investigated specificity of phages to various avian pathogenic E. coli isolates. Furthermore, the exciting NanoSAM technology has been employed to investigate bacteriophage replication and aspects of this will be discussed.

  20. Premenstrual Exacerbation of Life-Threatening Asthma: Effect of Gonadotrophin Releasing Hormone Analogue Therapy

    Directory of Open Access Journals (Sweden)

    Alun L Edwards

    1996-01-01

    Full Text Available Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

  1. Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide-Oligonucleotide Conjugates.

    Science.gov (United States)

    Taskova, Maria; Mantsiou, Anna; Astakhova, Kira

    2017-09-05

    The main objective of this work is to provide an update on synthetic nucleic acid analogues and nanoassemblies as tools in gene therapy. In particular, the synthesis and properties of peptide-oligonucleotide conjugates (POCs), which have high potential in research and as therapeutics, are described in detail. The exploration of POCs has already led to fruitful results in the treatment of neurological diseases, lung disorders, cancer, leukemia, viral, and bacterial infections. However, delivery and in vivo stability are the major barriers to the clinical application of POCs and other analogues that still have to be overcome. This review summarizes recent achievements in the delivery and in vivo administration of synthetic nucleic acid analogues, focusing on POCs, and compares their efficiency. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Allelopatic potential of weeds under the minimalization of soil treatment

    Directory of Open Access Journals (Sweden)

    Mikhail A. Mazirov

    2014-01-01

    Full Text Available The content of water-dispersible phenol substances in rhizosphere both of annual and perennial species of weeds (Cirsium arvense, Sonchus arvensis increases under soil treatment minimalization. The higher content of phenol substances of researched weeds is defined in rhizosphere of Common Couch (Agropyrum repens. The absence of intensive anthropogenic treatment of plowing layer which accumulates the significant mass of weed’s roots in the cause of much more higher allelopathic potential of some species’ of weeds. The high level of saturation by weeds in agrophytocoenosis under non-tillage soil treatment is defines the competitiveness between certain sepsis’ of weeds, especially, at the beginning of the vegetation. In this case, increasing the secretion of phenol substances is one of the physiological screenings of such competitiveness.

  3. CEC natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1986-01-01

    The second meeting of the CEC Natural Analogue Working Group took place on June 17-19, 1986, hosted by the Swiss NAGRA in Interlaken (CH). A review of recent progress in natural analogue programmes was carried out, and complemented by detailed discussions about geomicrobiology, archaeological analogues, natural colloids, and use of analogues to increase confidence in safety assessments for radioactive waste disposal. A statement drafted by the Group, and the presentations made, are put together in this report

  4. Therapeutic Potentials of Microalgae in the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Olasehinde, Tosin A; Olaniran, Ademola O; Okoh, Anthony I

    2017-03-18

    Current research is geared towards the discovery of new compounds with strong neuroprotective potential and few or no side effects compared to synthetic drugs. This review focuses on the potentials of extracts and biologically active compounds derived from microalgal biomass for the treatment and management of Alzheimer's disease (AD). Microalgal research has gained much attention recently due to its contribution to the production of renewable fuels and the ability of alga cells to produce several secondary metabolites such as carotenoids, polyphenols, sterols, polyunsaturated fatty acids and polysaccharides. These compounds exhibit several pharmacological activities and possess neuroprotective potential. The pathogenesis of Alzheimer's disease (AD) involves complex mechanisms that are associated with oxidative stress, cholinergic dysfunction, neuronal damage, protein misfolding and aggregation. The antioxidant, anticholinesterase activities as well as the inhibitory effects of some bioactive compounds from microalgae extracts on β-amyloid aggregation and neuronal death are discussed extensively. Phytochemical compounds from microalgae are used as pharmaceuticals, nutraceuticals and food supplements, and may possess neuroprotective potentials that are relevant to the management and/or treatment of AD.

  5. CEC Natural Analogue Working Group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1989-01-01

    The central theme for the third meeting of the CEC analogue working group was ''How can analogue data be used for performance assessments, both in support of the results and for presentation to the public''. This report puts together the most recent achievements in this field, together with a review of on-going natural analogue programmes

  6. Induction of apoptosis in cholangiocarcinoma by an andrographolide analogue is mediated through topoisomerase II alpha inhibition.

    Science.gov (United States)

    Nateewattana, Jintapat; Dutta, Suman; Reabroi, Somrudee; Saeeng, Rungnapha; Kasemsook, Sakkasem; Chairoungdua, Arthit; Weerachayaphorn, Jittima; Wongkham, Sopit; Piyachaturawat, Pawinee

    2014-01-15

    Cholangiocarcinoma (CCA), the common primary malignant tumor of bile duct epithelial cells, is unresponsive to most chemotherapeutic drugs. Diagnosis with CCA has a poor prognosis, and therefore urgently requires effective therapeutic agents. In the present study we investigated anti-cancer effects of andrographolide analogue 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) and its mechanism in human CCA cell line KKU-M213 derived from a Thai CCA patient. By 24h after exposure, the analogue 3A.1 exhibited a potent cytotoxic effect on KKU-M213 cells with an inhibition concentration 50 (IC50) of approximately 8.0µM. Analogue 3A.1 suppressed DNA topoisomerase II α (Topo II α) protein expression, arrested the cell cycle at sub G0/G1 phase, induced cleavage of DNA repair protein poly (ADP-ribose) polymerases-1 (PARP-1), and enhanced expression of tumor suppressor protein p53 and pro-apoptotic protein Bax. In addition, analogue 3A.1 induced caspase 3 activity and inhibited cyclin D1, CDK6, and COX-2 protein expression. These results suggest that andrographolide analogue 3A.1, a novel topo II inhibitor, has significant potential to be developed as a new anticancer agent for the treatment of CCA. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Synthesis of an Orthogonal Topological Analogue of Helicene

    DEFF Research Database (Denmark)

    Wixe, Torbjörn; Wallentin, Carl‐Johan; Johnson, Magnus T.

    2013-01-01

    The synthesis of an orthogonal topological pentamer analogue of helicene is presented. This analogue forms a tubular structure with its aromatic systems directed parallel to the axis of propagation, which creates a cavity with the potential to function as a host molecule. The synthetic strategy...

  8. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  9. Potential methane emission reductions for two manure treatment technologies.

    Science.gov (United States)

    VanderZaag, Andrew C; Baldé, Hambaliou; Crolla, Anna; Gordon, Robert J; Ngwabie, N Martin; Wagner-Riddle, Claudia; Desjardins, Ray; MacDonald, J Douglas

    2018-04-01

    The effect of two dairy manure treatments, solid-liquid separation (SLS) and anaerobic digestion (AD), on methane potential and the speed of production was evaluated. Assays were performed in the lab to measure methane (CH 4 ) production over 202 d from dairy manure samples taken before and after each treatment. Compared to raw manure, CH 4 emissions on a per-L basis were reduced 81% by SLS and 59% by AD, on average. The mean (SD) ultimate CH 4 emission potential (B 0 ) per kg of volatile solids (VS) was 247 (8) L CH 4  kg -1  VS for raw manure, 221 (9) L CH 4  kg -1  VS for separated liquid, and 160 (4) L CH 4  kg -1  VS for anaerobic digestate. Thus, SLS reduced the B 0 of the liquid fraction by 11% and AD reduced B 0 by up to 35% compared to raw manure. Manure treatment affected the speed of CH 4 production: SLS increased the CH 4 production rate and thus separated liquid manure was the fastest to produce 90% of the ultimate CH 4 production. Therefore, both the speed of degradation and B 0 should be considered when assessing these techniques for farm-scale manure storages, because actual emission reductions will depend on storage conditions.

  10. Natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.

    1986-01-01

    A Natural Analogue Working Group was established by the Commission of the European Communities in 1985. The purpose of this group is to bring together modellers with earth scientists and others, so that maximum benefit can be obtained from natural analogue studies with a view to safe geological disposal of radioactive waste. The first meeting of this group was held in Brussels from November 5 to 7, 1985. The discussions mainly concerned the identification of the modellers' needs and of the earth scientists' capacity to provide for them. Following the debates, a written statement was produced by the Group; this document forms the core of the present Report. Notes and outlines of many of the presentations made are grouped in four appendixes. The valuable contribution of all those involved in the meeting is gratefully acknowledged

  11. Quantum analogue computing.

    Science.gov (United States)

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  12. The Palmottu analogue project

    International Nuclear Information System (INIS)

    Ahonen, L.; Blomqvist, R.; Suksi, J.

    1993-01-01

    The report gives a summary of the results of investigations carried out in 1992 at the Palmottu natural analogue study site, which is a small U-Th mineralization in Nummi-Pusula, southwestern Finland. Additionally, the report includes several separate articles dealing with various aspects of the Palmottu Analogue Project: (1) deep groundwater flow, (2) interpretation of hydraulic connections, (3) characterization of groundwater colloids, (4) uranium mineral-groundwater equilibrium, (5) water-rock interaction and (6) modelling of in situ matrix diffusion. The Palmottu Analogue Project aims at a more profound understanding of radionuclide transport processes in fractured crystalline bedrock. The essential factors controlling transport are groundwater flow and interaction between water and rock. Accordingly, the study includes (1) structural interpretations partly based on geophysical measurements, (2) hydrological studies including hydraulic drill-hole measurements, (3) flow modelling, (4) hydrogeochemical characterization of groundwater, uranium chemistry and colloid chemistry, (5) mineralogical studies, (6) geochemical interpretation and modelling, (7) studies of radionuclide mobilization and retardation including matrix diffusion, and (8) modelling of uranium series data. Palaeohydrogeological aspects, due to the anticipated future glaciation of the Fennoscandian Shield, are of special interest. Quaternary sediments are studied to gain information on post-glacial migration in the overburden. (orig.)

  13. Treatment of systemic sclerosis: potential role for stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Wen Xiong

    2009-11-01

    Full Text Available Wen Xiong, Chris T DerkDivision of Rheumatology, Thomas Jefferson University, Philadelphia, PA, 19107, USAAbstract: Hematopoietic stem cell transplantation may “reset” the immune reconstitution and induce self tolerance of autoreactive lymphocytes, and has been explored in the treatments for systemic sclerosis. Phase I/II trials have shown a satisfactory risk benefit ratio. The true benefit will be identified by two ongoing prospective, randomized phase III trials. Multipotent mesenchymal stromal cells (MSCs possess antiproliferative, anti-inflammatory, and immunosuppressive properties. The use of MSCs has showed successful responses in patients with severe steroid-resistant acute graft versus host disease in phase II trials, and may be a potentially promising option for patients with systemic sclerosis.Keywords: scleroderma, systemic sclerosis, treatment, stem cells, transplant

  14. UFLC/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from Artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis.

    Science.gov (United States)

    Zhao, Yong; Geng, Chang-An; Ma, Yun-Bao; Huang, Xiao-Yan; Chen, Hao; Cao, Tuan-Wu; He, Kang; Wang, Hao; Zhang, Xue-Mei; Chen, Ji-Jun

    2014-10-28

    Hepatitis B induced by HBV is a serious health problem. Artemisia capillaris (Yin-Chen) has long been used to treat hepatitis in traditional Chinese medicine. Coumarins, flavonoids and organic acids were revealed as its hepatoprotective and choleretic components, but its anti-HBV active components remain unknown. This current study focused on its anti-HBV active constituents by various chromatographic methods. LC/MS and bioassay-guided fractionation on the active extract of Artemisia capillaris led to the isolation of nine chlorogenic acid analogues. Structures of the isolates were elucidated by MS/MS and NMR techniques. Anti-HBV assay was performed on HepG 2.2.15 cell line in vitro: reduction of HBsAg and HBeAg secretions was measured by an ELISA method; inhibition of HBV DNA replication was monitored by real-time quantitative PCR and cellular toxicity was assessed by a MTT method. The 90% ethanol extract of Artemisia capillaris (Fr. AC) showed significantly inhibitory activity on HBV DNA replication with an IC₅₀ value of 76.1 ± 3.9 μg/mL and low cytotoxic effects (SI>20.1). To clarify its active constituents, the extract was further separated into 3 sub-fractions (AC-1, AC-2 and AC-3), of which Fr. AC-2 was the most active fraction against HBeAg secretion and HBV DNA replication with IC50 values of 44.2 ± 2.8 and 23.2 ± 1.9 μg/mL. Nine chlorogenic acid analogues were detected from the active part (Fr. AC-2) by a LC/MS technique and further separated by a HPLC method. The isolates were determined as chlorogenic acid (1), cryptochlorogenic acid (2), neochlorogenic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), chlorogenic acid methyl ester (7), cryptochlorogenic acid methyl ester (8), neochlorogenic acid methyl ester (9). Compounds 1-6 possessed potent activity against HBV DNA replication with IC50 values in the range of 5.5 ± 0.9-13.7 ± 1.3 μM. Di-caffeoyl analogues (4-6) also exhibited activity

  15. Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

    Science.gov (United States)

    Lee, Jihyoun; Chatterjee, Dev Kumar; Lee, Min Hyuk; Krishnan, Sunil

    2014-01-01

    Despite remarkable achievements in the treatment of breast cancer, some obstacles still remain. Gold nanoparticles may prove valuable in addressing these problems owing to their unique characteristics, including their enhanced permeability and retention in tumor tissue, their light absorbance and surface plasmon resonance in near-infrared light, their interaction with radiation to generate secondary electrons, and their ability to be conjugated with drugs or other agents. Herein, we discuss some basic concepts of gold nanoparticles, and early results from studies regarding their use in breast cancer, including toxicity and side effects. We also discuss these particles’ potential clinical applications. PMID:24556077

  16. Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Fengyuan Li

    2016-01-01

    Full Text Available Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.

  17. Mapping Thermal Energy Resource Potentials from Wastewater Treatment Plants

    Directory of Open Access Journals (Sweden)

    Georg Neugebauer

    2015-09-01

    Full Text Available Wastewater heat recovery via heat exchangers and heat pumps constitutes an environmentally friendly, approved and economically competitive, but often underestimated technology. By introducing the spatial dimension in feasibility studies, the results of calculations change considerably. This paper presents a methodology to estimate thermal energy resource potentials of wastewater treatment plants taking spatial contexts into account. In close proximity to settlement areas, wastewater energy can ideally be applied for heating in mixed-function areas, which very likely have a continuous heat demand and allow for an increased amount of full-load hours compared to most single-use areas. For the Austrian case, it is demonstrated that the proposed methodology leads to feasible results and that the suggested technology might reduce up to 17% of the Austrian global warming potential of room heating. The method is transferrable to other countries as the input data and calculation formula are made available. A broad application of wastewater energy with regard to spatial structures and spatial development potentials can lead to (1 increasing energy efficiency by using a maximum of waste heat and (2 a significant reduction of (fossil energy consumption which results in a considerable reduction of the global warming potential of the heat supply (GWP if electricity from renewables is used for the operation of heat pumps.

  18. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Neil V. Klinger

    2016-01-01

    Full Text Available Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

  19. A silyl andrographolide analogue suppresses Wnt/β-catenin signaling pathway in colon cancer.

    Science.gov (United States)

    Reabroi, Somrudee; Chairoungdua, Arthit; Saeeng, Rungnapha; Kasemsuk, Teerapich; Saengsawang, Witchuda; Zhu, Weiming; Piyachaturawat, Pawinee

    2018-05-01

    Hyperactivation of Wnt/β-catenin signaling implicated in oncogenesis of colorectal cancer (CRC) is a potential molecular target for chemotherapy. An andrographolide analogue, 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) has previously been reported to be potently cytotoxic toward cancer cells by unknown molecular mechanisms. The present study explored the anti-cancer activity of analogue 3A.1 on Wnt/β-catenin signaling in colon cancer cells (HT29 cells) which were more sensitive to the others (HCT116 and SW480 cells). Analogue 3A.1 inhibited viability of HT29 cells with IC 50 value of 11.1 ± 1.4 μM at 24 h, which was more potent than that of the parent andrographolide. Analogue 3A.1 also suppressed the proliferation of HT29 cells and induced cell apoptosis in a dose-dependent manner. Its apoptotic activity was accompanied with increased expressions of proteins related to DNA damages; PARP-1 and γ-H2AX. In addition, analogue 3A.1 significantly inhibited T-cell factor and lymphoid enhancer factor (TCF/LEF) promoter activity of Wnt/β-catenin signaling. Accordingly, the expressions of Wnt target genes and β-catenin protein were suppressed. Moreover, analogue 3A.1 increased the activity of GSK-3β kinase, which is a negative regulator responsible for degradation of intracellular β-catenin. This mode of action was further supported by the absence of the effects after treatment with a GSK-3β inhibitor, and over-expression of a mutant β-catenin (S33Y). Our findings reveal, for the first time, an insight into the molecular mechanism of the anti-cancer activity of analogue 3A.1 through the inhibition of Wnt/β-catenin/GSK-3β pathway and provide a therapeutic potential of the andrographolide analogue 3A.1 in CRC treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Potential role of aromatase inhibitors in the treatment of endometriosis

    Directory of Open Access Journals (Sweden)

    Abu Hashim H

    2014-07-01

    Full Text Available Hatem Abu HashimDepartment of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, EgyptAbstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%–10% of reproductive-age women, with a prevalence of 5%–50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis

  1. Anaerobia Treatments of the domestic residual waters. Limitations potentialities

    International Nuclear Information System (INIS)

    Giraldo Gomez, Eugenio

    1993-01-01

    The quick growth of the Latin American cities has prevented that an appropriate covering of public services is achieved for the whole population, One of the undesirable consequences of this situation is the indiscriminate discharge from the domestic and industrial residual waters to the nearest bodies of water with its consequent deterioration and with disastrous consequences about the ecology and the public health. The developed countries have controlled this situation using systems of purification of the residual waters previously to their discharge in the receptor source. The same as the technology of the evacuation of the served waters, they have become numerous efforts for the application of the purification systems used in the countries developed to the socioeconomic, climatic and cultural conditions of our means. One of the results obtained in these efforts is the economic inability of the municipalities to pay the high investment costs and of operation of the traditional systems for the treatment of the residual waters. Contrary to another type of public services, the treatment of the residual waters needs of appropriate technological solutions for the Climatic and socioeconomic means of the developing countries, One of the technological alternatives for the purification of the residual waters that has had a great development in the last decades has been that of the biological treatments in t anaerobia ambient. The objective of this contribution is to present, to author's trial, the limitations and potentialities of this technology type with special emphasis in the case of the domestic residual waters

  2. The potential role of cannabinoids in epilepsy treatment.

    Science.gov (United States)

    De Caro, Carmen; Leo, Antonio; Citraro, Rita; De Sarro, Caterina; Russo, Roberto; Calignano, Antonio; Russo, Emilio

    2017-11-01

    Epilepsy is one of the world's oldest recognized and prevalent neurological diseases. It has a great negative impact on patients' quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs' side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention. Areas covered: This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system. Expert commentary: Despite the fact that cannabis has been used for many purposes over 4 millennia, the development of drugs based on cannabinoids has been very slow. Only recently, research has focused on their potential effects and CBD is the first treatment of this group with clinical evidence of efficacy in children with Dravet syndrome; moreover, other studies are currently ongoing to confirm its effectiveness in patients with epilepsy. On the other hand, it will be of interest to understand whether drugs acting on the endocannabinoid system will be able to reach the market and prove their known preclinical efficacy also in patients with epilepsy.

  3. Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Lundby-Christensen, Louise; Vaag, Allan; Tarnow, Lise

    2016-01-01

    OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark....... PARTICIPANTS AND INTERVENTIONS: Participants with type 2 diabetes (glycated haemoglobin (HbA1c)≥7.5% (≥58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1-3 times daily (n=137) versus insulin aspart 3 times daily...

  4. From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis.

    Science.gov (United States)

    Devine, William G; Diaz-Gonzalez, Rosario; Ceballos-Perez, Gloria; Rojas, Domingo; Satoh, Takashi; Tear, Westley; Ranade, Ranae M; Barros-Álvarez, Ximena; Hol, Wim G J; Buckner, Frederick S; Navarro, Miguel; Pollastri, Michael P

    2017-03-10

    Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high-throughput screen of >42,000 compounds as a highly potent and fast-acting trypanocidal agent capable of curing a bloodstream infection of Trypanosoma brucei in mice. We have designed a library of analogues to probe the structure-activity relationship and improve the predicted central nervous system (CNS) exposure of NEU-1053. We report the activity of these inhibitors of T. brucei, the efficacy of NEU-1053 in a murine CNS model of infection, and identification of the target of NEU-1053 via X-ray crystallography.

  5. Potential of Using Solar Energy for Drinking Water Treatment Plant

    Science.gov (United States)

    Bukhary, S. S.; Batista, J.; Ahmad, S.

    2016-12-01

    Where water is essential to energy generation, energy usage is integral to life cycle processes of water extraction, treatment, distribution and disposal. Increasing population, climate change and greenhouse gas production challenges the water industry for energy conservation of the various water-related operations as well as limiting the associated carbon emissions. One of the ways to accomplish this is by incorporating renewable energy into the water sector. Treatment of drinking water, an important part of water life cycle processes, is vital for the health of any community. This study explores the feasibility of using solar energy for a drinking water treatment plant (DWTP) with the long-term goal of energy independence and sustainability. A 10 MGD groundwater DWTP in southwestern US was selected, using the treatment processes of coagulation, filtration and chlorination. Energy consumption in units of kWh/day and kWh/MG for each unit process was separately determined using industry accepted design criteria. Associated carbon emissions were evaluated in units of CO2 eq/MG. Based on the energy consumption and the existing real estate holdings, the DWTP was sized for distributed solar. Results showed that overall the motors used to operate the pumps including the groundwater intake pumps were the largest consumers of energy. Enough land was available around DWTP to deploy distributed solar. Results also showed that solar photovoltaics could potentially be used to meet the energy demands of the selected DWTP, but warrant the use of a large storage capacity, and thus increased costs. Carbon emissions related to solar based design were negligible compared to the original case. For future, this study can be used to analyze unit processes of other DWTP based on energy consumption, as well as for incorporating sustainability into the DWTP design.

  6. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    acids, $g(b)-amino acids and/or longer chain $g(v)-amino acids, and a difunctional group which preferably is a cyclic entity, in particular, an aromatic or heteroaromatic entity acting as an intercalator group. Specific compounds and a library of such compounds may be prepared using conventional solid......The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g(a)-amino...

  7. Cannabinoids: is there a potential treatment role in epilepsy?

    Science.gov (United States)

    Blair, Robert E; Deshpande, Laxmikant S; DeLorenzo, Robert J

    2015-01-01

    Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management. While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established. This commentary will touch on our understanding of the brain endocannabinoid system's regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures. At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy.

  8. Cannabidiol as potential treatment in refractory pediatric epilepsy.

    Science.gov (United States)

    Paolino, Maria Chiara; Ferretti, Alessandro; Papetti, Laura; Villa, Maria Pia; Parisi, Pasquale

    2016-01-01

    In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs (AEDs) alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.

  9. Autophagy as a potential target for sarcoma treatment.

    Science.gov (United States)

    Min, Li; Choy, Edwin; Pollock, Raphael E; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

    2017-08-01

    Autophagy is a constitutively active, evolutionary conserved, catabolic process for maintaining homeostasis in cellular stress responses and cell survival. Although its mechanism has not been fully illustrated, recent work on autophagy in various types of sarcomas has demonstrated that autophagy exerts an important role in sarcoma cell growth and proliferation, in pro-survival response to therapies and stresses, and in therapeutic resistance of sarcoma. Thus, the autophagic process is being seen as a possibly novel therapeutic target of sarcoma. Additionally, some co-regulators of autophagy have also been investigated as promising biomarkers for the diagnosis and prognosis of sarcoma. In this review, we summarize contemporary advances in the role of autophagy in sarcoma and discuss the potential of autophagy as a new target for sarcoma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Tolvaptan and its potential in the treatment of hyponatremia

    Directory of Open Access Journals (Sweden)

    Y Howard Lien

    2008-10-01

    Full Text Available Megan B Dixon, Y Howard LienDepartment of Medicine, University of Arizona, Arizona Kidney Disease and Hypertension Center, Tucson, Arizona, USAAbstract: Tolvaptan is a selective arginine vasopressin (AVP V2 receptor blocker used to induce free water diuresis in the treatment of euvolemic or hypervolemic hyponatremia. Currently the orally active medication is in the final stages prior to approval by the FDA for outpatient therapy. It appears to be safe and effective at promoting aquaresis and raising serum sodium levels in both short- and long-term studies. Tolvaptan is also effective for treatment of congestive heart failure (CHF exacerbation, but whether there are long standing beneficial effects on CHF is still controversial. Prolonged use of tolvaptan leads to increased endogenous levels of AVP and perhaps over-stimulation of V1A receptors. Theoretically this activation could lead to increased afterload and cardiac myocyte fibrosis, causing progression of CHF. However, after 52 weeks of tolvaptan therapy there was no worsening of left ventricular dilatation. In addition, tolvaptan is metabolized by the CYP3A4 system; thus physicians should be aware of the potential for increased interactions with other medications. Tolvaptan is a breakthrough in the therapy of hyponatremia as it directly combats elevated AVP levels associated with the syndrome of inappropriate secretion of antidiuretic hormone, congestive heart failure, and cirrhosis of the liver.Keywords: hyponatremia, arginine vasopressin, vasopressin receptors, syndrome of inappropriate antidiuretic hormone, congestive heart failure, liver cirrhosis

  11. Transaxial analogue tomography

    International Nuclear Information System (INIS)

    Duinker, S.; Geluk, R.J.; Mulder, H.

    1978-01-01

    After an introduction on computerized tomography (CT) scanners summarizing the various generations, the general outline of the concept of a transaxial tomography system is given, which is entirely based on analogue instead of digital techniques (AT system). In particular, the use of X-ray image-intensifier systems as a means of detecting the transmission profiles of the object in a so-called half-field detection method are discussed as well as various possibilities of detector scanning. It is further discussed how in a purely electronic way with the aid of a scan-converter, density profiles representative of parallel beams can be derived from the family of profiles as obtained from the fan-shaped beams in the actual experiment. A practical opto-electronic solution of the analogue spatial filtering problem is described as to how to process, on a real-time basis, parallel density profiles so that after back-projection tomographic images which are free from point-spreading effects will be obtained. Finally, after a brief indication of certain technical details for which corrective measures have to be worked out in the course of practical realization, the main relative advantages of AT scanners in comparison to CT scanners are enumerated. (Auth.)

  12. Evaluating Zeta Potential and the Calcite/Aragonite Ratio as Potential Success Indicators for Magnetic Water Treatment

    National Research Council Canada - National Science Library

    Lambert, Kevin

    1999-01-01

    The potential benefits of anti-scale magnetic treatment (AMT) are not realized or reliably predicted because the factors measuring performance of magnetic treatment have either not been identified or are poorly defined...

  13. Endocannabinoid system: potential novel targets for treatment of schizophrenia.

    Science.gov (United States)

    Saito, Atsushi; Ballinger, Michael D L; Pletnikov, Mikhail V; Wong, Dean F; Kamiya, Atsushi

    2013-05-01

    Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)-mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3.

    Science.gov (United States)

    Jbara, Muhammad; Guttmann-Raviv, Noga; Maity, Suman Kumar; Ayoub, Nabieh; Brik, Ashraf

    2017-09-15

    Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9. Herein we applied convergent total chemical protein synthesis to prepare trimethylated H3 at Lys79 to perform initial studies related to the regulation of this mark. Our study enabled us to identify KDM4D lysine demethylase as a potential regulator for trimethylated H3 at Lys79. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

    KAUST Repository

    Hasan, Mohammed Nihal

    2018-02-09

    Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

  16. Somatostatin analogues for acute bleeding oesophageal varices

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C.; Hrobjartsson, A.

    2008-01-01

    BACKGROUND: Somatostatin and its derivatives are sometimes used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver. OBJECTIVES: To study whether somatostatin or its analogues improve survival or reduce the need for blood transfusions in patients...... with bleeding oesophageal varices. SEARCH STRATEGY: PubMed and The Cochrane Library were searched (November 2007). Reference lists of publications, contacts with authors. SELECTION CRITERIA: All randomised trials comparing somatostatin or analogues with placebo or no treatment in patients suspected of acute...... or recent bleeding from oesophageal varices. DATA COLLECTION AND ANALYSIS: The outcome measures extracted were: mortality, blood transfusions, use of balloon tamponade, initial haemostasis and rebleeding. Intention-to-treat analyses including all randomised patients were conducted if possible; a random...

  17. Alligator Rivers analogue project

    International Nuclear Information System (INIS)

    Duerden, P.

    1990-01-01

    Australian Nuclear Science and Technology Organization has extensively evaluated uranium ore bodies in the Alligator Rivers Uranium Province in Australia as analogues of radioactive waste repositories. The work was extended for a three-year program as an international project based on the Koongarra uranium deposit and sponsored by the OECD Nuclear Energy Agency. The technical program comprises six major sub-projects involving modelling and experimental work: modelling of radionuclide migration; hydrogeology of the Koongarra uranium deposit; uranium/thorium series disequilibria studies; groundwater and colloid studies; fission product studies; transuranic nuclide studies; an outline of the technical programs and a summary of progress in the technical sub-projects is given. This is followed by a series of technical reports which briefly describe current research tasks, and which have been separately indexed

  18. A Short Term Analogue Memory

    DEFF Research Database (Denmark)

    Shah, Peter Jivan

    1992-01-01

    A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...

  19. Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues

    DEFF Research Database (Denmark)

    Okunola-Bakara, Oluyomi; Cao, Jianjing; Kopajtic, Theresa

    2014-01-01

    2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil, (±)-1) is a unique dopamine uptake inhibitor that binds the dopamine transporter (DAT) differently than cocaine and may have potential for the treatment of psychostimulant abuse. To further investigate structural requirements for this divergent...... of the diphenyl rings of (±)-1 gave several amide analogues with improved binding affinity for DAT and robust selectivity over the serotonin transporter (SERT), whereas affinity improved at SERT over DAT for the p-halo-substituted amine analogues. Molecular docking studies, using a subset of analogues with DAT...... and SERT homology models, and functional data obtained with DAT (A480T) and SERT (T497A) mutants defined a role for TM10 in the substrate/inhibitor S1 binding sites of DAT and SERT....

  20. Bromelain: A potential strategy for the adjuvant treatment of periodontitis

    Directory of Open Access Journals (Sweden)

    Felipe Rodolfo Pereira da Silva

    2016-01-01

    Full Text Available Introduction: Bromelain, a mixture of proteases derived from different parts of pineapple, has been described to have therapeutic benefits in a diversity of inflammatory diseases. Such effects are associated to its proteolytic activity. As one of the most common and multifactorial diseases, periodontitis is a bacterial infection that results from the damage to the integrity of the tissues around the tooth, which includes gingiva, periodontal ligament, and alveolar bone. In periodontitis, the recruitment of defense cells occurs, which releases several pro-inflammatory cytokines. At elevated levels, they can potentiate the alveolar bone loss. Studies have been conducted trying to alleviate the damage to the periodontium, however, the regeneration of the periodontal tissues is still limited. The Hypotheses: Based on previous studies showing that bromelain can act by decreasing the periodontal microorganism growth by proteolytically cleaving important cell surface molecules in leucocytes, by reducing neutrophils migration to periodontal sites, by downregulating the inflammation mediator levels, and by decreasing alveolar bone loss in the periodontitis. Evaluation of the Hypothesis: In a first moment, to evaluate this hypothesis, could be used two animal models: the ligature or bacteria inoculation induced periodontitis. If studies using animal models show encouraging results, appropriate clinical trials should be designed to evaluate the effect of bromelain as a complementary treatment for periodontal disease in humans, during the active phase or after the healing phase of mechanical therapy could be tested; to conduct a placebo-controlled study where health and periodontitis patients could be used.

  1. Evaluating the cytotoxicity of flaxseed orbitides for potential cancer treatment

    Directory of Open Access Journals (Sweden)

    Denis P. Okinyo-Owiti

    2015-01-01

    Full Text Available Flaxseed as well as its oil component possess antitumor activities against different types of cancer and have been used by some patients as complementary and/or alternative medicine. Linoorbitides (LOBs are one family of flaxseed compounds that has implications for anticancer and antioxidant activity. The cytotoxicity of [1-9-NαC]-linusorb-B3 (LOB3, [1-9-NαC]-linusorb-B2 (LOB2, [1-9-NαC],[1-Rs,Ss-MetO]-linusorb-B2 ([MetO]-LOB2 and [1-8-NαC],[1-Rs,Ss-MetO]-linusorb-B1 ([MetO]-LOB1 was measured against human breast cancer Sk-Br-3 and MCF7 cell lines and melanoma A375 cell line. Overall cytotoxicity is cell-type specific. It scales as the hydrophobicity and concentration of the LOBs with the most abundant LOB3 being the most cytotoxic. Oral administration of LOB3 as a potential therapeutic agent might not be applicable as a much too high and/or frequent dose would be required to achieve a serum concentration of 400–500 μg/mL due to bioavailability and pharmacokinetic factors. However, LOB3 may be suitable for topical treatment formulations or as a lead compound in developing anticancer LOB derivatives.

  2. Review of Natural Compounds for Potential Skin Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tawona N. Chinembiri

    2014-08-01

    Full Text Available Most anti-cancer drugs are derived from natural resources such as marine, microbial and botanical sources. Cutaneous malignant melanoma is the most aggressive form of skin cancer, with a high mortality rate. Various treatments for malignant melanoma are available, but due to the development of multi-drug resistance, current or emerging chemotherapies have a relatively low success rates. This emphasizes the importance of discovering new compounds that are both safe and effective against melanoma. In vitro testing of melanoma cell lines and murine melanoma models offers the opportunity for identifying mechanisms of action of plant derived compounds and extracts. Common anti-melanoma effects of natural compounds include potentiating apoptosis, inhibiting cell proliferation and inhibiting metastasis. There are different mechanisms and pathways responsible for anti-melanoma actions of medicinal compounds such as promotion of caspase activity, inhibition of angiogenesis and inhibition of the effects of tumor promoting proteins such as PI3-K, Bcl-2, STAT3 and MMPs. This review thus aims at providing an overview of anti-cancer compounds, derived from natural sources, that are currently used in cancer chemotherapies, or that have been reported to show anti-melanoma, or anti-skin cancer activities. Phytochemicals that are discussed in this review include flavonoids, carotenoids, terpenoids, vitamins, sulforaphane, some polyphenols and crude plant extracts.

  3. Bacteriophages as Potential Treatment for Urinary Tract Infections.

    Science.gov (United States)

    Sybesma, Wilbert; Zbinden, Reinhard; Chanishvili, Nino; Kutateladze, Mzia; Chkhotua, Archil; Ujmajuridze, Aleksandre; Mehnert, Ulrich; Kessler, Thomas M

    2016-01-01

    Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming so that well-tolerated, highly effective therapeutic alternatives are urgently needed. To investigate the effect of bacteriophages on Escherichia coli and Klebsiella pneumoniae strains isolated from the urine of patients suffering from UTIs. Forty-one E. coli and 9 K. pneumoniae strains, isolated from the urine of patients suffering from UTIs, were tested in vitro for their susceptibility toward bacteriophages. The bacteriophages originated from either commercially available bacteriophage cocktails registered in Georgia or from the bacteriophage collection of the George Eliava Institute of Bacteriophage, Microbiology and Virology. In vitro screening of bacterial strains was performed by use of the spot-test method. The experiments were implemented three times by different groups of scientists. The lytic activity of the commercial bacteriophage cocktails on the 41 E. coli strains varied between 66% (Pyo bacteriophage) and 93% (Enko bacteriophage). After bacteriophage adaptation of the Pyo bacteriophage cocktail, its lytic activity was increased from 66 to 93% and only one E. coli strain remained resistant. One bacteriophage of the Eliava collection could lyse all 9 K. pneumoniae strains. Based on the high lytic activity and the potential of resistance optimization by direct adaption of bacteriophages as reported in this study, and in view of the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a promising treatment option for UTIs highly warranting randomized controlled trials.

  4. Reactivation of Hepatitis B Virus in Hematopoietic Stem Cell Transplant Recipients in Japan: Efficacy of Nucleos(tide Analogues for Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Shingo Nakamoto

    2014-11-01

    Full Text Available We retrospectively reviewed 413 recipients with hematologic malignancies who underwent hematopoietic stem cell transplantation (HSCT between June 1986 and March 2013. Recipients with antibody to hepatitis B core antigen (anti-HBc and/or to hepatitis B surface antigen (anti-HBs were regarded as experiencing previous hepatitis B virus (HBV infection. Clinical data of these recipients were reviewed from medical records. We defined ≥1 log IU/mL increase in serum HBV DNA from nadir as HBV reactivation in hepatitis B surface antigen (HBsAg-positive recipients, and also defined ≥1 log IU/mL increase or re-appearance of HBV DNA and/or HBsAg as HBV reactivation in HBsAg-negative recipients. In 5 HBsAg-positive recipients, 2 recipients initially not administered with nucleos(tide analogues (NUCs experienced HBV reactivation, but finally all 5 were successfully controlled with NUCs. HBV reactivation was observed in 11 (2.7% of 408 HBsAg-negative recipients; 8 of these were treated with NUCs, and fortunately none developed acute liver failure. In 5 (6.0% of 83 anti-HBc and/or anti-HBs-positive recipients, HBV reactivation occurred. None of 157 (0% recipients without HBsAg, anti-HBs or anti-HBc experienced HBV reactivation. In HSCT recipients, HBV reactivation is a common event in HBsAg-positive recipients, or in HBsAg-negative recipients with anti-HBc and/or anti-HBs. Further attention should be paid to HSCT recipients with previous exposure to HBV.

  5. Treatment Options for Ovarian Low Malignant Potential Tumors

    Science.gov (United States)

    ... tests or procedures are used for staging. Staging laparotomy (a surgical incision made in the wall of ... treatment. Two types of standard treatment are used: Surgery The type of surgery (removing the tumor in ...

  6. Treatment Option Overview (Ovarian Low Malignant Potential Tumors)

    Science.gov (United States)

    ... tests or procedures are used for staging. Staging laparotomy (a surgical incision made in the wall of ... treatment. Two types of standard treatment are used: Surgery The type of surgery (removing the tumor in ...

  7. Bacteriophages as Potential Treatment for Urinary Tract Infections

    Science.gov (United States)

    Sybesma, Wilbert; Zbinden, Reinhard; Chanishvili, Nino; Kutateladze, Mzia; Chkhotua, Archil; Ujmajuridze, Aleksandre; Mehnert, Ulrich; Kessler, Thomas M.

    2016-01-01

    Background: Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming so that well-tolerated, highly effective therapeutic alternatives are urgently needed. Objective: To investigate the effect of bacteriophages on Escherichia coli and Klebsiella pneumoniae strains isolated from the urine of patients suffering from UTIs. Material and methods: Forty-one E. coli and 9 K. pneumoniae strains, isolated from the urine of patients suffering from UTIs, were tested in vitro for their susceptibility toward bacteriophages. The bacteriophages originated from either commercially available bacteriophage cocktails registered in Georgia or from the bacteriophage collection of the George Eliava Institute of Bacteriophage, Microbiology and Virology. In vitro screening of bacterial strains was performed by use of the spot-test method. The experiments were implemented three times by different groups of scientists. Results: The lytic activity of the commercial bacteriophage cocktails on the 41 E. coli strains varied between 66% (Pyo bacteriophage) and 93% (Enko bacteriophage). After bacteriophage adaptation of the Pyo bacteriophage cocktail, its lytic activity was increased from 66 to 93% and only one E. coli strain remained resistant. One bacteriophage of the Eliava collection could lyse all 9 K. pneumoniae strains. Conclusions: Based on the high lytic activity and the potential of resistance optimization by direct adaption of bacteriophages as reported in this study, and in view of the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a promising treatment option for UTIs highly warranting randomized controlled trials. PMID:27148173

  8. Post-operative Pain Analysis between Single Visit and Two Visit Root Canal Treatments using Visual Analogue Scale: An In Vivo Study

    Directory of Open Access Journals (Sweden)

    Kavita Tarale

    2013-01-01

    Full Text Available The purpose of this clinical study was to evaluate post-operative pain, after root canal therapy, performed in one appointment versus two appointment using calcium hydroxide intracanal medicament. Study design: In this in-vivo study, 60 patients requiring root canal therapy on permanent 1st molars were included. Patients were randomly divided into two experimental and one control group. Group1: One visit therapy (n=20 Group2: Two visit therapy with 1 week of calcium hydroxide dressing (n=20 Group3(Control: Two visit therapy with 1 week of sterile dry cotton pellet dressing (n=20 Materials and method : The standard protocol for all the patients included local anaesthesia, isolation & access cavity preparation, chemomechanical preparation with Rotary Protaper NiTi instruments, and irrigation with 3% sodium hypochlorite, 17% EDTA, 0.9%saline and 2% chlorhexidine. Teeth in group1 (n=20 were obturated on the same appointment using single cone technique (6% gutta percha points and AH Plus sealer. Teeth in group 2(n=20 and group 3(n=20 were given a dressing of calcium hydroxide and dry cotton pellet respectively for a week followed by double seal with Cavit G and IRM. These teeth were obturated on the 2nd appointment using same material and techniques as in group 1. Teeth in all three groups were restored with dual cure composite resin. A modified Visual Analogue Scale was used to measure preoperative pain and postoperative pain after 6, 12, 24 & 48hrs interval. Statistical analysis was performed using an independent-sample t test. There was no statistically significant difference between groups at any of the four postoperative intervals. There was no significant difference among all the three groups studied after 12, 24hrs & 48hrs. Conclusion : Within the limitations of this in vivo study, it may be concluded that Single Visit Endodontics provides excellent results, if care in diagnosis and proper case selection is given importance. Calcium hydroxide

  9. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...... of CorA. METHODS: HC-CorA were quantified in paired samples of cord serum from newborns and serum from mothers (n = 69). RESULTS: The CorA-concentration was higher in cord serum (median = 380, range: 41-780 pmol/L) than in serum from the mothers (median = 160, range: 64-330 pmol/L), (p...-analysis showed CorA-peaks with retention times of 13.5, 14,5 and 16.5 min in samples from both the mother and cord serum. The peak with retention time 16.5 min constituted 24% (mother) and 45% (cord serum) of the total amount CorA, and eluted as does dicyanocobinamide. CONCLUSION: Our results support that Cor...

  10. Studies of natural analogues and geological systems

    International Nuclear Information System (INIS)

    Brandberg, F.; Grundfelt, B.; Hoeglund, L.; Skagius K.; Karlsson, F.; Smellie, J.

    1993-04-01

    This review has involved studies of natural analogues and natural geological systems leading to the identification and quantification of processes and features of importance to the performance and safety of repositories for radioactive waste. The features and processes selected for the study comprise general geochemical issues related to the performance of the near- and far-field, the performance and durability of construction materials and the effects of glaciation. For each of these areas a number of potentially important processes for repository performance have been described, and evidence for their existence, as well as quantification of parameters of models describing the processes have been sought from major natural analogue studies and site investigations. The review has aimed at covering a relatively broad range of issues at the expense of in-depth analysis. The quantitative data presented are in most cases compilations of data from the literature; in a few cases results of evaluations made within the current project are included

  11. Delineation of potential hot spots for hyperthermia treatment planning optimisation

    NARCIS (Netherlands)

    Wiersma, J.; van Wieringen, N.; Crezee, H.; van Dijk, J. D. P.

    2007-01-01

    The optimal feed parameters of the generators for a complex-phased hyperthermia array system consisting of 4, 8 or even more applicators cannot be found using only the expertise of the treatment staff or using the limited amount of field and temperature data obtained during treatment. A number of

  12. Potential of regenerative medicine for treatment of vitiligo patients

    Directory of Open Access Journals (Sweden)

    A. A. Kubanova

    2014-01-01

    Full Text Available The article presents a review of publishes sources on the efficacy of methods such as tissue engineering and cellular transplantation of autologous melanocytes for treatment of vitiligo patients. The article describes general principles of treatment and particular features of current melanocyte transplantation methods.

  13. Effect of post-mating GnRH analogue (buserelin) treatment on PGF2alpha release in ewes and ewe lambs.

    Science.gov (United States)

    Khan, T H; Beck, N F G; Mann, G E; Khalid, M

    2006-09-01

    The objectives of this study were to determine the effects of buserelin or saline treatment on ovarian function (Experiment 1), plasma PGFM concentrations and oxytocin stimulated prostaglandin F(2alpha) (PGF(2alpha)) release (Experiment 2) in ewe lambs and ewes. Welsh Halfbred ewes (n=26) and ewe lambs (n=24) were mated to vasectomised rams at synchronised oestrus and on Day 12 post-mating each animal was injected intramuscularly either normal saline or 4 microg buserelin. In Experiment 1, plasma progesterone and oestradiol concentrations were determined in samples collected by jugular venepuncture 1h before and at 0, 2, 4, 6, 8, 24, 48 and 72 h after treatment (n=7 per treatment group). Progesterone concentrations increased (Pewes than in ewe lambs but oestradiol levels were similar for both age groups. Ovulation rate, determined by laparoscopy on Day 14, was similar for both age groups (ewes 1.1; ewe lambs 1.0). Buserelin treatment induced accessory corpora lutea in ewes (4/7; 57%) but not in ewe lambs (0/7; 0%). In the Experiment 2, plasma PGFM concentrations were determined in samples collected at 20-min intervals for 6h on Day 14 and at 20-min intervals for 1h before and at 10-min intervals for 1h and then at 20-min intervals for a further 3h period after an intravenous injection of oxytocin (1IU/kg body weight) on Day 15 post-oestrus. In this experiment there were five ewe lambs and six ewes per treatment group. There was no effect of buserelin treatment or age on basal PGFM concentrations on either Day 14 or 15. Although peak PGFM concentrations tended to be lower in buserelin-treated animals, the difference was not significant (P>0.05). However, peak duration following oxytocin challenge on Day 15 post-mating was shorter (Pewes compared with control ewe lambs. In conclusion, buserelin treatment given on Day 12 post-oestrus enhances luteal function more in ewes than ewe lambs and after a transitory increase, reduces oestradiol concentrations in both ewes and

  14. Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution

    OpenAIRE

    John R. White; Marco A. Belmont; Chris D. Metcalfe

    2006-01-01

    Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the ...

  15. Heterocyclic Analogues of Modafinil as Novel, Atypical Dopamine Transporter Inhibitors.

    Science.gov (United States)

    Kalaba, Predrag; Aher, Nilima Y; Ilić, Marija; Dragačević, Vladimir; Wieder, Marcus; Miklosi, Andras G; Zehl, Martin; Wackerlig, Judith; Roller, Alexander; Beryozkina, Tetyana; Radoman, Bojana; Saroja, Sivaprakasam R; Lindner, Wolfgang; Gonzalez, Eduardo Perez; Bakulev, Vasiliy; Leban, Johann Jakob; Sitte, Harald H; Urban, Ernst; Langer, Thierry; Lubec, Gert

    2017-11-22

    Modafinil is a wake promoting compound with high potential for cognitive enhancement. It is targeting the dopamine transporter (DAT) with moderate selectivity, thereby leading to reuptake inhibition and increased dopamine levels in the synaptic cleft. A series of modafinil analogues have been reported so far, but more target-specific analogues remain to be discovered. It was the aim of this study to synthesize and characterize such analogues and, indeed, a series of compounds were showing higher activities on the DAT and a higher selectivity toward DAT versus serotonin and norepinephrine transporters than modafinil. This was achieved by substituting the amide moiety by five- and six-membered aromatic heterocycles. In vitro studies indicated binding to the cocaine pocket on DAT, although molecular dynamics revealed binding different from that of cocaine. Moreover, no release of dopamine was observed, ruling out amphetamine-like effects. The absence of neurotoxicity of a representative analogue may encourage further preclinical studies of the above-mentioned compounds.

  16. Unlock the thermogenic potential of adipose tissue: pharmacological modulation and implications for treatment of diabetes and obesity

    Directory of Open Access Journals (Sweden)

    Xiao-Rong ePeng

    2015-11-01

    Full Text Available Brown adipose tissue (BAT is considered an interesting target organ for the treatment of metabolic disease due to its high metabolic capacity. Non-shivering thermogenesis, once activated, can lead to enhanced partitioning and oxidation of fuels in adipose tissues, and reduce the burden of glucose and lipids on other metabolic organs such as liver, pancreas and skeletal muscle. Sustained long-term activation of BAT may also lead to meaningful bodyweight loss. In this review, we discuss three different drug classes (the thiazolidinedione (TZD class of PPAR agonists, 3 adrenergic receptor agonists and fibroblast growth factor 21 (FGF21 analogues that have been proposed to regulate BAT and beige recruitment or activation, or both, and which have been tested in both rodent and human. The learnings from these classes suggest that restoration of functional BAT and beige mass as well as improved activation might be required to fully realize the metabolic potential of these tissues. Whether this can be achieved without the undesired cardiovascular side-effects exhibited by the TZD PPAR agonists and 3 adrenergic receptor agonists remains to be resolved.

  17. The Role of Novel Substituted Diindolyl Methane Analogues in the Treatment of Triple-Negative and ErbB2-Positive Breast Cancer

    Science.gov (United States)

    2016-05-01

    DIM-10 liposomes: We have developed a CREKA (A tumor endothelial cell targeted peptide, cysteine– arginine – glutamic acid– lysine –alanine) coated...report (2014-2015) we have studied the novel mechanism of DIM analogs (DIM-C-pPhCO2Me and DIM-C-pPhCN) in the treatment of TNBC by antagonizing an

  18. Male Central Precocious Puberty: Serum Profile of Anti-Müllerian Hormone and Inhibin B before, during, and after Treatment with GnRH Analogue

    Directory of Open Access Journals (Sweden)

    Romina P. Grinspon

    2013-01-01

    Full Text Available We aimed to describe the functional changes of Sertoli cells, based on the measurement of serum anti-Müllerian hormone (AMH and inhibin B during treatment with GnRHa and after its withdrawal in boys with central precocious puberty. Six boys aged 0.8 to 5.5 yr were included. AMH was low at diagnosis in patients >1 yr but within the normal range in younger patients. AMH increased to normal prepubertal levels during treatment. After GnRHa withdrawal, AMH declined concomitantly with the rise in serum testosterone. At diagnosis, inhibin B was elevated and decreased throughout therapy, remaining in the upper normal prepubertal range. In patients with testicular volume above 4 mL AMH remained higher in spite of suppressed FSH. After treatment withdrawal, inhibin B rose towards normal pubertal levels. In conclusion, AMH did not decrease in patients <1 yr reflecting the lack of androgen receptor expression in Sertoli cells in early infancy. Serum inhibin B might result from the contribution of two sources: the mass of Sertoli cells and the stimulation exerted by FSH. Sertoli cell markers might provide additional tools for the diagnosis and treatment followup of boys with central precocious puberty.

  19. Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution

    Directory of Open Access Journals (Sweden)

    John R. White

    2006-01-01

    Full Text Available Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the soil. We review relevant laboratory research on these various mechanisms and provide data on the few studies that have examined wetland removal. There is a need to document the degree to which various pharmaceutical compounds are removed in full-scale treatment wetlands, as there is a paucity of data on overall pharmaceutical removal rates.

  20. Present municipal water treatment and potential removal methods

    International Nuclear Information System (INIS)

    Lee, S.Y.; White, S.K.; Bondietti, E.A.

    1982-01-01

    Uranium analyses of raw water, intermediate stage, and treated water samples from 20 municipal water treatment plants indicated that the present treatment practices were not effective in removing uranium from raw waters when the influent concentration was in the range of 0.1 to 16 μg/L uranium. Laboratory batch tests revealed that the water softening and coagulant chemicals commonly used were able to remove more than 90% of the dissolved uranium ( < 100 μg/L) in waters if an optimum pH and dosage were provided. Absorbents, titanium oxide and activated charcoal, were also effective in uranium removal under specific conditions. Strong base anion exchange resin was the most efficient uranium adsorbent, and an anion exchange column is a recommended option for the treatment of private well waters containing uranium at higher than desirable levels

  1. Female reproductive potential after treatment for Hodgkin's disease

    International Nuclear Information System (INIS)

    Horning, S.J.; Hoppe, R.T.; Kaplan, H.S.; Rosenberg, S.A.

    1981-01-01

    The probability of maintaining ovarian function, becoming pregnant, and delivering a normal child is important to young women anticipating successful therapy for Hodgkin's disease. In this study, reproductive function was retrospectively examined in 103 women 40 years old or younger who had undergone treatment for Hodgkin's disease with total-lymphoid irradiation (TLI) alone, combination chemotherapy, or combined TLI and chemotherapy. Infertility was directly related to gonadal exposure to therapy and to age at treatment. Twenty women became pregnant after receiving total-nodal irradiation or combination chemotherapy or both. No fetal wastage occurred, and no birth defects were seen in the 24 infants born to these women. Even after intensive treatment programs, women successfully treated for Hodgkin's disease have become pregnant and delivered phenotypically normal children

  2. Outpatient treatment costs and their potential impact on cancer care

    International Nuclear Information System (INIS)

    Isshiki, Takahiro

    2014-01-01

    Cancer creates a tremendous financial burden. Cancer-related costs are categorized into direct, indirect, and psychosocial costs. Although there have been many reports on medical care costs, which are direct, those on other costs are extremely scarce. We estimated travel time and costs required for cancer patients to receive outpatient treatment. We studied 521 cancer patients receiving anti-cancer treatment between February 2009 and December 2012 at the Outpatient Chemotherapy Center of Teikyo University Chiba Medical Center. Address data were extracted from Data Warehouse electronic medical records, and travel distance and time required for outpatient treatment were calculated via MapInfo and ACT Distance Calculator Package. Transportation costs were estimated on the basis of ¥274 (=$3.00) per kilometer. The study design was approved by an ethics review board of Teikyo University (12-851). Average round-trip travel distance, time, and cost for all patients were 26.7 km, 72.5 min, and ¥7,303 ($79.99), respectively. Cancer patients incurred a travel cost of ¥4000–¥9000 ($40.00 to $100.00) for each outpatient treatment. With population aging, seniors living alone and senior households are increasing, and outpatient visits are becoming a common burden

  3. Mindful Music Listening as a Potential Treatment for Depression

    Science.gov (United States)

    Eckhardt, Kristen J.; Dinsmore, Julie A.

    2012-01-01

    Depression is one of the most common mental health issues. Although drug therapy and cognitive-behavioral therapy remain popular and effective treatments, alternative interventions such as the use of music listening and mindfulness practice as interventions during therapy have gained ground. Research on the use of music listening and mindfulness…

  4. Foraging at wastewater treatment works increases the potential for ...

    African Journals Online (AJOL)

    Wastewater treatment works (WWTWs) are known to provide profitable foraging areas for insectivorous bats in Europe and the New World because of their association with high abundance of pollution-tolerant midges (Diptera). However, bats that feed on these insects may also accumulate metal pollutants such as cadmium ...

  5. Anaerobic membrane bioreactors for wastewater treatment: feasibility and potential applications

    NARCIS (Netherlands)

    Jeison, D.A.

    2007-01-01

    Biomass retention is a necessary feature for the successful application of anaerobic digestion for wastewater treatment. Biofilms and granule formation are the traditional way to achieve such retention, enabling reactor operation at high biomass concentrations, and therefore at high organic loading

  6. Lipase-producing fungi for potential wastewater treatment and ...

    African Journals Online (AJOL)

    The use of fungal biomass as a lipase biocatalyst represents an attractive approach for the treatments of oil wastewater as well as for the production of biodiesel from oil and residual ... In this work, 20 filamentous fungi were isolated from the grease trap scum of a restaurant at the Federal University of Espírito Santo, Brazil.

  7. Lipase-producing fungi for potential wastewater treatment and ...

    African Journals Online (AJOL)

    Tuoyo Aghomotsegin

    2016-05-04

    May 4, 2016 ... The use of fungal biomass as a lipase biocatalyst represents an attractive approach for the treatments of oil wastewater as well as for the production of biodiesel from oil and residual grease, due to its greater stability, possibility of reuse, and lower cost. In this work, 20 filamentous fungi were isolated.

  8. Potential role of daratumumab in the treatment of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Khagi Y

    2014-06-01

    Full Text Available Yulian Khagi,1 Tomer M Mark21Department of Medicine, New York Presbyterian Hospital-Cornell Medical Center, New York, NY, USA; 2Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital-Cornell Medical Center, New York, NY, USAAbstract: Multiple myeloma is the second most common hematologic malignancy in the US. Treatments utilizing alkylating agents, corticosteroids, proteasome inhibitors, and immunomodulatory drugs have resulted in significant survival benefits, however, despite the advances, relapse is inevitable. Decreased depth and duration of response obtained with each successive relapse of disease is typical of the disease course, thereby highlighting a continuing need for new treatment options. With the introduction of monoclonal antibodies for multiple myeloma, new options for treatment in the relapsed setting are on the horizon. Among the new immunologic agents is daratumumab (DARA, a humanized antibody to CD38 with potent multifaceted antitumor activity. Phase I and II clinical trials have demonstrated significant reduction in serum M-protein and bone marrow plasma cell percentage in refractory patients, with an acceptable toxicity profile. Moreover, ex vivo studies have shown that DARA may be particularly useful in combination with currently used anti-myeloma agents. With a recent breakthrough drug designation by the US Food and Drug Administration, DARA shows promise as mono- and combination therapy for the treatment of relapsed/refractory multiple myeloma.Keywords: multiple myeloma, relapsed, refractory, monoclonal antibody, daratumumab, CD38

  9. GnRH analogue treatment on LH surge day 0 followed by single transvaginal artificial insemination with frozen semen on day 5 in bitches

    Science.gov (United States)

    OHTAKI, Tadatoshi; KOGA, Yasuna; ONO, Mamiko; WATANABE, Gen; TAYA, Kazuyoshi; TSUMAGARI, Shigehisa

    2014-01-01

    ABSTRACT Reproductive parameters were evaluated in 19 and 14 estrous beagles that received 100 µg of gonadotropin-releasing hormone (GnRH) and saline treatment, respectively, on the day of luteinizing hormone (LH) surge (Day 0; estimated by serial progesterone assay) and balloon catheter-aided single transvaginal artificial insemination of frozen semen on Day 5. Although the conception rate and litter size were similar between the GnRH and saline groups, the concentration of LH peak was significantly higher in GnRH-treated bitches (Pinsemination. PMID:25311914

  10. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas

    2007-01-01

    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis. Results In our final PK/PD model of the HPG...

  11. Endocannabinoid system: potential novel targets for treatment of schizophrenia

    OpenAIRE

    Saito, Atsushi; Ballinger, Michael; Pletnikov, Mikhail V.; Wong, Dean F.; Kamiya, Atsushi

    2012-01-01

    Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial prog...

  12. Approximate Treatment of the Dirac Equation with Hyperbolic Potential Function

    Science.gov (United States)

    Durmus, Aysen

    2018-03-01

    The time independent Dirac equation is solved analytically for equal scalar and vector hyperbolic potential function in the presence of Greene and Aldrich approximation scheme. The bound state energy equation and spinor wave functions expressed by the hypergeometric function have been obtained in detail with asymptotic iteration approach. In order to indicate the accuracy of this different approach proposed to solve second order linear differential equations, we present that in the non-relativistic limit, analytical solutions of the Dirac equation converge to those of the Schrödinger one. We introduce numerical results of the theoretical analysis for hyperbolic potential function. Bound states corresponding to arbitrary values of n and l are reported for potential parameters covering a wide range of interaction. Also, we investigate relativistic vibrational energy spectra of alkali metal diatomic molecules in the different electronic states. It is observed that theoretical vibrational energy values are consistent with experimental Rydberg-Klein-Rees (RKR) results and vibrational energies of NaK, K_2 and KRb diatomic molecules interacting with hyperbolic potential smoothly converge to the experimental dissociation limit D_e=2508cm^{-1}, 254cm^{-1} and 4221cm^{-1}, respectively.

  13. Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?

    Science.gov (United States)

    Li, Fengzhi; Jiang, Tao; Li, Qingyong; Ling, Xiang

    2017-01-01

    Camptothecin (CPT) was discovered from plant extracts more than 60 years ago. Since then, only two CPT analogues (irinotecan and topotecan) have been approved for cancer treatment, although several thousand CPT derivatives have been synthesized and many of them were actively studied in our research community over the past 6+ decades. In this review article, we briefly summarize: (1) the discovery and early development of CPTs, (2) the recognized CPT mechanism of action (MOA), (3) the synthesis of CPT and CPT analogues, and (4) the structure-activity relationship (SAR) of CPT and its analogues. Next, we provide evidence that certain CPT analogues can exert improved efficacy with low toxicity independently of topoisomerase I (Top1) inhibition; instead, these CPT analogues use novel MOAs by targeting important cancer survival-associated oncogenic proteins and/or by bypassing various treatment-resistant mechanisms. We then present a comprehensive review of the most advanced CPT analogues in clinical development, with the goal of resolving why no new CPTs have been FDA approved for cancer treatment, beyond irinotecan and topotecan. We argue that new CPT Top1 inhibitor drugs are unlikely being found to be significantly better than irinotecan and/or topotecan in terms of the overall antitumor activity and toxicity. The significance of CPT analogues that possess novel MOAs has not been sufficiently recognized so far. In our opinion, this is a research area with great potential to make a breakthrough for development of the next generation of CPT analogues that possess high efficacy (due to novel targets) and low toxicity (due to low inhibition of Top1 activity/function) for effective treatment of human disease, including cancer.

  14. Late effects of breast cancer treatment and potentials for rehabilitation

    DEFF Research Database (Denmark)

    Ewertz, Marianne; Jensen, Anders Bonde

    2011-01-01

    treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms......Abstract Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data...... from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement...

  15. Therapeutic potential of bimatoprost for the treatment of eyebrow hypotrichosis

    Directory of Open Access Journals (Sweden)

    Chanasumon N

    2018-02-01

    Full Text Available Nongsak Chanasumon, Tueboon Sriphojanart, Poonkiat Suchonwanit Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract: Eyebrows serve as a key feature of the face and have many roles, including cosmetic appearance and social communication. Eyebrow hypotrichosis, which refers to reduction or absence of the eyebrow hair, could be a major problem that leads to negative functional, psychological, and social consequences. Bimatoprost is an ophthalmic prostamide analog that is approved by the United States Food and Drug Administration for the treatment of eyelash hypotrichosis. Its proposed mechanism is stimulation of the prostaglandin receptor in dermal papilla and melanocyte, thus leading to a prolonged anagen phase and increased melanogenesis. The hair follicle then increases in thickness, length, and darkness. The efficacy of bimatoprost for the treatment of eyebrow hypotrichosis has been supported by well-controlled studies. Bimatoprost, which is noninvasive, effective, and well tolerated, is worth considering as a treatment option for eyebrow hypotrichosis. Keywords: bimatoprost, eyebrow, hair, hypotrichosis, prostaglandin, prostamide 

  16. Late effects of breast cancer treatment and potentials for rehabilitation

    International Nuclear Information System (INIS)

    Ewertz, Marianne; Bonde Jensen, Anders

    2011-01-01

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  17. Late effects of breast cancer treatment and potentials for rehabilitation

    Energy Technology Data Exchange (ETDEWEB)

    Ewertz, Marianne (Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark)); Bonde Jensen, Anders (Inst. of Clinical Research, Univ. of Southern Denmark (Denmark))

    2011-02-15

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  18. Retinal stem cells and potential cell transplantation treatments

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2014-11-01

    Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  19. Autophagy inhibitors as a potential antiamoebic treatment for Acanthamoeba keratitis.

    Science.gov (United States)

    Moon, Eun-Kyung; Kim, So-Hee; Hong, Yeonchul; Chung, Dong-Il; Goo, Youn-Kyoung; Kong, Hyun-Hee

    2015-07-01

    Acanthamoeba cysts are resistant to extreme physical and chemical conditions. Autophagy is an essential pathway for encystation of Acanthamoeba cells. To evaluate the possibility of an autophagic Acanthamoeba encystation mechanism, we evaluated autophagy inhibitors, such as 3-methyladenine (3MA), LY294002, wortmannin, bafilomycin A, and chloroquine. Among these autophagy inhibitors, the use of 3MA and chloroquine showed a significant reduction in the encystation ratio in Acanthamoeba cells. Wortmannin also inhibited the formation of mature cysts, while LY294002 and bafilomycin A did not affect the encystation of Acanthamoeba cells. Transmission electron microscopy revealed that 3MA and wortmannin inhibited autophagy formation and that chloroquine interfered with the formation of autolysosomes. Inhibition of autophagy or autolysosome formation resulted in a significant block in the encystation in Acanthamoeba cells. Clinical treatment with 0.02% polyhexamethylene biguanide (PHMB) showed high cytopathic effects on Acanthamoeba trophozoites and cysts; however, it also revealed high cytopathic effects on human corneal epithelial cells. In this study, we investigated effects of the combination of a low (0.00125%) concentration of PHMB with each of the autophagy inhibitors 3MA, wortmannin, and chloroquine on Acanthamoeba and human corneal epithelial cells. These new combination treatments showed low cytopathic effects on human corneal cells and high cytopathic effects on Acanthamoeba cells. Taken together, these results provide fundamental information for optimizing the treatment of Acanthamoeba keratitis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Emerging treatments for overactive bladder: clinical potential of botulinum toxins

    Directory of Open Access Journals (Sweden)

    Tincello DG

    2014-05-01

    Full Text Available Douglas G Tincello,1,2 Tina Rashid,2 Vladimir Revicky21Reproductive Sciences Section, Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK; 2Urogynecology Unit, Women's and Children's Clinical Business Unit, University Hospitals of Leicester National Health Service Trust, Leicester, UKAbstract: Overactive bladder (OAB is a symptom syndrome including urgency, frequency, and nocturia – with or without incontinence. It is a common manifestation of detrusor overactivity (DO. DO is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. OAB is, therefore, both a motor and sensory disorder. Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum and has been used in medicine for many years. Over the last 10 years, it has been used for the treatment of DO and OAB when standard treatments, such as bladder training and oral anticholinergic medication, have failed to provide symptom relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release from the neurons in the motor end plate and also at sensory synapses, although the clinical effect is not permanent due to the growth of new connections within treated tissues. It is known that botulinum toxin modulates vanillioid, purinergic, capsaicin, and muscarinic receptor expression within the lamina propria, returning them to levels seen in normal bladders. Clinically, the effect of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon the symptom of urgency, and also large effects on frequency, nocturia, leakage episodes, and continence rates. These effects have been seen consistently within eight randomized trials and numerous case series. Botulinum toxin appears safe, with the only common side effect being that of voiding difficulty, occurring in up to 10% of treated patients. Dosing regimens are variable, depending on

  1. CURCUMIN FOR ALZHEIMER’S DISEASE (AD) POTENTIAL TREATMENT

    OpenAIRE

    Sutiono, Dias Rima; Iasmartua, Steven

    2017-01-01

    Various studies had been conducted regarding the effect of curcumin on AD patients, thus, many of the studies had suggested that curcumin had the potential to prevent and treat AD through several molecular mechanisms including act as anti-inflammatory, anti-oxidant, binding the Aβ plaques, metal chelation, and lowering cholesterol level. One of the prominent characteristics of this neurodegenerative disease is shown by the presence of beta amyloids plaques (Aβ) and inflammation inside the pat...

  2. Glutamate receptor antagonists with the potential for migraine treatment.

    Science.gov (United States)

    Ferrari, Anna; Rustichelli, Cecilia; Baraldi, Carlo

    2017-12-01

    Preclinical, clinical, and other (e.g., genetic) evidence support the concept that migraine susceptibility may at least partially result from a glutamatergic system disorder. Therefore, the receptors of the glutamatergic system are considered relatively new targets for investigational drugs to treat migraine. Investigational and established glutamate receptor antagonists (GluRAs) have been shown to possess antinociceptive properties in preclinical models of trigeminovascular nociception and have been evaluated in clinical trials. This review focuses on preclinical and clinical studies of GluRAs for the treatment of migraine. Areas covered: A PubMed database search (from 1987 to December 2016) and a review of published studies on GluRAs in migraine were conducted. Expert opinion: All published clinical trials of investigational GluRAs have been unsuccessful in establishing benefit for acute migraine treatment. Clinical trial results contrast with the preclinical data, suggesting that glutamate (Glu) does not play a decisive role after the attack has already been triggered. These antagonists may instead be useful for migraine prophylaxis. Improving patient care requires further investigating and critically analyzing the role of Glu in migraine, designing experimental models to study more receptors and their corresponding antagonists, and identifying biomarkers to facilitate trials designed to target specific subgroups of migraine patients.

  3. Cannabidiol: a potential treatment for post Ebola syndrome?

    Science.gov (United States)

    Reznik, Sandra E; Gardner, Eliot L; Ashby, Charles R

    2016-11-01

    Patients recovered from Ebola virus infection may experience short- and long-term physical, neuropsychological and social sequelae, including arthralgia, musculoskeletal pain, ophthalmic inflammation, auditory problems, fatigue, confusion, insomnia, short-term memory impairment, anxiety, depression and anorexia, all lasting from two weeks to more than two years. Currently there are no treatments for post Ebola sequelae. We hypothesize that cannabidiol (CBD) may attenuate some of these post Ebola sequelae, several of which have been postulated to result from inflammation and/or an autoimmune response. CBD has anti-inflammatory actions in various animal models. Clinical studies have shown that oral administration of CBD, compared to placebo, significantly reduces anxiety, has antinociceptive and anticonvulsant actions, and may be therapeutic for insomnia. Overall, CBD has a number of pharmacological effects that may significantly improve the mental and somatic health of patients suffering from post Ebola sequelae. In humans, CBD, at therapeutic doses, does not: 1) elicit dependence or tolerance; 2) significantly alter heart rate or blood pressure; 3) affect gastrointestinal transit; 4) produce significant cognitive or psychomotor impairments. Mild sedation and nausea are the most commonly reported adverse effects associated with CBD.CBD, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post Ebola sequelae. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. GPR 120: The Potential Target for Obesity Treatment.

    Science.gov (United States)

    Tanagho, Peter A; Shohdy, Kyrillus S

    2016-01-01

    G protein coupled receptor 120 (GPR120) is a class of receptors in the gastrointestinal tract (GIT) that is implicated in nutrient sensing and body weight regulation. Functions of GPR120 are thought to be mediated by the release of a group of hormones known as incretins, such as glucagon like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). We have searched PubMed with the keywords "GPR120","GLP-1" and "obesity". Relevant studies were retrieved and included in the review. Recently, many exogenous compounds have been investigated in their role in the release of GLP-1 and in causing weight loss in obese rats. However, some results question the putative role of GPR120 in metabolic homeostasis. Herein, we evaluate the potential use of GPR120 as a target receptor in obesity and found it to be ubiquitous throughout the GIT, with various functions in each site. In order to find the optimal drug, the role of GPR120 in each site needs to be defined and selectivity of the potential drug needs to be studied to ensure the success of this growing line of obesity management.

  5. Therapeutic potential of kava in the treatment of anxiety disorders.

    Science.gov (United States)

    Singh, Yadhu N; Singh, Nirbhay N

    2002-01-01

    Anxiety disorders are among the most common psychiatric disorders that affect all age groups of the general population. Currently, the preferred treatment is with pharmacological drugs that have antidepressant or anti-anxiety properties. However, these agents have numerous and often serious adverse effects, including sedation, impaired cognition, ataxia, aggression, sexual dysfunction, tolerance and dependence. Withdrawal reactions on termination after long-term administration are also a major limiting factor in the use of these agents. Herbal remedies, including kava (Piper methysticum), have been shown to be effective as alternative treatments, at least in mild to moderate cases of anxiety. Kava is a social and ceremonial herb from the South Pacific. It is available in the west as an over-the-counter preparation. Its biological effects, due to a mixture of compounds called kavalactones, are reported to include sedative, anxiolytic, antistress, analgesic, local anaesthetic, anticonvulsant and neuroprotective properties. The pharmacological properties of kava are postulated to include blockade of voltage-gated sodium ion channels, enhanced ligand binding to gamma-aminobutyric acid (GABA) type A receptors, diminished excitatory neurotransmitter release due to calcium ion channel blockade, reduced neuronal reuptake of noradrenaline (norepinephrine), reversible inhibition of monoamine oxidase B and suppression of the synthesis of the eicosanoid thromboxane A(2), which antagonises GABA(A) receptor function. Clinical studies have shown that kava and kavalactones are effective in the treatment of anxiety at subclinical and clinical levels, anxiety associated with menopause and anxiety due to various medical conditions. Until recently, the adverse effects attributed to kava use were considered mild or negligible, except for the occurrence of a skin lesion. This disorder, called kava dermopathy, occurs only with prolonged use of large amounts of kava and is reversible on

  6. Drug delivery systems: Advanced technologies potentially applicable in personalized treatments.

    Science.gov (United States)

    Coelho, Jorge F; Ferreira, Paula C; Alves, Patricia; Cordeiro, Rosemeyre; Fonseca, Ana C; Góis, Joana R; Gil, Maria H

    2010-03-01

    Advanced drug delivery systems (DDS) present indubitable benefits for drug administration. Over the past three decades, new approaches have been suggested for the development of novel carriers for drug delivery. In this review, we describe general concepts and emerging research in this field based on multidisciplinary approaches aimed at creating personalized treatment for a broad range of highly prevalent diseases (e.g., cancer and diabetes). This review is composed of two parts. The first part provides an overview on currently available drug delivery technologies including a brief history on the development of these systems and some of the research strategies applied. The second part provides information about the most advanced drug delivery devices using stimuli-responsive polymers. Their synthesis using controlled-living radical polymerization strategy is described. In a near future it is predictable the appearance of new effective tailor-made DDS, resulting from knowledge of different interdisciplinary sciences, in a perspective of creating personalized medical solutions.

  7. Potential role of rilotumumab in the treatment of gastric cancer.

    Science.gov (United States)

    Waddell, Tom; Moorcraft, Sing Yu; Cunningham, David

    2014-01-01

    In 2014, outcomes for patients with advanced gastric cancer remain extremely poor with a high level of unmet need regarding effective therapeutic options. However, recent years have seen increasing interest in the role of the MET signaling pathway in this disease subtype, leading to the development and evaluation of MET-targeted therapeutics. Rilotumumab is a monoclonal antibody directed against hepatocyte growth factor, the only known ligand for the MET receptor. It is an unlicensed product which is currently undergoing evaluation in a randomized Phase III trial in 'MET-positive' gastric cancer. Here we discuss the background to the treatment of gastric cancer as well as the characteristics of rilotumumab and reported results with this agent in the trials performed to date.

  8. Interferons and their potential in the treatment of ocular inflammation

    Directory of Open Access Journals (Sweden)

    Friederike Mackensen

    2009-10-01

    Full Text Available Friederike Mackensen,1 Regina Max,2 Matthias D Becker31Department of Ophthalmology, 2Department of Internal Medicine, Interdisciplinary Uveitis Center, University of Heidelberg, Germany; 3Department of Ophthalmology, Triemli Hospital Zürich, SwitzerlandAbstract: Since their discovery in the 1950s interferons have been the scope of investigation in many diseases as therapeutic as well as pathogenetic factors. We know they have immune stimulatory and immune regulatory effects. This apparently counter-intuitive mechanism can be summarized as immunomodulatory action and seems to be very effective in a number of ocular inflammatory diseases. We review the current knowledge of interferons in immunity and autoimmunity and show their use in clinical ophthalmologic practice.Keywords: interferon, uveitis, treatment, inflammation

  9. ROS Modulator Molecules with Therapeutic Potential in Cancers Treatments.

    Science.gov (United States)

    Nicco, Carole; Batteux, Frédéric

    2017-12-31

    Reactive Oxygen Species (ROS) are chemically reactive chemical species containing oxygen. The redox status of a cell is function of the relative concentrations of oxidized and reduced forms of proteins, enzymes, ROS, molecules containing thiol and other factors. In the organism, the redox balance is based on the generation and elimination of ROS produced by endogenous and exogenous sources. All living organisms must maintain their redox equilibrium to survive and proliferate. Enzymatic and molecular pathways control ROS levels tightly but differentially depending on the type of cell. This review is an overview of various molecules that modulate ROS production/detoxification and have a synergistic action with the chemotherapies to kill cancer cells while preserving normal cells to avoid anticancer drugs side effects, allowing a better therapeutic index of the anticancer treatments.

  10. Angiogenic factors in preeclampsia: potential for diagnosis and treatment.

    Science.gov (United States)

    Goel, Arvind; Rana, Sarosh

    2013-11-01

    The review summarizes new observations of key roles for circulating angiogenic factors in diagnosing, managing, and treating preeclampsia. Alterations in circulating angiogenic factors (soluble fms-like tyrosine kinase-1 and placental growth factor) in preeclampsia correlate with the diagnosis and adverse outcomes, particularly when the disease presents prematurely (preeclampsia and its complications from other disorders that present with similar clinical profiles. A ratio of soluble fms-like tyrosine kinase-1/placental growth factor greater than 85 appears ideal as the cut-off for both diagnosis and prognosis. There is also evidence that modulating these factors has therapeutic effects, suggesting a future role for angiogenic factors in treatment and prevention of preeclampsia. Circulating angiogenic biomarkers help in diagnostic and prognostic profiling of preeclampsia and may facilitate better management of these patients.

  11. Introduction to electronic analogue computers

    CERN Document Server

    Wass, C A A

    1965-01-01

    Introduction to Electronic Analogue Computers, Second Revised Edition is based on the ideas and experience of a group of workers at the Royal Aircraft Establishment, Farnborough, Hants. This edition is almost entirely the work of Mr. K. C. Garner, of the College of Aeronautics, Cranfield. As various advances have been made in the technology involving electronic analogue computers, this book presents discussions on the said progress, including some acquaintance with the capabilities of electronic circuits and equipment. This text also provides a mathematical background including simple differen

  12. Modeling, synthesis and biological evaluation of potential retinoid X receptor (RXR) selective agonists: novel analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene).

    Science.gov (United States)

    Wagner, Carl E; Jurutka, Peter W; Marshall, Pamela A; Groy, Thomas L; van der Vaart, Arjan; Ziller, Joseph W; Furmick, Julie K; Graeber, Mark E; Matro, Erik; Miguel, Belinda V; Tran, Ivy T; Kwon, Jungeun; Tedeschi, Jamie N; Moosavi, Shahram; Danishyar, Amina; Philp, Joshua S; Khamees, Reina O; Jackson, Jevon N; Grupe, Darci K; Badshah, Syed L; Hart, Justin W

    2009-10-08

    This report describes the synthesis of analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), commonly known as bexarotene, and their analysis in acting as retinoid X receptor (RXR)-specific agonists. Compound 1 has FDA approval to treat cutaneous T-cell lymphoma (CTCL); however, its use can cause side effects such as hypothyroidism and increased triglyceride concentrations, presumably by disruption of RXR heterodimerization with other nuclear receptors. The novel analogues in the present study have been evaluated for RXR activation in an RXR mammalian-2-hybrid assay as well as an RXRE-mediated transcriptional assay and for their ability to induce apoptosis as well as for their mutagenicity and cytotoxicity. Analysis of 11 novel compounds revealed the discovery of three analogues that best induce RXR-mediated transcriptional activity, stimulate apoptosis, have comparable K(i) and EC(50) values to 1, and are selective RXR agonists. Our experimental approach suggests that rational drug design can develop new rexinoids with improved biological properties.

  13. Epigenetic Modifications and Potential New Treatment Targets in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Lorena Perrone

    2014-01-01

    Full Text Available Retinopathy is a debilitating vascular complication of diabetes. As with other diabetic complications, diabetic retinopathy (DR is characterized by the metabolic memory, which has been observed both in DR patients and in DR animal models. Evidences have provided that after a period of poor glucose control insulin or diabetes drug treatment fails to prevent the development and progression of DR even when good glycemic control is reinstituted (glucose normalization, suggesting a metabolic memory phenomenon. Recent studies also underline the role of epigenetic chromatin modifications as mediators of the metabolic memory. Indeed, epigenetic changes may lead to stable modification of gene expression, participating in DR pathogenesis. Moreover, increasing evidences suggest that environmental factors such as chronic hyperglycemia are implicated DR progression and may also affect the epigenetic state. Here we review recent findings demonstrating the key role of epigenetics in the progression of DR. Further elucidation of epigenetic mechanisms, acting both at the cis- and trans-chromatin structural elements, will yield new insights into the pathogenesis of DR and will open the way for the discovery of novel therapeutic targets to prevent DR progression.

  14. The potential for genetically altered microglia to influence glioma treatment.

    Science.gov (United States)

    Li, W; Holsinger, R M D; Kruse, C A; Flügel, A; Graeber, M B

    2013-09-01

    Diffuse and unstoppable infiltration of brain and spinal cord tissue by neoplastic glial cells is the single most important therapeutic problem posed by the common glioma group of tumors: astrocytoma, oligoastrocytoma, oligodendroglioma, their malignant variants and glioblastoma. These neoplasms account for more than two thirds of all malignant central nervous system tumors. However, most glioma research focuses on an examination of the tumor cells rather than on host-specific, tumor micro-environmental cells and factors. This can explain why existing diffuse glioma therapies fail and why these tumors have remained incurable. Thus, there is a great need for innovation. We describe a novel strategy for the development of a more effective treatment of diffuse glioma. Our approach centers on gaining control over the behavior of the microglia, the defense cells of the CNS, which are manipulated by malignant glioma and support its growth. Armoring microglia against the influences from glioma is one of our research goals. We further discuss how microglia precursors may be genetically enhanced to track down infiltrating glioma cells.

  15. Pharmacokinetics and tissue distribution of humanin and its analogues in male rodents.

    Science.gov (United States)

    Chin, Yung-Ping; Keni, Jyotsna; Wan, Junxiang; Mehta, Hemal; Anene, Francine; Jia, Yue; Lue, Yan-He; Swerdloff, Ronald; Cobb, Laura J; Wang, Christina; Cohen, Pinchas

    2013-10-01

    Humanin (HN) is a novel 24-amino acid mitochondrial-derived peptide that has demonstrated diverse cytoprotective effects, including an emerging role in diabetes. The purpose of this study was to examine the pharmacokinetics of humanin analogues, which show great potential as therapeutic agents (HNG and the non-IGFBP-3 binding, HNGF6A). 11-week-old male IGFBP-3(-/-) and wild type (WT) mice were divided into 3 groups: WT mice treated with HNG, WT mice treated with HNGF6A, and IGFBP-3(-/-) mice treated with HNG. Plasma was obtained from mice following ip injection with HN analogues, and HN levels were measured with ELISA. WT mice treated with HNGF6A and IGFBP-3(-/-) mice treated with HNG displayed a longer half-life of HN compared with WT mice treated with HNG. Following HNG injection, both IGF-1 and IGFBP-3 levels decreased over time. Adult male Sprague Dawley rats were also ip injected with HNG, and HN levels were measured in various tissues (plasma, liver, heart, and brain) by ELISA. The half-life of HN was found to be longer in rats compared with mice. In rats, HN levels were found to be highest in plasma, present in liver, and undetectable in brain or heart. The current study provides evidence of HN and IGFBP-3 association in the circulation and suggests that native HN may modulate the distribution of IGF-1 and IGFBP-3. The results also demonstrate varying kinetic profiles of HN analogues and interspecies variation in rodents. Sustainable levels of circulating HN measured in plasma underline the potential value of HN analogues as a new therapeutic intervention in the treatment of diabetes.

  16. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments.

    Science.gov (United States)

    Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

    2016-01-27

    Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an "ageist" approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.

  17. Glial Modulators as Potential Treatments of Psychostimulant Abuse

    Science.gov (United States)

    Beardsley, Patrick M.; Hauser, Kurt F.

    2014-01-01

    Glia (including astrocytes, microglia and oligodendrocytes), which constitute the majority of cells in the brain. have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mid-1800s, and only relatively recently have they been gaining their due respect. This development of appreciation has been nurtured by the growing awareness that drugs of abuse, including the psychostimulants, affect glial activity, and glial activity, in turn, has been found to modulate the effects of the psychostimulants. This developing awareness has begun to illuminate novel pharmacotherapeutic targets for treating psychostimulant abuse, for which targeting more conventional neuronal targets has not yet resulted in a single, approved medication. In this chapter, we discuss the molecular pharmacology, physiology and functional relationships that the glia have especially in the light in which they present themselves as targets for pharmacotherapeutics intended to treat psychostimulant abuse disorders. We then review a cross section of preclinical studies that have manipulated glial processes whose behavioral effects have been supportive of considering the glia as drug targets for psychostimulant-abuse medications. We then close with comments regarding the current clinical evaluation of relevant compounds for treating psychostimulant abuse, as well as the likelihood of future prospects. PMID:24484974

  18. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments

    Science.gov (United States)

    Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

    2016-01-01

    Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an “ageist” approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons. PMID:26828516

  19. Mesenchymal stem cells: potential in treatment of neurodegenerative diseases.

    Science.gov (United States)

    Tanna, Tanmay; Sachan, Vatsal

    2014-01-01

    Mesenchymal Stem Cells or Marrow Stromal Cells (MSCs) have long been viewed as a potent tool for regenerative cell therapy. MSCs are easily accessible from both healthy donor and patient tissue and expandable in vitro on a therapeutic scale without posing significant ethical or procedural problems. MSC based therapies have proven to be effective in preclinical studies for graft versus host disease, stroke, myocardial infarction, pulmonary fibrosis, autoimmune disorders and many other conditions and are currently undergoing clinical trials at a number of centers all over the world. MSCs are also being extensively researched as a therapeutic tool against neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD) and Multiple Sclerosis (MS). MSCs have been discussed with regard to two aspects in the context of neurodegenerative diseases: their ability to transdifferentiate into neural cells under specific conditions and their neuroprotective and immunomodulatory effects. When transplanted into the brain, MSCs produce neurotrophic and growth factors that protect and induce regeneration of damaged tissue. Additionally, MSCs have also been explored as gene delivery vehicles, for example being genetically engineered to over express glial-derived or brain-derived neurotrophic factor in the brain. Clinical trials involving MSCs are currently underway for MS, ALS, traumatic brain injuries, spinal cord injuries and stroke. In the present review, we explore the potential that MSCs hold with regard to the aforementioned neurodegenerative diseases and the current scenario with reference to the same.

  20. Bone loss following knee arthroplasty: potential treatment options.

    Science.gov (United States)

    Vasso, Michele; Beaufils, Philippe; Cerciello, Simone; Schiavone Panni, Alfredo

    2014-04-01

    The management of bone loss is a crucial aspect of the revision knee arthroplasty. Bone loss can hinder the correct positioning and alignment of the prosthetic components, and can prevent the achievement of a stable bone-implant interface. There is still controversy regarding the optimal management of knee periprosthetic bone loss, especially in large defects for which structural grafts, metal or tantalum augments, tantalum cones, porous metaphyseal sleeves, and special prostheses have been advocated. The aim of this review was to analyze all possible causes of bone loss and the most advanced strategies for managing bony deficiency within the knee joint reconstruction. Most significant and recent papers about the management of bone defects during revision knee arthroplasty were carefully analyzed and reviewed to report the most common causes of bone loss and the most effective strategies to manage them. Modular metal and tantalum augmentation showed to provide more stable and durable knee revisions compared to allografts, limited by complications such as graft failure, fracture and resorption. Moreover, modular augmentation may considerably shorten operative times with a potential decrease of complications, above all infection which has been frequently associated to the use of allografts. Modular augmentation may significantly reduce the need for allografting, whose complications appear to limit the long-term success of knee revisions.

  1. Hepcidin antagonists for potential treatments of disorders with hepcidin excess

    Directory of Open Access Journals (Sweden)

    Poli eMaura

    2014-04-01

    Full Text Available The discovery of hepcidin clarified the basic mechanism of the control of systemic iron homeostasis. Hepcidin is mainly produced by the liver as a propeptide and processed by furin into the mature active peptide. Hepcidin binds ferroportin, the only cellular iron exporter, causing the internalization and degradation of both. Thus hepcidin blocks iron export from the key cells for dietary iron absorption (enterocytes, recycling of haemoglobin iron (the macrophages and the release of storage iron from hepatocytes, resulting in the reduction of systemic iron availability. The BMP/HJV/SMAD pathway is the major regulator of hepcidin expression that responds to iron status. Also inflammation stimulates hepcidin via the IL6/STAT3 pathway with a support of an active BMP/HJV/SMAD pathway. In some pathological conditions hepcidin level is inadequately elevated and reduces iron availability in the body, resulting in anemia. These conditions occur in the genetic Iron Refractory Iron Deficiency Anemia (IRIDA and the common Anemia of Chronic Disease (ACD or Anemia of Inflammation. Currently, there is no definite treatment for ACD. Erythropoiesis stimulating agents and intravenous iron have been proposed in some cases but they are scarcely effective and may have adverse effects. Alternative approaches aimed to a pharmacological control of hepcidin expression have been attempted, targeting different regulatory steps. They include hepcidin sequestering agents (antibodies, anticalins and aptamers, inhibitors of BMP/SMAD or of IL6/STAT3 pathway or of hepcidin transduction (siRNA/shRNA or ferroportin stabilizers. In this review we summarized the biochemical interactions of the proteins involved in the BMP/HJV/SMAD pathway and its natural inhibitors, the murine and rat models with high hepcidin levels currently available and finally the progresses in the development of hepcidin antagonists, with particular attention to the role of heparins and heparin sulphate

  2. Pericyte: Potential Target for Hemorrhagic Stroke Prevention and Treatment.

    Science.gov (United States)

    Li, Qiang; Liu, Xin; Ruan, Huaizhen; Chen, Yujie; Feng, Hua

    2017-09-06

    Despite long-standing and worldwide efforts, hemorrhagic stroke remains a critical clinical syndrome that exerts a heavy toll on affected individuals and their families due to the lack of preventive and therapeutic targets. To clarify the pathogenesis of hemorrhagic stroke and to identify novel therapeutic targets. Targeting pericytes, the typical mural cells of microvessels, could serve as a way to modulate microvascular permeability, development, and maturation by regulating endothelial cell functions and modulating tissue fibrosis and inflammatory responses. Pericytes in hemorrhagic stroke may exert the following functions: before bleeding, the morphological aberration and dysfunction of pericytes may lead to aneurysm formation, angiopsathyrosis, and hemodynamic disturbances, ultimately causing vasculature rupture. In the acute phase after hemorrhage, pericytes are faced with a complicated bleeding environment, which results in the death of pericytes, blood-brain barrier damage, pericyte-mediated inflammatory cascades, white matter impairment, and ultimately aggravated neural injury. In the recovery period post-hemorrhage, in situ pericytes are activated and differentiate into neurons, glia and endothelial cells to repair the neural vascular network. Moreover, many pericytes are recruited to the lesion and contribute to blood-brain barrier remodeling, thus facilitating neurovascular functional recovery after stroke. Due to the multiple functions of pericytes in the development of vascular rupture and hemorrhagic stroke pathophysiology, additional drugs and trials targeting pericytes and evaluations of their effectiveness are required in future investigations to develop new strategies for the prevention and treatment of hemorrhagic stroke. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Isolation and structural identification of a novel minoxidil analogue in an illegal dietary supplement: triaminodil.

    Science.gov (United States)

    Lee, Ji Hyun; Park, Han Na; Park, Hyoung Joon; Kim, Nam Sook; Park, Sung-Kwan; Lee, Jongkook; Baek, Sun Young

    2018-01-01

    A new minoxidil analogue was detected in an illegal dietary supplement advertised as a hair-growth treatment. The analogue was identified using ultra-performance liquid chromatography (UPLC), high-resolution mass spectrometry (LC-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound was structurally elucidated as a minoxidil analogue in which the piperidinyl group of minoxidil was replaced with a pyrrolidinyl group corresponding to a molecular formula of C 8 H 13 N 5 O. The new analogue has been named triaminodil. As this is the first report of the compound, there are no chemical, toxicology or pharmacological data available.

  4. Superconductive analogue of spin glasses

    International Nuclear Information System (INIS)

    Feigel'man, M.; Ioffe, L.; Vinokur, V.; Larkin, A.

    1987-07-01

    The properties of granular superconductors in magnetic fields, namely the existence of a new superconductive state analogue of the low-temperature superconductive state in spin glasses are discussed in the frame of the infinite-range model and the finite-range models. Experiments for elucidation of spin-glass superconductive state in real systems are suggested. 30 refs

  5. Chemopreventive properties of curcumin analogues ...

    African Journals Online (AJOL)

    Chemopreventive properties of curcumin analogues, hexagamavunone-0 and gamavutone-0, in rat colorectal cancer model. ... Histopathological analysis was performed using H & E staining and immunohistochemistry with antibodies against adenomatous polyposis coli (APC) and cyclooxygenase 2 (COX-2). Results: All ...

  6. Synthesis of phosphono analogues of dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

    Science.gov (United States)

    Page, P; Blonski, C; Périé, J

    1999-07-01

    The present paper describes the synthetic routes of six phosphono analogues of dihydroxyacetone phosphate and five phosphono analogues of glyceraldehyde 3-phosphate through alpha-, beta- and gamma-hydroxyphosphonate esters precursors containing a protected carbonyl group. In some situations, depending on the sequence used for the deprotection of the phosphonate and carbonyl groups, the aldol/ketol rearrangement allowed the synthesis of either dihydroxyacetone phosphate or glyceraldehyde 3-phosphate analogues from the same precursors. All these analogues are of interest both as active-site probes and as potential substrates for glycolytic enzymes such as fructose 1,6-diphosphate aldolases (EC 4.1.2.13).

  7. Characterization of the Potential Hazards Associated with Potential RCRA Treatment Noncompliances

    Energy Technology Data Exchange (ETDEWEB)

    Clark, David Lewis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-08-20

    The purpose of this document is to provide a hazard evaluation of the noncompliances and whether any new actions are required to mitigate potential risk to the worker or the public. In short, we have reviewed the noncompliances and have concluded that the possibility of exothermic reactions leading to radioactive release is not credible, and in one case, inconceivable, stemming from the fact that the majority fraction of the waste is compatible with organic absorbents and neutralizers. It is not expected that the noncompliances would generate or produce uncontrolled flammable fumes, gases, extreme heat, pressure, fire, explosions, or violent reactions.

  8. Antineoplastic Activities of MT81 and Its Structural Analogue in Ehrlich Ascites Carcinoma-Bearing Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Sujata Maiti Choudhury

    2010-01-01

    Full Text Available Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p. at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST, increased life span (ILS, tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA and reduced glutathione (GSH content, and by the activity of superoxide dismutase (SOD and catalase (CA T. MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

  9. Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes.

    Science.gov (United States)

    Lambadiari, Vaia; Pavlidis, George; Kousathana, Foteini; Varoudi, Maria; Vlastos, Dimitrios; Maratou, Eirini; Georgiou, Dimitrios; Andreadou, Ioanna; Parissis, John; Triantafyllidi, Helen; Lekakis, John; Iliodromitis, Efstathios; Dimitriadis, George; Ikonomidis, Ignatios

    2018-01-08

    Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-Utw MVO ), at peak (%dpTw-Utw PEF ) and end of early LV diastolic filling (%dpTw-Utw EDF ) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP. After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-Utw MVO (31 ± 10 vs. 40 ± 14), %dpTw-Utw PEF (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = - 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations

  10. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    OpenAIRE

    Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

    2016-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

  11. Efficacy of Antimicrobials on Bacteria Cultured in a Spaceflight Analogue

    Science.gov (United States)

    Nickerson, CA; Wotring, Virginia; Barrila, Jennifer; Crabbe, Aurelie; Castro, Sarah; Davis, Richard; Rideout, April; McCarthy, Breanne; Ott, C. Mark

    2014-01-01

    . This study investigated the response of three medically significant microorganisms grown in the RWV to antibiotics that could be used on spaceflight missions. Our findings suggest potential alterations in antibiotic efficacy during spaceflight and indicate that future studies on the antibiotic response require additional basic research using the RWV and/or true spaceflight. However, while this analogue has reinforced these potential alterations, the results suggest the best approach for applied forward work is evaluating an in vivo system during spaceflight, including human and rodent studies. The complex nature of the analysis for many antibiotics and organism suggests the best approach to determine in vivo responses during pharmaceutical treatment is evaluating an in vivo system during spaceflight.

  12. A preliminary feasibility study on natural analogue in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chun Soo; Bae, Dae Seok; Kim, Kyung Su; Koh, Yong Kwon; Park, Byung Yun

    2000-03-01

    Preliminary study on the assessment of natural analogue study in Korea for the deep geological disposal of high-level radioactive waste was carried out. The project on natural analogue study in other countries are introduced. The uranium-bearing deposit in Okcheon belt are summarized, which reported to be uranium-bearing minerals in order to assess to feasibility for natural analogue study in Korea. Among the uranium-bearing deposits, the Deokpyeong area, reported to be the highest reservoir and grade, are selected as the study site, and the elementary investigation, including survey of radioactivity and geochemistry are carried out. According to the investigation of surface environment, the radioactivity and uranium content in the surface water and shallow groundwater does not show any anormal values. However, the radioactivity is expected to be increased in depth and the groundwater reacted with uranium-bearing graphite formation shows high unanium content, indicating the potential possibility for natural analogue study in Korea. In future, if more detail study are performed, the assessment of natural analogue study in Korea are expected.

  13. Novel acetylcholine and carbamoylcholine analogues

    DEFF Research Database (Denmark)

    Hansen, Camilla Petrycer; Jensen, Anders Asbjørn; Christensen, Jeppe K.

    2008-01-01

    A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity...... for this subtype over alpha 3beta 4, alpha 4beta 4, and alpha 7 nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced alpha 4beta 2 selectivities exhibited...... by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial alpha 4beta 2 nAChR agonist with negligible activities at the alpha 3beta 4 and alpha 7 subtypes, thus being one of the few truly functionally selective alpha 4beta 2 nACh...

  14. Psoralea glandulosa as a Potential Source of Anticancer Agents for Melanoma Treatment

    Directory of Open Access Journals (Sweden)

    Alejandro Madrid

    2015-04-01

    Full Text Available With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol (1, 3-hydroxy-bakuchiol (2 and 12-hydroxy-iso-bakuchiol (3 against melanoma cells (A2058. In addition, the effect in cancer cells of bakuchiol acetate (4, a semi-synthetic derivative of bakuchiol, was examined. The results obtained show that the resinous exudate inhibited the growth of cancer cells with IC50 value of 10.5 μg/mL after 48 h of treatment, while, for pure compounds, the most active was the semi-synthetic compound 4. Our data also demonstrate that resin is able to induce apoptotic cell death, which could be related to an overall action of the meroterpenes present. In addition, our data seem to indicate that the apoptosis correlated to the tested products appears, at least in part, to be associated with an increase of reactive oxygen species (ROS production. In summary, our study provides the first evidence that P. glandulosa may be considered a source of useful molecules in the development of analogues with more potent efficacy against melanoma cells.

  15. Psoralea glandulosa as a Potential Source of Anticancer Agents for Melanoma Treatment

    Science.gov (United States)

    Madrid, Alejandro; Cardile, Venera; González, César; Montenegro, Ivan; Villena, Joan; Caggia, Silvia; Graziano, Adriana; Russo, Alessandra

    2015-01-01

    With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol (1), 3-hydroxy-bakuchiol (2) and 12-hydroxy-iso-bakuchiol (3)) against melanoma cells (A2058). In addition, the effect in cancer cells of bakuchiol acetate (4), a semi-synthetic derivative of bakuchiol, was examined. The results obtained show that the resinous exudate inhibited the growth of cancer cells with IC50 value of 10.5 μg/mL after 48 h of treatment, while, for pure compounds, the most active was the semi-synthetic compound 4. Our data also demonstrate that resin is able to induce apoptotic cell death, which could be related to an overall action of the meroterpenes present. In addition, our data seem to indicate that the apoptosis correlated to the tested products appears, at least in part, to be associated with an increase of reactive oxygen species (ROS) production. In summary, our study provides the first evidence that P. glandulosa may be considered a source of useful molecules in the development of analogues with more potent efficacy against melanoma cells. PMID:25860949

  16. Substrate analogues for isoprenoid enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  17. Environmental Life Cycle Assessment and Cost Analysis of Bath, NY Wastewater Treatment Plant: Potential Upgrade Implications

    Science.gov (United States)

    Many communities across the U.S. are required to upgrade wastewater treatment plants (WWTP) to meet increasingly stringent nutrient effluent standards. However, increased capital, energy and chemical requirements of upgrades create potential trade-offs between eutrophication pot...

  18. Potential impact of diet on treatment effect from anti-TNF drugs in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

    2017-01-01

    We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest...... inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted....

  19. Climate Analogues for agricultural impact projection and adaptation – a reliability test

    Directory of Open Access Journals (Sweden)

    Swen P.M. Bos

    2015-10-01

    Full Text Available The climate analogue approach is often considered a valuable tool for climate change impact projection and adaptation planning, especially for complex systems that cannot be modelled reliably. Important examples are smallholder farming systems using agroforestry or other mixed-cropping approaches. For the projected climate at a particular site of interest, the analogue approach identifies locations where the current climate is similar to these projected conditions. By comparing baseline-analogue site pairs, information on climate impacts and opportunities for adaptation can be obtained. However, the climate analogue approach is only meaningful, if climate is a dominant driver of differences between baseline and analogue site pairs. For a smallholder farming setting on Mt. Elgon in Kenya, we tested this requirement by comparing yield potentials of maize and coffee (obtained from the IIASA Global Agro-ecological Zones dataset among 50 close analogue sites for different future climate scenarios and models, and by comparing local ecological knowledge and farm characteristics for one baseline-analogue pair.Yield potentials among the 50 closest analogue locations varied strongly within all climate scenarios, hinting at factors other than climate as major drivers of what the analogue approach might interpret as climate effects. However, on average future climatic conditions seemed more favourable to maize and coffee cultivation than current conditions. The detailed site comparison revealed substantial differences between farms in important characteristics, such as farm size and presence of cash crops, casting doubt on the usefulness of the comparison for climate change analysis. Climatic constraints were similar between sites, so that no apparent lessons for adaptation could be derived. Pests and diseases were also similar, indicating that climate change may not lead to strong changes in biotic constraints at the baseline site in the near future. From

  20. Nucleic acid toolkit: Potential diagnosis and treatment of major infectious diseases endemic in developing countries

    CSIR Research Space (South Africa)

    Millroy, L

    2011-09-01

    Full Text Available provides insights into their current diagnostics and treatments and the future prospects. In particular, the book highlights the use of nucleic acid therapies and focuses on the use of aptamers as potential treatment and diagnostic tools for these diseases...

  1. The potential use of ionising energy treatment in Queensland's horticultural industries

    International Nuclear Information System (INIS)

    Heather, N.W.; Sheehy, P.T.; Muirhead, I.F.; Brown, B.I.; Hassall, R.N.

    1985-01-01

    The potential application of ionising energy treatment technology in Queensland falls into three categories: insect disinfestation, disease control and quality improvement. The technology fulfils the requirements of a disinfestation treatment against Queensland fruit fly and other pests of quarantine importance in respect to efficacy, absence of phytotoxicity, absence of residues and, on technical considerations would be an ideal replacement for the fumigant EDB. The report examines the purposes of ionising energy treatment, economic and marketing aspects and research needs

  2. Potential Bacterial Consortium to Increase the Effectiveness of Beer Wastewater Treatment

    OpenAIRE

    Putu Nia Anggraeni; Ida Bagus Wayan Gunam; Retno Kawuri

    2014-01-01

    The main objective of this research is to determine the effectiveness of microbial consortia in beer wastewater treatment. The research was initiated with the isolation of soil microbial consortium that has been contaminated by beer waste water, followed by the selection of the best potential microbial beer wastewater treatment. At the end, the selection of the best microbial consortium was tested in beer wastewater treatment based on pollutant parameters namely biochemical oxygen demand (BOD...

  3. Synthesis and Biological Investigation of Δ(12)-Prostaglandin J3 (Δ(12)-PGJ3) Analogues and Related Compounds.

    Science.gov (United States)

    Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Heretsch, Philipp; Yu, Ruocheng; Grove, Charles I; Hale, Christopher R H; ElMarrouni, Abdelatif; Fetz, Verena; Brönstrup, Mark; Aujay, Monette; Sandoval, Joseph; Gavrilyuk, Julia

    2016-05-25

    A series of Δ(12)-prostaglandin J3 (Δ(12)-PGJ3) analogues and derivatives were synthesized employing an array of synthetic strategies developed specifically to render them readily available for biological investigations. The synthesized compounds were evaluated for their cytotoxicity against a number of cancer cell lines, revealing nanomolar potencies for a number of them against certain cancer cell lines. Four analogues (2, 11, 21, and 27) demonstrated inhibition of nuclear export through a covalent addition at Cys528 of the export receptor Crm1. One of these compounds (i.e., 11) is currently under evaluation as a potential drug candidate for the treatment of certain types of cancer. These studies culminated in useful and path-pointing structure-activity relationships (SARs) that provide guidance for further improvements in the biological/pharmacological profiles of compounds within this class.

  4. Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer

    Science.gov (United States)

    2006-06-01

    product analogs. J Am Chem Soc 1978; 100: 2551–2553. 39 Burri C, Brun R. Eflornithine for the treatment of human African trypanosomiasis . Parasitol Res...ototoxicity) at high therapeutic doses [29]. Currently, DFMO is the front-line agent in the treatment of African trypanosomiasis and is undergoing...Polyamine Analogues in Human Breast Cancer. PRINCIPAL INVESTIGATOR: Yi Huang, M.D., Ph.D. CONTRACTING ORGANIZATION: Johns

  5. Potential treatment options and future research to increase hepatitis C virus treatment response rate.

    Science.gov (United States)

    Tencate, Veronica; Sainz, Bruno; Cotler, Scott J; Uprichard, Susan L

    2010-10-01

    Hepatitis C virus (HCV) is a liver-tropic blood-borne pathogen that affects more than 170 million people worldwide. Although acute infections are usually asymptomatic, up to 90% of HCV infections persist with the possibility of long-term consequences such as liver fibrosis, cirrhosis, steatosis, insulin resistance, or hepatocellular carcinoma. As such, HCV-associated liver disease is a major public health concern. Although the currently available standard of care therapy of pegylated interferon α plus ribavirin successfully treats infection in a subset of patients, the development of more effective, less toxic HCV antivirals is a health care imperative. This review not only discusses the limitations of the current HCV standard of care but also evaluates upcoming HCV treatment options and how current research elucidating the viral life cycle is facilitating the development of HCV-specific therapeutics that promise to greatly improve treatment response rates both before and after liver transplantation.

  6. Wastewater Treatment Energy Recovery Potential For Adaptation To Global Change: An Integrated Assessment.

    Science.gov (United States)

    Breach, Patrick A; Simonovic, Slobodan P

    2018-04-01

    Approximately 20% of wastewaters globally do not receive treatment, whereas wastewater discharges are projected to increase, thereby leading to excessive water quality degradation of surface waters on a global scale. Increased treatment could help alleviate water quality issues by constructing more treatment plants; however, in many areas there exist economic constraints. Energy recovery methods including the utilization of biogas and incineration of biosolids generated during the treatment process may help to alleviate treatment costs. This study explores the potential for investments in energy recovery from wastewater to increase treatment levels and thus improve surface water quality. This was done by examining the relationships between nutrient over-enrichment, wastewater treatment, and energy recovery at a global scale using system dynamics simulation as part of the ANEMI integrated assessment model. The results show that a significant amount of energy can be recovered from wastewater, which helps to alleviate some of the costs of treatment. It was found that wastewater treatment levels could be increased by 34%, helping to offset the higher nutrient loading from a growing population with access to improved sanitation. The production of renewable natural gas from biogas was found to have the potential to prolong the depletion of natural gas resources used to produce electricity and heat. It is recommended that agricultural nutrient discharges be better managed to help reduce nutrient over-enrichment on global scale. To increase the utility of the simulation, a finer spatial scale should be used to consider regional treatment, economic, and water quality characteristics.

  7. Wastewater Treatment Energy Recovery Potential For Adaptation To Global Change: An Integrated Assessment

    Science.gov (United States)

    Breach, Patrick A.; Simonovic, Slobodan P.

    2018-04-01

    Approximately 20% of wastewaters globally do not receive treatment, whereas wastewater discharges are projected to increase, thereby leading to excessive water quality degradation of surface waters on a global scale. Increased treatment could help alleviate water quality issues by constructing more treatment plants; however, in many areas there exist economic constraints. Energy recovery methods including the utilization of biogas and incineration of biosolids generated during the treatment process may help to alleviate treatment costs. This study explores the potential for investments in energy recovery from wastewater to increase treatment levels and thus improve surface water quality. This was done by examining the relationships between nutrient over-enrichment, wastewater treatment, and energy recovery at a global scale using system dynamics simulation as part of the ANEMI integrated assessment model. The results show that a significant amount of energy can be recovered from wastewater, which helps to alleviate some of the costs of treatment. It was found that wastewater treatment levels could be increased by 34%, helping to offset the higher nutrient loading from a growing population with access to improved sanitation. The production of renewable natural gas from biogas was found to have the potential to prolong the depletion of natural gas resources used to produce electricity and heat. It is recommended that agricultural nutrient discharges be better managed to help reduce nutrient over-enrichment on global scale. To increase the utility of the simulation, a finer spatial scale should be used to consider regional treatment, economic, and water quality characteristics.

  8. Attention Deficits in Chronic Methamphetamine Users as a Potential Target for Enhancing Treatment Efficacy

    Directory of Open Access Journals (Sweden)

    Zahra Alam Mehrjerdi

    2012-08-01

    Full Text Available Methamphetamine (MA is a potent, addictive psychostimulant that has dramatic effects on the central nervous system (CNS. The onset of methamphetamine use has been linked to heightened attention, and chronic methamphetamine use has been associated with deficits in different aspects of attention that can significantly persist into abstinence. Attention deficits in chronic methamphetamine users may be associated with severity of methamphetamine use, craving, relapse, and as a result, poor treatment outcomes. This review summarizes evidence that the continuity of attention deficits, especially during abstinence, should be considered as a potential target during methamphetamine use treatment. Implementing attention rehabilitation techniques during treatment may enhance motivation for treatment in chronic methamphetamine users, and may facilitate treatment adherence, craving control and promote relapse prevention. This issue has important clinical implications for enhancing treatment efficacy and as a result, increasing treatment outcomes.

  9. Potential for beneficial application of sulfate reducing bacteria in sulfate containing domestic wastewater treatment.

    Science.gov (United States)

    van den Brand, T P H; Roest, K; Chen, G H; Brdjanovic, D; van Loosdrecht, M C M

    2015-11-01

    The activity of sulfate reducing bacteria (SRB) in domestic wastewater treatment plants (WWTP) is often considered as a problem due to H2S formation and potential related odour and corrosion of materials. However, when controlled well, these bacteria can be effectively used in a positive manner for the treatment of wastewater. The main advantages of using SRB in wastewater treatment are: (1) minimal sludge production, (2) reduction of potential pathogens presence, (3) removal of heavy metals and (4) as pre-treatment of anaerobic digestion. These advantages are accessory to efficient and stable COD removal by SRB. Though only a few studies have been conducted on SRB treatment of domestic wastewater, the many studies performed on industrial wastewater provide information on the potential of SRB in domestic wastewater treatment. A key-parameter analyses literature study comprising pH, organic substrates, sulfate, salt, temperature and oxygen revealed that the conditions are well suited for the application of SRB in domestic wastewater treatment. Since the application of SRB in WWTP has environmental benefits its application is worth considering for wastewater treatment, when sulfate is present in the influent.

  10. Exploring the Patient Experience of Changes in Appetite and Diet with Incretin Analogue Therapy

    OpenAIRE

    Paisey, Rosamund May

    2014-01-01

    Incretin analogue therapies are a valuable recent treatment option for type 2 diabetes (T2D) as they can improve blood glucose control and aid weight loss. The way in which an individual recognises and responds to changes in satiety signals induced by these treatments may explain why individual response is variable. Purposive sampling of individuals with successful outcome of incretin analogue therapy (GLP-1) for T2D gathered a participant cohort 15 people with 37 years (448 months) combined ...

  11. Curcumin and Its Analogue Induce Apoptosis in Leukemia Cells and Have Additive Effects with Bortezomib in Cellular and Xenograft Models

    Directory of Open Access Journals (Sweden)

    L. I. Nagy

    2015-01-01

    Full Text Available Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-κB, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-κB inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3 mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.

  12. Natural analogues, paradigm for manmade repositories for radioactive wastes

    International Nuclear Information System (INIS)

    Pavelescu, M.; Pavelescu, A.

    2004-01-01

    Natural analogues are given by nature. They show the results of natural processes which have lasted thousands or millions of years. They provide an excellent example of what could happen in an underground site, offering in the same time the opportunity to test by observation and measurement, many of the geochemical processes that are expected to influence in a realistic and appropriate way, the predicted reliability of the radioactive waste repository over long periods of geological time. The natural analogue studies attempt to understand the multiprocessing complexity of the natural system, which contrasts with the limitations of the laboratory experiments and bring arguments to overcome the difficult time scale issue. By this the natural analogues are a useful paradigm for manmade repository for radioactive wastes. The paper discusses the implicit link in the public mind between natural analogues and manmade waste repository with an accent of the positive impact on public acceptance. It is also discussed the decisive qualities of the natural analogues concerning providing valid long term data and increasing the confidence of the public for manmade repositories. The debate is conducting in terms of sustainable development, having at base high-level principles in order to protect humans and their environment, both now and in the future, from potential hazards arising from such wastes. Safe radwaste management involves the application of technology and resources in a regulated manner so that the public, workers and the environment are protected in accordance with the accepted national and international standards. There are at least seven high-level principles which are mentioned in the paper. It is presented the general concept of the deep geological repository, very important for an acceptable solution for the management of nuclear waste, what is a prerequisite for a renewal of nuclear power. Further are introduced natural and archaeological (manufactured) analogue

  13. Aryl Trifluoromethyl Iximes: potential new mosquito insecticides

    Science.gov (United States)

    Fluorinated methylketones have been identified as potential mosquitocides, suspected of acting as reaction coordinate analogues that inhibit acetylcholinesterase (AChE) thereby leading to paralysis and eventual death. Previous work has explored trifluoro-, difluoro-, and fluoromethylketone analogues...

  14. Knowledge-based treatment planning and its potential role in the transition between treatment planning systems.

    Science.gov (United States)

    Masi, Kathryn; Archer, Paul; Jackson, William; Sun, Yilun; Schipper, Matthew; Hamstra, Daniel; Matuszak, Martha

    2017-11-22

    Commissioning a new treatment planning system (TPS) involves many time-consuming tasks. We investigated the role that knowledge-based planning (KBP) can play in aiding a clinic's transition to a new TPS. Sixty clinically treated prostate/prostate bed intensity-modulated radiation therapy (IMRT) plans were exported from an in-house TPS and were used to create a KBP model in a newly implemented commercial application. To determine the benefit that KBP may have in a TPS transition, the model was tested on 2 groups of patients. Group 1 consisted of the first 10 prostate/prostate bed patients treated in the commercial TPS after the transition from the in-house TPS. Group 2 consisted of 10 patients planned in the commercial TPS after 8 months of clinical use. The KBP-generated plan was compared with the clinically used plan in terms of plan quality (ability to meet planning objectives and overall dose metrics) and planning efficiency (time required to generate clinically acceptable plans). The KBP-generated plans provided a significantly improved target coverage (p = 0.01) compared with the clinically used plans for Group 1, but yielded plans of comparable target coverage to the clinically used plans for Group 2. For the organs at risk, the KBP-generated plans produced lower doses, on average, for every normal-tissue objective except for the maximum dose to 0.1 cc of rectum. The time needed for the KBP-generated plans ranged from 6 to 15 minutes compared to 30 to 150 and 15 to 60 minutes for manual planning in Groups 1 and 2, respectively. KBP is a promising tool to aid in the transition to a new TPS. Our study indicates that high-quality treatment plans could have been generated in the newly implemented TPS more efficiently compared with not using KBP. Even after 8 months of the clinical use, KBP still showed an increase in plan quality and planning efficiency compared with manual planning. Copyright © 2017 American Association of Medical Dosimetrists. Published

  15. The Valles natural analogue project

    International Nuclear Information System (INIS)

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and 39 Ar/ 4O isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks

  16. The potentiation of the effect of radiation treatment by intratumoral delivery of cisplatin

    International Nuclear Information System (INIS)

    Yapp, Donald T.T.; Lloyd, David K.; Zhu, Julian; Lehnert, Shirley M.

    1998-01-01

    Purpose: To compare potentiation of the effects of acute or fractionated radiation by cisplatin when the drug was delivered intratumorally by implanted biodegradable polymer, by intraperitoneal injection, or by intraperitoneal osmotic pump. Methods and Materials: Radiation was delivered to a mouse tumor (RIF-1) either in a single dose or in a fractionated regime in conjunction with cisplatin delivered either as a bolus injection, with an osmotic pump, or with a biodegradable polymer rod containing cisplatin. The osmotic pump was implanted in the intraperitoneal cavity of the mouse while the polymer implants were placed directly in the tumor. As the polymer degrades, the drug is released at the treatment site leading to high local concentrations. The osmotic pump, in contrast, leads to prolonged systemic exposure to the drug at low concentrations. Tumor growth delay (TGD) was used as an endpoint in these experiments. Results: The most effective treatment protocol, in terms of potentiating the effects of radiation was cisplatin delivered by polymer implanted 2 days before an acute dose of radiation (growth modification factor [DMF] = 2.2). Comparison of single and multifraction regimes where polymer implant was on the same day as the commencement of treatment showed greater potentiation of the effect of fractionated than of acute radiation treatment with the DMF for fractionated treatment remaining relatively constant (1.5-1.9) for 5, 8, and 12 fraction treatments. Cisplatin delivered via the osmotic pump did not deliver a high enough dose of cisplatin to produce therapeutic effect in this mouse tumor model and had little impact on response to treatment. Conclusions: Our results indicated that cisplatin delivered intratumorally by biodegradable polymer implant was effective in potentiating the effect of both acute and fractionated radiation. For the fractionated treatments the effect was maintained with increasing fraction numbers and treatment time

  17. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  18. Valproate in the treatment of epilepsy in girls and women of childbearing potential.

    Science.gov (United States)

    Tomson, Torbjörn; Marson, Anthony; Boon, Paul; Canevini, Maria Paola; Covanis, Athanasios; Gaily, Eija; Kälviäinen, Reetta; Trinka, Eugen

    2015-07-01

    This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA-ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk-benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first-line treatment for focal epilepsy. (5) Valproate may be offered as a first-line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic-clonic seizures. (6) Valproate may be offered as a first-line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls

  19. α-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice.

    Directory of Open Access Journals (Sweden)

    Petteri Rinne

    Full Text Available Melanocyte-stimulating hormones, α-, β- and γ-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that α-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of α-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable α-MSH analogue [Nle(4, D-Phe(7]-α-MSH (NDP-α-MSH and investigated whether it has protective effects in deoxycorticosterone acetate (DOCA-salt hypertensive mice. Adult male C57Bl/6N mice were subjected to DOCA-salt treatment and randomized to receive intraperitoneal injections of either saline as vehicle or NDP-α-MSH (0.3 mg/kg/day for 14 days starting 7 days after the DOCA-salt treatment. Systemic hemodynamics, serum and urine electrolytes, and oxidative stress markers were assessed in control sham-operated and DOCA-salt mice. NDP-α-MSH elicited marked diuretic and natriuretic responses that were reversible with the MC3/4 receptor antagonist SHU9119. Chronic NDP-α-MSH treatment attenuated blood pressure elevation in DOCA-salt mice without affecting the blood pressure of normotensive control animals. Owing to the enhanced sodium excretion, NDP-α-MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt treatment mildly increased oxidative stress at the tissue level, but NDP-α-MSH had no significant effects on the oxidative stress markers. In conclusion, treatment with NDP-α-MSH increases urinary sodium excretion and protects against DOCA-salt-induced hypertension. These findings point to the potential future use of α-MSH analogues in the treatment of hypertension.

  20. Space Analogue Environments: Are the Populations Comparable?

    Science.gov (United States)

    Sandal, G. M.

    were assessed. Most of the polar expeditionners had the combination of high scores on positive expressivity and high achievement motivation- a profile which has sometimes been characterized as "the right stuff" for coping in confined and isolated settings. Conclusion: The findings from this study suggest that populations in various space-analogue environments differ in personality traits which might impact on the comparability of psychological findings obtained in different setting. Gender differences in personality also represent a potential source of variance that need to be addressed when generalizing results across space analogue environments.

  1. Analogues of morphanthridine and the tear gas dibenz[b,f][1,4]oxazepine (CR) as extremely potent activators of the human transient receptor potential ankyrin 1 (TRPA1) channel.

    Science.gov (United States)

    Gijsen, Harrie J M; Berthelot, Didier; Zaja, Mirko; Brône, Bert; Geuens, Ivo; Mercken, Marc

    2010-10-14

    The TRPA1 channel can be considered as a key biological sensor to irritant chemicals. In this paper, the discovery of 11H-dibenz[b,e]azepines (morphanthridines) and dibenz[b,f][1,4]oxazepines is described as extremely potent agonists of the TRPA1 receptor. This has led to the discovery that most of the known tear gases are potent TRPA1 activators. The synthesis and biological activity of a number of substituted morphanthridines and dibenz[b,f][1,4]oxazepines have given insight into the SAR around this class of TRPA1 agonists, with EC(50) values ranging from 1 μM to 0.1 nM. Compounds 6 and 32 can be considered as the most potent TRPA1 agonists known to date, with 6 now being used successfully as a screening tool in the discovery of TRPA1 antagonists. The use of ligands such as 6 and 32 as pharmacological tools may contribute to the basic knowledge of the TRPA1 channel and advance the development of TRPA1 antagonists as potential treatment for conditions involving TRPA1 activation, including asthma and pain.

  2. Ozonation and Thermal Pre-Treatment of Municipal Sewage Sludge-Implications for Toxicity and Methane Potential

    DEFF Research Database (Denmark)

    Davidsson, A.; Eriksson, Eva; Fick, J.

    2013-01-01

    The aim of this study was to determine effects on methane potential and overall sludge quality from two different sludge pre-treatment technologies (ozonation high/low dosage and thermal treatment 55/70 degrees C). In general both treatments produced increased methane potential. Thermal treatment...

  3. Brief hierarchical assessment of potential treatment components with children in an outpatient clinic.

    OpenAIRE

    Harding, J; Wacker, D P; Cooper, L J; Millard, T; Jensen-Kovalan, P

    1994-01-01

    Seven patients conducted assessments in an outpatient clinic using a prescribed hierarchy of antecedent and consequence treatment components for their children's problem behavior. Brief assessment of potential treatment components was conducted to identify variables that controlled the children's appropriate behavior. Experimental control via a brief reversal was achieved for 6 of the 7 children, (1 child continued to behave appropriately following initial improvement in behavior). For these ...

  4. Potential of Waste Water Sludge as Environmental-Friendly Manure after UV-Treatment

    OpenAIRE

    Laila Zafar; Asif Javed; Syed Shahid Ali; Zubair Anwar; Jabar Zaman Khan Khattak

    2012-01-01

    Due to exponential population increase in developing world, the wastewater and solid waste generation has tremendously increased and their management has become a serious health and environmental issue. A large amount of sewage sludge generated by sewage treatment plants however, can be re-used after proper segregation and treatment as fertilizer and for energy production. Hence, this study was carried out to find out the potential use of sludge produced at Islamabad Capital Territory (ICT) S...

  5. Spotlight on botulinum toxin and its potential in the treatment of stroke-related spasticity

    Science.gov (United States)

    Kaku, Michelle; Simpson, David M

    2016-01-01

    Poststroke spasticity affects up to one-half of stroke patients and has debilitating effects, contributing to diminished activities of daily living, quality of life, pain, and functional impairments. Botulinum toxin (BoNT) is proven to be safe and effective in the treatment of focal poststroke spasticity. The aim of this review is to highlight BoNT and its potential in the treatment of upper and lower limb poststroke spasticity. We review evidence for the efficacy of BoNT type A and B formulations and address considerations of optimal injection technique, patient and caregiver satisfaction, and potential adverse effects of BoNT. PMID:27022247

  6. Identifying potential moderators for response to treatment in low back pain: A systematic review.

    Science.gov (United States)

    Gurung, Tara; Ellard, David R; Mistry, Dipesh; Patel, Shilpa; Underwood, Martin

    2015-09-01

    Identifying which patients with non-specific low back pain are likely to gain the greatest benefit from different treatments is an important research priority. Few studies are large enough to produce data on sub-group effects from different treatments. Data from existing large studies may help identify potential moderators to use in future individual patient data meta-analyses. To systematically review papers of therapist delivered interventions for low back pain to identify potential moderators to inform an individual patient data meta-analysis. We searched MEDLINE, EMBASE, Web of Science and Citation Index and Cochrane Register of Controlled Trials (CENTRALhttp://www.cochrane.org/editorial-and-publishing-policy-resource/cochrane-central-register-controlled-trials-central) for relevant papers. We screened for randomised controlled trials with ≥500 or more participants, and cohort studies of ≥1000 or more participants. We examined all publications related to these studies for any reported moderator analyses. Two reviewers independently did risk of bias assessment of main results and quality assessment of any moderator analyses. We included four randomised trials (n=7208). Potential moderators with strong evidence (pback pain status, narcotic medication use, treatment expectations and education. Potential moderators with weaker evidence (0.05pain/disability and quality of life. There are insufficient robust data on moderators to be useful in clinical practice. This review has identified some important potential moderators of treatment effect worthy of testing in future confirmatory analyses. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Effect of pre-treatments on methane production potential of energy crops and crop residues

    Energy Technology Data Exchange (ETDEWEB)

    Lehtomaki, A.; Ronkainen; Rintala, J.A. [Jyvaskla Univ. (Finland). Dept. of Biological and Environmental Sciences; Viinikainen, T.A. [Jyvaskla Univ. (Finland). Dept. of Chemistry

    2004-07-01

    Energy crops, that is, crops grown specifically for energy purposes are an alternative to food production in areas with sufficient agricultural land. Crop residues are also a potential source of energy. The anaerobic digestion of solid materials is limited by hydrolysis of complex polymeric substances such as lignocellulose. The methane producing potential of ligno cellulosic material is to pretreat the substrate in order to break up the polymer chains to more easily accessible soluble compounds. In this study, three different substrates were used: sugar beet tops, grass hay, and straw of oats. Biological pretreatments were the following: enzyme treatment, composting, white-rot fungi treatment. Also, pretreatment in water was tried. Chemical pretreatments included peracetic acid treatment, and treatment with two different alkalis. Alkaline pretreatments of hay and sugar beet tops have the potential to improve the methane yield. For instance, the yield of grass hay was increased 15 per cent by one particular alkaline treatment. Straw did not respond to any of the treatments tried. 18 refs., 1 tab., 2 figs.

  8. Genome-wide modulation of gene transcription in ovarian carcinoma cells by a new mithramycin analogue.

    Directory of Open Access Journals (Sweden)

    Carolina Vizcaíno

    Full Text Available Ovarian cancer has a poor prognosis due to intrinsic or acquired resistance to some cytotoxic drugs, raising the interest in new DNA-binding agents such as mithramycin analogues as potential chemotherapeutic agents in gynecological cancer. Using a genome-wide approach, we have analyzed gene expression in A2780 human ovarian carcinoma cells treated with the novel mithramycin analogue DIG-MSK (demycarosyl-3D-β-D-digitoxosyl-mithramycin SK that binds to C+G-rich DNA sequences. Nanomolar concentrations of DIG-MSK abrogated the expression of genes involved in a variety of cell processes including transcription regulation and tumor development, which resulted in cell death. Some of those genes have been associated with cell proliferation and poor prognosis in ovarian cancer. Sp1 transcription factor regulated most of the genes that were down-regulated by the drug, as well as the up-regulation of other genes mainly involved in response to cell stress. The effect of DIG-MSK in the control of gene expression by other transcription factors was also explored. Some of them, such as CREB, E2F and EGR1, also recognize C/G-rich regions in gene promoters, which encompass potential DIG-MSK binding sites. DIG-MSK affected several biological processes and molecular functions related to transcription and its cellular regulation in A2780 cells, including transcription factor activity. This new compound might be a promising drug for the treatment of ovarian cancer.

  9. Ethanol production potential from fermented rice noodle wastewater treatment using entrapped yeast cell sequencing batch reactor

    Science.gov (United States)

    Siripattanakul-Ratpukdi, Sumana

    2012-03-01

    Fermented rice noodle production generates a large volume of starch-based wastewater. This study investigated the treatment of the fermented rice noodle wastewater using entrapped cell sequencing batch reactor (ECSBR) compared to traditional sequencing batch reactor (SBR). The yeast cells were applied because of their potential to convert reducing sugar in the wastewater to ethanol. In present study, preliminary treatment by acid hydrolysis was performed. A yeast culture, Saccharomyces cerevisiae, with calcium alginate cell entrapment was used. Optimum yeast cell loading in batch experiment and fermented rice noodle treatment performances using ECSBR and SBR systems were examined. In the first part, it was found that the cell loadings (0.6-2.7 × 108 cells/mL) did not play an important role in this study. Treatment reactions followed the second-order kinetics with the treatment efficiencies of 92-95%. In the second part, the result showed that ECSBR performed better than SBR in both treatment efficiency and system stability perspectives. ECSBR maintained glucose removal of 82.5 ± 10% for 5-cycle treatment while glucose removal by SBR declined from 96 to 40% within the 5-cycle treatment. Scanning electron microscopic images supported the treatment results. A number of yeast cells entrapped and attached onto the matrix grew in the entrapment matrix.

  10. Treatment of experimental allergic encephalomyelitis (EAE) induced by guinea pig myelin basic protein epitope 72-85 with a human MBP(87-99) analogue and effects of cyclic peptides.

    Science.gov (United States)

    Tselios, T; Daliani, I; Probert, L; Deraos, S; Matsoukas, E; Roy, S; Pires, J; Moore, G; Matsoukas, J

    2000-08-01

    Experimental autoimmune encephalomyelitis (EAE) is an inflammatory and demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). In the present report, a linear analogue and a series of cyclic semi-mimetic peptides were designed and synthesized based on the human myelin basic protein (MBP(87-99)) epitope (Val87-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro90) and on Copolymer I (a mixture of random polymers of Ala, Gln, Lys and Tyr used to treat MS). These analogues were designed looking for suppressors of EAE induced by guinea pig MBP(72-85) epitope (Gln-Lys-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-Pro-Val) in Lewis rats. The linear analogue [Arg91,Ala96]MBP(87-99), in which Arg substitutes Lys91 and Ala substitutes Pro96, was found to be a strong inhibitor which when administered to Lewis rats together with the encephalitogenic agonist MBP(72-85) completely prevented the induction of EAE. In contrast, three N- and C-termini amide-linked cyclic semi-mimetic peptides, [cyclo-Phe-Arg-Asn-Ile-Val-Thr-Ala-Acp (1), cyclo-Phe-Ala-Arg-Gln-Acp (2), cyclo-Tyr-Ala-Lys-Gln-Acp (3)] as well as a Lys side chain and C-terminous cyclic semi mimetic peptide cyclo(Lys, Acp)-Phe-Lys-Asn-Ile-Val-Thr-Ala-Acp (4) which contain segments of MBP(87-99) or are constituted from immunophoric residues of copolymer 1, were ineffective in inducing or inhibiting EAE in Lewis rats. However co-injection of cyclic analogues with MBP(72-85) delayed the onset of EAE indicating a modulatory effect on the EAE activity of MBP(72-85). These findings suggest that molecule length, size of cyclic moiety and backbone conformation are important elements for immunogenic activity. Moreover blockade of MBP(72-85) induced EAE by the unrelated peptide [Arg91,Ala56]MBP(87-99) could indicate that the mechanism of inhibition is not due to binding competition but rather due to the delivery of a negative signal by the antagonist which overcomes the agonist response possibly

  11. Drug evaluation: The MTP inhibitor JTT-130 as a potential treatment for hyperlipidemia.

    Science.gov (United States)

    Burnett, John R

    2006-07-01

    Japan Tobacco Inc is developing JTT-130, an orally active microsomal triglyceride transfer protein inhibitor, for the potential treatment of hyperlipidemia. By August 2005, the compound was undergoing a phase II clinical trial in Japan, as well as a phase I trial in Europe.

  12. Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Torp, Thomas Lee; Lundberg, Kristian

    Title of abstract: Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy Design of study: Three months prospective, interventional clinical study. Purpose: The retinal vascular tree can be measured non-invasively and summarized...

  13. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

    Directory of Open Access Journals (Sweden)

    Sathish Sundar Dhilip Kumar

    2018-04-01

    Full Text Available Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  14. Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Fabliha Ahmed Chowdhury

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ, the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

  15. Microbiota abnormalities and the therapeutic potential of probiotics in the treatment of mood disorders.

    Science.gov (United States)

    Rios, Adiel C; Maurya, Pawan Kumar; Pedrini, Mariana; Zeni-Graiff, Maiara; Asevedo, Elson; Mansur, Rodrigo B; Wieck, Andrea; Grassi-Oliveira, Rodrigo; McIntyre, Roger S; Hayashi, Mirian A F; Brietzke, Elisa

    2017-10-26

    Major depressive disorder (MDD) and bipolar disorder (BD) are among the leading causes of burden and disability worldwide. Despite intensified research efforts to improve the treatment options and remission rates in mood disorders, no disease modifying treatment exists for these disorders. Accumulating evidence implicates the involvement of the gut microbiota in processes relevant to etiopathology of central nervous system-based disorders. The objective of this article was to critically evaluate the evidence supporting the link between gastrointestinal microbiota and mood disorders and to discuss the potential benefits of using probiotics in the treatment of MDD and BD. The concept of psychobiotics, which is bacterial-based interventions with mental health benefit, is emerging in the field. On the other hand, while probiotics might potentially represent a significant advance, specific roles of microbiota in the pathophysiology of mood disorders still need further investigation along with intervention studies.

  16. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  17. On the Use of the Analogue Transformation Acoustics in Aeroacoustics

    Directory of Open Access Journals (Sweden)

    Umberto Iemma

    2017-01-01

    Full Text Available The objective of the paper is the assessment of the Analogue Transformation Acoustics (ATA in the design of acoustic metamaterial for aeronautical applications. The work focuses on the consistency of the background flow resulting from the application of the ATA with the equations governing the potential aerodynamics. Indeed, in case of acoustic perturbations propagating within moving media, the convective terms in the governing equations are responsible for the failure of formal invariance under the action of conformal mappings. The ATA approach overcomes this limitation, introducing the possibility of handling the convective form of the wave equation in a straightforward and elegant way. It is based on the concept of analogue space-time and fully relies on the analytical tools of Lorentzian differential geometry. The present paper analyses the relationship between the analogue velocity field with a realistic potential flow. The method is validated through numerical simulations using two widely assessed acoustic cloaking problems. The preliminary results obtained show that the use of numerical, quasi-conformal mappings can lead to transformed streamlines negligibly deviating from those of the potential velocity field satisfying the fluid-dynamic conservation laws, but with incompatible intensity of the local velocity.

  18. Neuroimaging as a potential biomarker to optimize psychiatric research and treatment.

    Science.gov (United States)

    Walton, Esther; Turner, Jessica A; Ehrlich, Stefan

    2013-10-01

    Complex, polygenic phenotypes in psychiatry hamper our understanding of the underlying molecular pathways and mechanisms of many diseases. The unknown aetiology, together with symptoms which often show a large variability both across individuals and over time and also tend to respond comparatively slowly to medication, can be a problem for patient treatment and drug development. We argue that neuroimaging has the potential to improve psychiatric treatment in two ways. First, by reducing phenotypic complexity, neuroimaging intermediate phenotypes can help to identify disease-related genes and can shed light into the biological mechanisms of known risk genes. Second, quantitative neuroimaging markers - reflecting the spectrum of impairment on a brain-based level - can be used as a more sensitive, reliable and immediate treatment response biomarker. In the end, enhancing both our understanding of the pathophysiology of psychiatric disorders and the prediction of treatment success could eventually optimise current therapy plans.

  19. Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues.

    Directory of Open Access Journals (Sweden)

    Geoffrey D Coxon

    Full Text Available Defining the pharmacological target(s of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61 or HadC (at Val85, Lys157 or Thr123, which are components of the β-hydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors.

  20. Glucose as substrate and signal in priming: Results from experiments with non-metabolizable glucose analogues

    Science.gov (United States)

    Mason-Jones, Kyle; Kuzyakov, Yakov

    2016-04-01

    Priming of soil organic matter remains the subject of intense research, but a mechanistic explanation of the phenomenon remains to be demonstrated. This is largely due to the multiple effects of easily available carbon on the soil microbial community, and the challenge of separating these influences from one another. Several glucose analogues can be taken up by microbial glucose transporters and have similar regulatory effects on metabolism. These substances are, however, not easily catabolized by the common glycolytic pathway, limiting their energy value. Therefore, they can be used to distinguish between the action of glucose as a metabolic signal, and its influence as an energy source. We incubated an agricultural Haplic Luvisol under controlled conditions for 24 days after addition of: 1) glucose, 2) 3-O-methyl-glucose, 3) α-methylglucoside or 4) 2-deoxyglucose, at three concentration levels, along with a control treatment of water addition. CO2 efflux from soil was monitored by trapping evolved CO2 in NaOH and back-titration with HCl. On the first day after amendment, CO2 efflux from soil increased strongly for glucose and much less for the analogues, relative to the control. Only glucose caused a peak in efflux within the first two days. Peak mineralization of 2-deoxyglucose and α-methylglucoside was delayed until the third day, while CO2 from 3-O-methyl-glucose increased gradually, with a peak delayed by approximately a week. For glucose, the immediate increase in respiration was strongly dependent on the amount of glucose added, but this was not the case for the analogues, indicating that the catabolic potential for these substances was saturated. This is consistent with only a small part of the microbial community being capable of utilizing these carbon sources. In a subsequent experiment, 14C-labelled glucose or 14C-labelled 3-O-methyl-glucose were added to the same soil, enabling quantification of the priming effect. For 3-O-methyl-glucose, priming was

  1. Fluocinolone acetonide and its potential in the treatment of chronic diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Haritoglou C

    2013-03-01

    Full Text Available Christos Haritoglou, Aljoscha S Neubauer, Marcus KerntDepartment of Ophthalmology, Ludwig-Maximilians-University, Munich, GermanyAbstract: Diabetic macular edema (DME is a potentially sight-threatening disease that predominantly affects patients with type 2 diabetes. The pathogenesis is complex, with many contributing factors involved. In addition to overexpression of vascular endothelial growth factor in the diabetic eye, there is an inflammatory pathway that contributes to the breakdown of the blood-retina barrier and nonperfusion. In addition to vascular endothelial growth factor inhibitors, clinical and experimental investigations underline the great potential of steroids in the treatment of DME. Fluocinolone acetonide is currently the only corticosteroid approved for the treatment of DME in Europe. It is manufactured as an intravitreal insert, releasing fluocinolone acetonide at a rate of 0.2 µg per day. Phase III clinical studies have demonstrated that the beneficial effect of the fluocinolone acetonide insert lasts up to 3 years. Improvement in visual acuity was especially remarkable in patients with a prolonged duration of DME of at least 3 years at the initiation of therapy. Cataract formation occurs in nearly all phakic eyes treated, and needs to be considered when the indication for treatment is made. Given the efficacy versus potential complications of the insert, fluocinolone acetonide represents a promising second-line treatment option in patients with DME. Fluocinolone appears to be especially beneficial for patients whose options for visual recovery have seemed limited up until now.Keywords: diabetic macular edema, fluocinolone acetonide

  2. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-01-01

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  3. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  4. Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy.

    Science.gov (United States)

    Ramasamy, Thamil Selvee; Ayob, Ain Zubaidah; Myint, Hsu Hsu Lynn; Thiagarajah, Sharmanee; Amini, Farahnaz

    2015-01-01

    Colorectal cancer is one of the commonest cancers in the world and it is also a common cause of cancer-related death worldwide. Despite advanced treatment strategies, the disease is rarely cured completely due to recurrence. Evidence shows that this is due to a small population of cells, called cancer stem cells (CSCs), in the tumour mass that have the self-renewal and differentiation potential to give rise to a new tumour population. Many pre-clinical and clinical studies have used curcumin and its analogues as anti-cancer agents in various types of cancer, including colorectal cancer. Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth. In this review, we highlight the efficacy of curcumin and its analogues in targeting colorectal CSC and also the underlying molecular mechanism involved. Curcumin, in the presence or absence of other anti-cancer agents, has been shown to reduce the size of tumour mass and growth in both in vivo and in vitro studies by affecting many intracellular events that are associated with cancer progression and CSC formation. An insight into the molecular mechanism has unraveled the mode of action via which curcumin could affect the key regulators in CSC, importantly; (1) the signaling pathways, including Wnt/β-catenin, Sonic Hedgehog, Notch and PI3K/Akt/mTOR, (2) microRNA and (3) the epithelial-mesenchymal transition at multiple levels. Therefore, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy, therefore, combination therapy using anti-cancer agent with curcumin could be much more effective than treatment using a single cancer agent. This potential treatment modality can be further developed by employing an effective delivery system using a nanotechnology based approach to treat colorectal cancer.

  5. Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P.; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-01

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

  6. Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-02

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. POTENTIAL USE OF MICROBIAL ELECTROLYSIS CELLS (MECs IN DOMESTIC WASTEWATER TREATMENT PLANTS FOR ENERGY RECOVERY

    Directory of Open Access Journals (Sweden)

    Adrian eEscapa

    2014-06-01

    Full Text Available Globally, large amounts of electrical energy are spent every year for domestic wastewater (dWW treatment. In the future, energy prices are expected to rise as the demand for energy resources increases and fossil fuel reserves become depleted. By using appropriate technologies, the potential chemical energy contained in the organic compounds present in dWWs might help to improve the energy and economic balance of dWW treatment plants. Bioelectrochemical Systems (BESs in general and microbial electrolysis cells (MECs in particular represent an emerging technology capable of harvesting part of this energy. This study offers an overview of the potential of using MEC technology in dWW treatment plants (dWWTPs to reduce the energy bill. It begins with a brief account of the basics of BESs, followed by an examination of how MECs can be integrated in dWW treatment plants (dWWTPs, identifying scaling-up bottlenecks and estimating potential energy savings. A simplified analysis showed that the use of MEC technology may help to reduce up to ~20% the energy consumption in a conventional dWWTP. The study concludes with a discussion of the future perspectives of MEC technology for dWW treatment. The growing rates of municipal water and wastewater treatment markets in Europe offer excellent business prospects and it is expected that the first generation of MECs could be ready within 1-4 years. However, before MEC technology may achieve practical implementation in dWWTPs, it needs not only to overcome important techno-economic challenges, but also to compete with other energy-producing technologies.

  8. Conducting polypyrrole films as a potential tool for electrochemical treatment of azo dyes in textile wastewaters

    Energy Technology Data Exchange (ETDEWEB)

    Haque, Md. Mominul [Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109 (Australia); Smith, Warren T. [Samadha Pacifica Pty Ltd, Woonona, NSW 2517 (Australia); Wong, Danny K.Y., E-mail: Danny.Wong@mq.edu.au [Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109 (Australia)

    2015-02-11

    Highlights: • Anion exchange property of polypyrrole films exploited in developing a treatment method for Acid Red 1. • An environmentally friendly treatment method for Acid Red 1 without generating any toxic by-products. • Acid Red 1 is anodically entrapped and cathodically liberated at polypyrrole films. • Analytical characteristics of Acid Red 1-entrapped polypyrrole films. - Abstract: In this paper, we demonstrate conducting polypyrrole films as a potential green technology for electrochemical treatment of azo dyes in wastewaters using Acid Red 1 as a model analyte. These films were synthesised by anodically polymerising pyrrole in the presence of Acid Red 1 as a supporting electrolyte. In this way, the anionic Acid Red 1 is electrostatically attracted to the cationic polypyrrole backbone formed to maintain electroneutrality, and is thus entrapped in the film. These Acid Red 1-entrapped polypyrrole films were characterised by electrochemical, microscopic and spectroscopic techniques. Based on a two-level factorial design, the solution pH, Acid Red 1 concentration and polymerisation duration were identified as significant parameters affecting the entrapment efficiency. The entrapment process will potentially aid in decolourising Acid Red 1-containing wastewaters. Similarly, in a cathodic process, electrons are supplied to neutralise the polypyrrole backbone, liberating Acid Red 1 into a solution. In this work, following an entrapment duration of 480 min in 2000 mg L{sup −1} Acid Red 1, we estimated 21% of the dye was liberated after a reduction period of 240 min. This allows the recovery of Acid Red 1 for recycling purposes. A distinctive advantage of this electrochemical Acid Red 1 treatment, compared to many other techniques, is that no known toxic by-products are generated in the treatment. Therefore, conducting polypyrrole films can potentially be applied as an environmentally friendly treatment method for textile effluents.

  9. CH4 emissions and reduction potential in wastewater treatment in China

    Directory of Open Access Journals (Sweden)

    Zhan-Yun Ma

    2015-09-01

    Full Text Available The treatment of domestic and industrial wastewater is one of the major sources of CH4 in the Chinese waste sector. On the basis of statistical data and country-specific emission factors, using IPCC methodology, the characteristics of CH4 emissions from wastewater treatment in China were analyzed. The driving factors of CH4 emissions were studied, and the emission trend and reduction potential were predicted and analyzed according to the current situation. Results show that in 2010, CH4 emissions from the treatment of domestic and industrial wastewater were 0.6110 Mt and 1.6237 Mt, respectively. Eight major industries account for more than 92% of emissions, and CH4 emissions gradually increased from 2005 to 2010. From the controlling management scenario, we predict that in 2020, CH4 emissions from the treatment of domestic and industrial wastewater will be 1.0136 Mt and 2.3393 Mt, respectively, and the reduction potential will be 0.0763 Mt and 0.2599 Mt, respectively. From 2010 to 2020, CH4 emissions from the treatment of domestic and industrial wastewater will increase by 66% and 44%, respectively.

  10. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Keller-von Amsberg G

    2013-03-01

    Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML. Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance

  11. Is there potential for repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment of OCD?

    Science.gov (United States)

    Zaman, Rashid; Robbins, Trevor W

    2017-09-01

    Obsessive-Compulsive Disorder (OCD) is a common and highly debilitating psychiatric disorder. Amongst OCD sufferers are a significant number (40-60%) of so-called non-responders who do not fully respond to commonly available treatments, which include medications (Selective Serotonin Reuptake Inhibitors-SSRIs) and cognitive behavior therapy (CBT). Modern 'neuromodulatory' techniques such as Deep Brain Stimulation (DBS), repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) potentially offer alternative forms of treatment for OCD patients who either do not respond to, or are unable or unwilling to take SSRIs and undergo CBT. Although shown to be effective in treatment resistant OCD, DBS requires invasive neurosurgical procedures with associated risks. On the other hand, rTMS and tDCS are non-invasive forms of treatment, which are largely risk free, but the evidence of their efficacy so far is somewhat limited, with only small number of published studies. In this brief survey we will address the potential of rTMS as a therapeutic tool for OCD and review the published literature on the cortical targets for rTMS used so far. We will also discuss some of the newer variants of rTMS techniques only a few of which have been employed so far, and speculate whether there might be a place for rTMS as a standard treatment in OCD, along side CBT, SSRIs and DBS.

  12. An analysis of the market potential of water hyacinth-based systems for municipal wastewater treatment

    Science.gov (United States)

    Robinson, A. C.; Gorman, H. J.; Hillman, M.; Lawhon, W. T.; Maase, D. L.; Mcclure, T. A.

    1976-01-01

    The potential U.S. market for tertiary municipal wastewater treatment facilities which make use of water hyacinths was investigated. A baseline design was developed which approximates the "typical" or "average" situation under which hyacinth-based systems can be used. The total market size for tertiary treatment was then estimated for those geographical regions in which hyacinths appear to be applicable. Market penetration of the baseline hyacinth system when competing with conventional chemical and physical processing systems was approximated, based primarily on cost differences. A limited analysis was made of the sensitivity of market penetration to individual changes in these assumptions.

  13. Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

    Science.gov (United States)

    Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

    1993-04-01

    Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

  14. Long-acting lipidated analogue of human pancreatic polypeptide is slowly released into circulation

    DEFF Research Database (Denmark)

    Bellmann-Sickert, Kathrin; Elling, Christian E; Madsen, Andreas N

    2011-01-01

    The main disadvantages of peptide pharmaceuticals are their rapid degradation and excretion, their low hydrophilicity, and low shelf lifes. These bottlenecks can be circumvented by acylation with fatty acids (lipidation) or polyethylene glycol (PEGylation). Here, we describe the modification....... Lipidation resulted in prolonged action of the hPP analogue in respect of reducing food intake in mice after subcutaneous administration. Therefore, the lipidated hPP analogue could constitute a potential new therapeutic agent against obesity....

  15. Synthesis of pyrimidine containing nucleoside β-(R/S)-hydroxyphosphonate analogues

    OpenAIRE

    Meurillon, Maïa; Chaloin, Laurent; Peyrottes, Suzanne; Périgaud, Christian

    2011-01-01

    A concise route to nucleoside β-hydroxyphosphonate analogues is described. The use of a nucleoside β-ketophosphonate as the key intermediate allowed both the (R) and (S) isomers of β-hydroxyphosphonate analogues in the pyrimidine series to be accessed. Such derivatives may be considered as stable mimics of 5′-monophosphate nucleosides and, therefore, could be the starting point for the development of potential therapeutic agents.

  16. Labelling and evaluation of new stabilised neurotensin (8-13) analogues for SPET

    International Nuclear Information System (INIS)

    Chavatte, K.; Terriere, D.; Jeannin, L.

    1998-01-01

    Neurotensin (8-13) analogues were biologically stabilised by replacement of the peptide bond between amino acids 8 and 9 by the reduced ψ(CH 2 -NH) isostere. DTPA analogues for In-111 labelling and 2-bromo-phenyl-acetyl analogues for radioiodination, showed receptor affinities in the low nanomolar range in combination with a biological half live in human plasma up to 275 minutes. Biodistribution studies in male Wistar rats of metabolically stabilised and non-stabilised 111 In-DTPA-NT(8-13) analogues showed a major clearance from the blood through the kidneys. 125 I-labelled Neurotensin (8-13) analogues showed accumulation up to 2.2% of the injected dose per g tissue in the liver which might be an important disadvantage when diagnosis of tumours in the gut is aimed. It is strongly suggested that stabilised neurotensin (8-13) analogues whether labelled with In-111, I-123 and the near future with Tc-99m, may act as new potential peptidergic radiopharmaceuticals for SPET diagnosis of different NT-receptor positive tumours like non-endocrine pancreas carcinoma, small cell lung carcinoma or colon adeno carcinoma. It is enticing to speculate that metabolically stabilised Neurotensin (8-13) analogues labelled with an appropriate isotope might be useful in therapy of different human cancers. (author)

  17. Effects of the hydrogen potential and fungicide treatment on Pitaya seed germination

    OpenAIRE

    Ortiz, Thiago Alberto; Moritz, Aline; Oliveira, Mariana Alves de; Takahashi, Lúcia Sadayo Assari

    2015-01-01

    The objective of the present study was to evaluate pitaya seed germination under different hydrogen potentials, with or without fungicide treatment. A completely randomized design was employed under a 3 x 13 x 2 factorial scheme, corresponding to three pitaya species (white pitaya, pitaya hybrid I, pitaya hybrid II), thirteen hydrogen potentials (3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, and 9.0) and two fungicide conditions (presence and absence), with four replications. Th...

  18. Condensed matter analogues of cosmology

    Science.gov (United States)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the

  19. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    Malik Chalal

    2014-06-01

    Full Text Available Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew. Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold. The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups and antimicrobial activity.

  20. Synthesis and preliminary cytotoxicity study of a cephalosporin-CC-1065 analogue prodrug

    Directory of Open Access Journals (Sweden)

    Wang Hong

    2001-11-01

    Full Text Available Abstract Background Antibody-directed enzyme prodrug therapy (ADEPT is a promising new approach to deliver anticancer drugs selectively to tumor cells. In this approach, an enzyme is conjugated to a tumor-specific antibody. The antibody selectively localizes the enzyme to the tumor cell surface. Subsequent administration of a prodrug substrate of the enzyme leads to the enzyme-catalyzed release of the free drug at the tumor site. The free drug will destroy the tumor cells selectively, thus, reducing side effects. Results A CC-1065 analogue was conjugated to a cephalosporin affording prodrug 2. The prodrug and its corresponding free drug, 1, have IC50 values of 0.9 and 0.09 nM, respectively, against U937 leukemia cells in vitro. Conclusions For the first time, a prodrug comprised of a cephalosporin and a CC-1065 analogue has been synthesized. The preliminary in vitro studies show that the prodrug was 10-fold less toxic than the free drug. Prodrug 2 has the potential to be useful in cancer treatment using the ADEPT approach.

  1. Parallel synthesis and biological evaluation of 837 analogues of procaspase-activating compound 1 (PAC-1).

    Science.gov (United States)

    Hsu, Danny C; Roth, Howard S; West, Diana C; Botham, Rachel C; Novotny, Chris J; Schmid, Steven C; Hergenrother, Paul J

    2012-01-09

    Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3.

  2. Amyloid binding properties of curcumin analogues in Alzheimer's disease postmortem brain tissue.

    Science.gov (United States)

    Veldman, Emma R; Jia, Zhisheng; Halldin, Christer; Svedberg, Marie M

    2016-09-06

    The presence of β-amyloid (Aβ) containing plaques in the brain is a hallmark of Alzheimer's disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Early diagnosis is of great importance for optimal treatment and for monitoring disease progression in the brain. Highly specific and sensitive biomarkers are thus greatly needed to assess therapeutic efficacy, not only clinically, but also in terms of clearance of histopathological lesions and decelerated neurodegeneration. The objective of the present study was to give more insight into the binding of curcumin analogues, curcuminoids, to Aβ containing plaques in postmortem tissue from AD patients. In vitro autoradiography was utilized to explore affinity and displacement of the curcuminoids; curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) and dimethoxycurcumin (DIMC). We found that BDMC had the highest affinity for Aβ containing plaques in cortical AD brain tissue in comparison to other curcuminoids. Subsequently, [(3)H]BDMC showed significantly higher specific binding in cortical AD brain tissue compared to control subjects. These findings suggest that curcumin analogues, especially BDMC, may serve as a potential radioligands for Aβ plaque neuroimaging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Voriconazole as a first-line treatment against potentially pathogenic Acanthamoeba strains from Peru.

    Science.gov (United States)

    Cabello-Vílchez, Alfonso Martín; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Reyes-Batlle, María; Sifaoui, Ines; Valladares, Basilio; Piñero, José E; Lorenzo-Morales, Jacob

    2014-02-01

    Pathogenic strains of Acanthamoeba genus are the causative agents of fatal granulomatous amoebic encephalitis and a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. In a previous study, Acanthamoeba strains were isolated from nasal swabs collected from healthy individuals in Peru. In the present study, the pathogenic potential of the isolated strains was established based on temperature and osmotolerance assays as well as the secretion rate of extracellular proteases. Based on these experiments, four strains that showed the highest pathogenic potential were selected for sensitivity assays against two molecules (voriconazole and chlorhexidine) which are currently used for the treatment of Acanthamoeba infections. After performing sensitivity and activity assays, it was found that both drugs were active against the tested strains. However, voriconazole showed higher activity against the studied strains compared to chlorhexidine. Therefore, voriconazole should be established as a first-line treatment against Acanthamoeba infections at least in the studied region of Peru.

  4. Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

    Directory of Open Access Journals (Sweden)

    A.G.M. Mostofa

    2017-06-01

    Full Text Available Thymoquinone (TQ, the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological properties of TQ to rationalize its supplementary role in potentiating the efficacy of standard therapeutic modalities namely surgery, radiotherapy, chemotherapy, and immunotherapy. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical levels to delineate its implied utility as a novel complementary adjuvant therapy for cancer treatment.

  5. Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Armaković, Stevan, E-mail: stevan.armakovic@df.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Physics, Trg Dositeja Obradovića 4, 21000, Novi Sad (Serbia); Armaković, Sanja J. [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000, Novi Sad (Serbia); Holodkov, Vladimir [Educons University, Faculty of Sport and Tourism - TIMS, Radnička 30a, 21000, Novi Sad (Serbia); Pelemiš, Svetlana [University of East Sarajevo, Faculty of Technology, Karakaj bb, 75400, Zvornik, Republic of Srpska, Bosnia and Herzegovina (Bosnia and Herzegovina)

    2016-02-15

    We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S{sub 1}−T{sub 1}). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S{sub 1}−T{sub 1}) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S{sub 1}−T{sub 1}), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

  6. Metforminium Decavanadate as a Potential Metallopharmaceutical Drug for the Treatment of Diabetes Mellitus

    OpenAIRE

    Samuel Treviño; Denisse Velázquez-Vázquez; Eduardo Sánchez-Lara; Alfonso Diaz-Fonseca; José Ángel Flores-Hernandez; Aarón Pérez-Benítez; Eduardo Brambila-Colombres; Enrique González-Vergara

    2016-01-01

    New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM) and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca), a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatm...

  7. Potential Use of Microbial Electrolysis Cells in Domestic Wastewater Treatment Plants for Energy Recovery

    International Nuclear Information System (INIS)

    Escapa, Adrián; San-Martín, María Isabel; Morán, Antonio

    2014-01-01

    Globally, large amounts of electrical energy are spent every year for domestic wastewater (dWW) treatment. In the future, energy prices are expected to rise as the demand for energy resources increases and fossil fuel reserves become depleted. By using appropriate technologies, the potential chemical energy contained in the organic compounds present in dWWs might help to improve the energy and economic balance of dWW treatment plants. Bioelectrochemical systems (BESs) in general and microbial electrolysis cells (MECs) in particular represent an emerging technology capable of harvesting part of this energy. This study offers an overview of the potential of using MEC technology in domestic wastewater treatment plants (dWWTPs) to reduce the energy bill. It begins with a brief account of the basics of BESs, followed by an examination of how MECs can be integrated in dWWTPs, identifying scaling-up bottlenecks and estimating potential energy savings. A simplified analysis showed that the use of MEC technology may help to reduce up to ~20% the energy consumption in a conventional dWWTP. The study concludes with a discussion of the future perspectives of MEC technology for dWW treatment. The growing rates of municipal water and wastewater treatment markets in Europe offer excellent business prospects and it is expected that the first generation of MECs could be ready within 1–4 years. However, before MEC technology may achieve practical implementation in dWWTPs, it need not only to overcome important techno-economic challenges, but also to compete with other energy-producing technologies.

  8. Myosin Light Chain Kinase: A Potential Target for Treatment of Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yongjian Xiong

    2017-05-01

    Full Text Available Myosin light chain kinase (MLCK induces contraction of the perijunctional apical actomyosin ring in response to phosphorylation of the myosin light chain. Abnormal expression of MLCK has been observed in respiratory diseases, pancreatitis, cardiovascular diseases, cancer, and inflammatory bowel disease. The signaling pathways involved in MLCK activation and triggering of endothelial barrier dysfunction are discussed in this review. The pharmacological effects of regulating MLCK expression by inhibitors such as ML-9, ML-7, microbial products, naturally occurring products, and microRNAs are also discussed. The influence of MLCK in inflammatory diseases starts with endothelial barrier dysfunction. The effectiveness of anti-MLCK treatment may depend on alleviation of that primary pathological mechanism. This review summarizes evidence for the potential benefits of anti-MLCK agents in the treatment of inflammatory disease and the importance of avoiding treatment-related side effects, as MLCK is widely expressed in many different tissues.

  9. Potential for polyhydroxyalkanoate production on German or European municipal waste water treatment plants.

    Science.gov (United States)

    Pittmann, T; Steinmetz, H

    2016-08-01

    Biopolymers, which are made of renewable raw materials and/or biodegradable residual materials present a possible alternative to common plastic. A potential analysis, based on experimental results in laboratory scale and detailed data from German waste water treatment plants, showed that the theoretically possible production of biopolymers in Germany amounts to more than 20% of the 2015 worldwide biopolymer production. In addition a profound estimation regarding all European Union member states showed that theoretically about 115% of the actual worldwide biopolymer production could be produced on European waste water treatment plants. With an upgraded biopolymer production and a theoretically reachable biopolymer proportion of around 60% of the cell dry weight a total of 1,794,656tPHAa or approximately 236% of today's biopolymer production could be produced on waste water treatment plants in the European Union, using primary sludge as raw material only. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview

    Directory of Open Access Journals (Sweden)

    Xin-Hui Xie

    2015-04-01

    Full Text Available Steroid-associated osteonecrosis (SAON is a common orthopaedic problem caused by administration of corticosteroids prescribed for many nonorthopaedic medical conditions. We summarised different pathophysiologies of SAON which have adverse effects on multiple systems such as bone marrow stem cells (BMSCs pool, bone matrix, cell apoptosis, lipid metabolism, and angiogenesis. Different animal models were introduced to mimic the pathophysiology of SAON and for testing the efficacy of both prevention and treatment effects of various chemical drugs, biological, and physical therapies. According to the classification of SAON, several prevention and treatment methods are applied at the different stages of SAON. For the current period, Chinese herbs may also have the potential to prevent the occurrence of SAON. In the future, genetic analysis might also be helpful to effectively predict the development of ON and provide information for personalised prevention and treatment of patients with SAON.

  11. The interleukin (IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment.

    Science.gov (United States)

    Jethwa, H; Bowness, P

    2016-01-01

    Ankylosing spondylitis (AS), the most common form of spondyloarthropathy, is a chronic, progressive multi-system inflammatory disorder characteristically affecting the sacroiliac joints and axial skeleton. Although the exact mechanisms underlying the pathogenesis of AS remain to be elucidated, the presence of human leucocyte antigen (HLA)-B27 is known to markedly increase its risk of development. Current treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF) blockers. In recent years, the interleukin (IL)-23/IL-17 pathway has been shown to have significance in the pathogenesis of AS and treatment modalities targeting this pathway have been shown to be beneficial in various other inflammatory conditions. This review provides an overview of the IL-23/IL-17 pathway in the pathogenesis of AS and summarizes new potential treatments for AS and related inflammatory diseases. © 2015 British Society for Immunology.

  12. Low-Carbon Watershed Management: Potential of Greenhouse Gas Reductions from Wastewater Treatment in Rural Vietnam

    Science.gov (United States)

    Mohan, Geetha; Jian, Pu; Takemoto, Kazuhiko; Fukushi, Kensuke

    2016-01-01

    Currently in many cities and rural areas of Vietnam, wastewater is discharged to the environment without any treatment, which emits considerable amount of greenhouse gas (GHG), particularly methane. In this study, four GHG emission scenarios were examined, as well as the baseline scenario, in order to verify the potential of GHG reduction from domestic wastewater with adequate treatment facilities. The ArcGIS and ArcHydro tools were employed to visualize and analyze GHG emissions resulting from discharge of untreated wastewater, in rural areas of Vu Gia Thu Bon river basin, Vietnam. By applying the current IPCC guidelines for GHG emissions, we found that a reduction of GHG emissions can be achieved through treatment of domestic wastewater in the studied area. Compared with baseline scenario, a maximum 16% of total GHG emissions can be reduced, in which 30% of households existing latrines are substituted by Japanese Johkasou technology and other 20% of domestic wastewater is treated by conventional activated sludge. PMID:27699202

  13. Evaluation of Potentially Harmful Substances in Dried Sludge of Isfahan Wastewater Treatment Plants

    Directory of Open Access Journals (Sweden)

    Bijan Bina

    2004-05-01

    Thus, taking into account the potential risks caused by presence of heavy metals in sludge and for the control of processes of sludge treatment and disposal and also protect of environmental health and enhauncement of public health level, specially for farmers and consumers of raw crops, needs sampling and characterization of sludge. In the present research concentration of 11 heavy metals and potentially toxic elements in dried sludge of Isfahan South and North and Shahinshahr wastewater treatment plants were determined using standard methods. Samples have been taken from dried sludge of treatment plants, and been measured after being prepared through atomic absorption apparatus and were compared with EPA enacted standards in regulation 40 CFR part 503. As well, fertilizer value parameters of sludge were measured and were compared with standards and guidelines. The results showed that the average concentration of above elements in all three treatment plants, not exceeded from EPA standards, however, regarding the accumulative property of these elements and lack of necessary protective effects of EPA standards, in using these sludges in the agricultural soils, the necessary caution and care should be taken, in other uses of sludges, however, there is no limitation.

  14. An arsenical analogue of adenosine diphosphate.

    Science.gov (United States)

    Webster, D; Sparkes, M J; Dixon, H B

    1978-01-01

    An analogue of ADP was made in which the terminal phosphono-oxy group, -O-PO(OH)2, has been replaced by the arsonomethyl group, -CH2-AsO(OH)2. This compound cannot form a stable analogue of ATP because anhydrides of arsonic acids are rapidly hydrolysed, so that any enzyme that phosphorylates ADP and accepts this analogue as a substrate should release orthophosphate in its presence. The analogue proves to be a poor substrate for 3-phosphoglycerate kinase (V/Km is diminished by a factor of 10(2)-10(3)) and a very poor substrate for pyruvate kinase (V/Km is diminished by a factor of 10(5)-10(6)). No substrate action was detected with adenyl kinase and creatine kinase. PMID:204292

  15. International video project on natural analogues

    International Nuclear Information System (INIS)

    Guentensperger, Marcel

    1993-01-01

    A natural analogue can be defined as a natural process which has occurred in the past and is studied in order to test predictions about the future evolution of similar processes. In recent years, natural analogues have been used increasingly to test the mathematical models required for repository performance assessment. Analogues are, however, also of considerable use in public relations as they allow many of the principles involved in demonstrating repository safety to be illustrated in a clear manner using natural systems with which man is familiar. The international Natural Analogue Working Group (NAWG), organised under the auspices of the CEC, has recognised that such PR applications are of considerable importance and should be supported from a technical level. At the NAWG meeting in Pitlochry, Scotland (June 1990), it was recommended that the possibilities for making a video film on this topic be investigated and Nagra was requested to take the lead role in setting up such a project

  16. The Greenland Analogue Project. Yearly Report 2009

    International Nuclear Information System (INIS)

    2010-12-01

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

  17. The Greenland Analogue Project. Yearly Report 2009

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

  18. Therapeutic Potentials of Microalgae in the Treatment of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Tosin A. Olasehinde

    2017-03-01

    Full Text Available Current research is geared towards the discovery of new compounds with strong neuroprotective potential and few or no side effects compared to synthetic drugs. This review focuses on the potentials of extracts and biologically active compounds derived from microalgal biomass for the treatment and management of Alzheimer’s disease (AD. Microalgal research has gained much attention recently due to its contribution to the production of renewable fuels and the ability of alga cells to produce several secondary metabolites such as carotenoids, polyphenols, sterols, polyunsaturated fatty acids and polysaccharides. These compounds exhibit several pharmacological activities and possess neuroprotective potential. The pathogenesis of Alzheimer’s disease (AD involves complex mechanisms that are associated with oxidative stress, cholinergic dysfunction, neuronal damage, protein misfolding and aggregation. The antioxidant, anticholinesterase activities as well as the inhibitory effects of some bioactive compounds from microalgae extracts on β-amyloid aggregation and neuronal death are discussed extensively. Phytochemical compounds from microalgae are used as pharmaceuticals, nutraceuticals and food supplements, and may possess neuroprotective potentials that are relevant to the management and/or treatment of AD.

  19. Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment.

    Science.gov (United States)

    Richards, John R; Lapoint, Jeff M; Burillo-Putze, Guillermo

    2018-01-01

    Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated. An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin: Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1: Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits

  20. Gastric Ulcer Hemorrhage - a Potential Life-Threatening Complication of Intragastric Balloon Treatment of Obesity

    Directory of Open Access Journals (Sweden)

    Aleksandra Mojkowska

    2017-04-01

    Full Text Available Background: Some morbidly obese patients do not qualify for bariatric surgery due to general health contraindications. Intragastric balloon treatment might be a therapeutic option in the above-mentioned cases. It can prime super-obese patients with end-stage disease for bariatric surgery. As a neoadjuvant therapy before surgery, it leads to a downstage of the disease by preliminary weight reduction, to an improvement in general health and, in summary, to a reduction of the perioperative risk. It is generally considered to be a safe method. However, due to the wide range of possible complications and unusual symptoms after intragastric balloon treatment, an interdisciplinary, instead of only a surgical or endoscopic, treatment and follow-up might be recommended in these patients. Case Report: We here describe a potential life-threatening complication in the form of gastric bleeding as a consequence of intragastric balloon treatment and simultaneous aspirin taking and Helicobacter pylori infection. Conclusion: There have been reports of some complications of intragastric balloon treatment. However, to the best of our knowledge there were no reports concerning life-threatening hemorrhage from gastric ulcer.

  1. Artificial Red Blood Cells as Potential Photosensitizers in Dye Laser Treatment Against Port-Wine Stains.

    Science.gov (United States)

    Rikihisa, Naoaki; Watanabe, Shoji; Saito, Yoshiaki; Sakai, Hiromi

    2017-04-13

    We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments. As compared with human red blood cells, Hb-Vs have the same absorbance of 595 nm wavelength light and produce the same level of heat following dye laser irradiation. Small sized Hb-Vs (250 nm) distribute in the plasma phase in blood and tend to flow in the marginal zone of microvessels. Intravenous injections of Hb-Vs caused the dilatation of microvessels, and dye laser treatment with Hb-Vs destroyed the vessel wall effectively. Following the intravenous injection of Hb-Vs, the microvessels contained more Hb that absorbed laser photons and produced heat. This extra Hb tended to flow near the endothelial cells, which were the target of the laser treatment. These attributes of Hb-Vs will potentially contribute to enhancing the efficacy of dye laser treatment for port-wine stains. Hemoglobin is a type of porphyrin. Thus, our proposed treatment may have aspects of photodynamic therapy using porphyrin that leads to a cytotoxicity effect by active oxygen.

  2. Sulfonamides as Inhibitors ofLeishmania- Potential New Treatments for Leishmaniasis.

    Science.gov (United States)

    Katinas, Jade; Epplin, Rachel; Hamaker, Christopher; Jones, Marjorie A

    2017-04-01

    Leishmaniasis is an endemic disease caused by the protozoan parasite Leishmania. Current treatments for the parasite are limited by cost, availability and drug resistance as the occurrence of leishmaniasis continues to be more prevalent. Sulfonamides are a class of compounds with medicinal properties which have been used to treat bacterial and parasitic disease via various pathways especially as antimetabolites for folic acid. New derivatives of sulfonamide compounds were assessed for their impact on Leishmania cell viability and potential pathways for inhibition were evaluated. Leishmania tarentolae (ATCC Strain 30143) axenic promastigote cells were grown in brain heart infusion (BHI) medium and treated with varying concentrations of the new sulfonamide compounds. Light microscopy and viability tests were used to assess the cells with and without treatment. A non-water soluble sulfonamide was determined to have 90-96% viability inhibition 24 hours after treatment with 100 µM final concentration. Because Leishmania are also autotrophs for folate precursors, the folic acid pathway was identified as a target for sulfonamide inhibition. When folic acid was added to untreated Leishmania, cell proliferation increased. A water soluble derivative of the inhibitory sulfonamide was synthesized and evaluated, resulting in less viability inhibition with a single dose (approximately 70% viability inhibition after 24 hours with 100 µM final concentration), but additive inhibition with multiple doses of the compound. However, the potential mechanism of inhibition was different between the water-soluble and non-water soluble sulfonamides. The inhibitory effects and potential pathways of inhibition indicate that these compounds may be new treatments for this disease.

  3. Ozonation and Thermal Pre-Treatment of Municipal Sewage Sludge-Implications for Toxicity and Methane Potential

    DEFF Research Database (Denmark)

    Davidsson, A.; Eriksson, Eva; Fick, J.

    2013-01-01

    resulted in higher chemical oxygen demand (COD)-solubilisation, while the highest volatile fatty acids (VFA) increase was obtained with ozonation. Sludges had inhibiting effects in a barley seed germination assay and a yeast oestrogen screen both before and after pre-treatment, but inhibition was reduced......The aim of this study was to determine effects on methane potential and overall sludge quality from two different sludge pre-treatment technologies (ozonation high/low dosage and thermal treatment 55/70 degrees C). In general both treatments produced increased methane potential. Thermal treatment...... by ozone treatment and digestion. No statistical significant reduction in concentrations of included pharmaceuticals could be observed....

  4. Brain potentials measured during a Go/NoGo task predict completion of substance abuse treatment.

    Science.gov (United States)

    Steele, Vaughn R; Fink, Brandi C; Maurer, J Michael; Arbabshirani, Mohammad R; Wilber, Charles H; Jaffe, Adam J; Sidz, Anna; Pearlson, Godfrey D; Calhoun, Vince D; Clark, Vincent P; Kiehl, Kent A

    2014-07-01

    U.S. nationwide estimates indicate that 50% to 80% of prisoners have a history of substance abuse or dependence. Tailoring substance abuse treatment to specific needs of incarcerated individuals could improve effectiveness of treating substance dependence and preventing drug abuse relapse. We tested whether pretreatment neural measures of a response inhibition (Go/NoGo) task would predict which individuals would or would not complete a 12-week cognitive behavioral substance abuse treatment program. Adult incarcerated participants (n = 89; women n = 55) who volunteered for substance abuse treatment performed a Go/NoGo task while event-related potentials (ERPs) were recorded. Stimulus- and response-locked ERPs were compared between participants who completed (n = 68; women = 45) and discontinued (n = 21; women = 10) treatment. As predicted, stimulus-locked P2, response-locked error-related negativity (ERN/Ne), and response-locked error positivity (Pe), measured with windowed time-domain and principal component analysis, differed between groups. Using logistic regression and support-vector machine (i.e., pattern classifiers) models, P2 and Pe predicted treatment completion above and beyond other measures (i.e., N2, P300, ERN/Ne, age, sex, IQ, impulsivity, depression, anxiety, motivation for change, and years of drug abuse). Participants who discontinued treatment exhibited deficiencies in sensory gating, as indexed by smaller P2; error-monitoring, as indexed by smaller ERN/Ne; and adjusting response strategy posterror, as indexed by larger Pe. The combination of P2 and Pe reliably predicted 83.33% of individuals who discontinued treatment. These results may help in the development of individualized therapies, which could lead to more favorable, long-term outcomes. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  5. Recording of corticospinal evoked potential for optimum placement of motor cortex stimulation electrodes in the treatment of post-stroke pain.

    Science.gov (United States)

    Yamamoto, Takamitsu; Katayama, Yoichi; Obuchi, Toshiki; Kano, Toshikazu; Kobayashi, Kazutaka; Oshima, Hideki; Fukaya, Chikashi; Kakigi, Ryusuke

    2007-09-01

    The corticospinal motor evoked potential (MEP) evoked by motor cortex stimulation was investigated as an intraoperative index for the placement of stimulation electrodes in the epidural space over the motor cortex for the treatment of post-stroke pain. A grid of plate electrodes was placed in the epidural space to cover the motor cortex, sensory cortex, and premotor cortex employing a magnetic resonance imaging-guided neuronavigation system in two patients with severe post-stroke pain in the right extremities, a 66-year-old man with dysesthesia manifesting as burning and aching sensation, and a 67-year-old woman with dysesthesia manifesting as pricking sensation. The D-wave of the corticospinal MEP was recorded with a flexible wire electrode placed in the epidural space of the spinal cord during anodal monopolar stimulation of each plate electrode under general anesthesia. The grid electrode was fixed in position with dural sutures and the craniotomy closed. The effect of pain reduction induced by anodal monopolar stimulation of the same plate electrodes was examined using the visual analogue scale (VAS) on a separate day in the awake state without anesthesia. Comparison of the percentage VAS reduction and the recorded amplitude of the D-wave employing the same stimulation electrode revealed significant correlations in Case 1 (r = 0.828, p r = 0.807, p < 0.01). The grid electrode was then replaced with two RESUME electrodes over the hand and foot areas, and the optimum positions were identified by D-wave recording before electrode fixation. Both patients reported satisfactory pain alleviation with lower stimulation voltages than usually required for patients with similar symptoms. These results indicate the potential of D-wave recording as an intraoperative indicator for the placement of stimulating electrodes over the motor cortex for pain relief.

  6. The analogue method for precipitation prediction: finding better analogue situations at a sub-daily time step

    Science.gov (United States)

    Horton, Pascal; Obled, Charles; Jaboyedoff, Michel

    2017-07-01

    Analogue methods (AMs) predict local weather variables (predictands) such as precipitation by means of a statistical relationship with predictors at a synoptic scale. The analogy is generally assessed on gradients of geopotential heights first to sample days with a similar atmospheric circulation. Other predictors such as moisture variables can also be added in a successive level of analogy. The search for candidate situations similar to a given target day is usually undertaken by comparing the state of the atmosphere at fixed hours of the day for both the target day and the candidate analogues. This is a consequence of using standard daily precipitation time series, which are available over longer periods than sub-daily data. However, it is unlikely for the best analogy to occur at the exact same hour for the target and candidate situations. A better analogue situation may be found with a time shift of several hours since a better fit can occur at different times of the day. In order to assess the potential for finding better analogues at a different hour, a moving time window (MTW) has been introduced. The MTW resulted in a better analogy in terms of the atmospheric circulation and showed improved values of the analogy criterion on the entire distribution of the extracted analogue dates. The improvement was found to increase with the analogue rank due to an accumulation of better analogues in the selection. A seasonal effect has also been identified, with larger improvements shown in winter than in summer. This may be attributed to stronger diurnal cycles in summer that favour predictors taken at the same hour for the target and analogue days. The impact of the MTW on the precipitation prediction skill has been assessed by means of a sub-daily precipitation series transformed into moving 24 h totals at 12, 6, and 3 h time steps. The prediction skill was improved by the MTW, as was the reliability of the prediction. Moreover, the improvements were greater for days

  7. Recycling potential of air pollution control residue from sewage sludge thermal treatment as artificial lightweight aggregates.

    Science.gov (United States)

    Bialowiec, Andrzej; Janczukowicz, Wojciech; Gusiatin, Zygmunt M; Thornton, Arthur; Rodziewicz, Joanna; Zielinska, Magdalena

    2014-03-01

    Thermal treatment of sewage sludge produces fly ash, also known as the air pollution control residue (APCR), which may be recycled as a component of artificial lightweight aggregates (ALWA). Properties of APCR are typical: high content of Ca, Mg, P2O5, as well as potential to induce alkaline reactions. These properties indicate that ALWA prepared with a high content of APCR may remove heavy metals, phosphorus, and ammonium nitrogen from wastewater with high efficiency. The aim of this preliminary study was to determine the optimal composition of ALWA for potential use as a filter media in wastewater treatment systems. Five kinds of ALWA were produced, with different proportions of ash (shown as percentages in subscripts) in mixture with bentonite: ALWA0 (reference), ALWA12.5, ALWA25, ALWA50, and ALWA100. The following parameters of ALWA were determined: density, bulk density, compressive strength, hydraulic conductivity, and removal efficiency of ions Zn(2+), NH4 (+), and PO4 (3-). Tests showed that ALWA had good mechanical and hydraulic properties, and might be used in wastewater filtering systems. Phosphates and zinc ions were removed with high efficiency (80-96%) by ALWA25-100 in static (batch) conditions. The efficiency of ammonium nitrogen removal was low, <18%. Artificial wastewater treatment performance in dynamic conditions (through-flow), showed increasing removal efficiency of Zn(2+), PO4 (3-) with a decrease in flow rate.

  8. Characterization of aluminium-based water treatment residual for potential phosphorus removal in engineered wetlands

    International Nuclear Information System (INIS)

    Babatunde, A.O.; Zhao, Y.Q.; Burke, A.M.; Morris, M.A.; Hanrahan, J.P.

    2009-01-01

    Aluminium-based water treatment residual (Al-WTR) is the most widely generated residual from water treatment facilities worldwide. It is regarded as a by-product of no reuse potential and landfilled. This study assessed Al-WTR as potential phosphate-removing substrate in engineered wetlands. Results indicate specific surface area ranged from 28.0 m 2 g -1 to 41.4 m 2 g -1 . X-ray Diffraction, Fourier transform infrared and energy-dispersive X-ray spectroscopes all indicate Al-WTR is mainly composed of amorphous aluminium which influences its phosphorus (P) adsorption capacity. The pH and electrical conductivity ranged from 5.9 to 6.0 and 0.104 dS m -1 to 0.140 dS m -1 respectively, showing that it should support plant growth. Batch tests showed adsorption maxima of 31.9 mg P g -1 and significant P removal was achieved in column tests. Overall, results showed that Al-WTR can be used for P removal in engineered wetlands and it carries the benefits of reuse of a by-product that promotes sustainability. - Aluminium-based water treatment residual can be used for phosphorus removal in engineered wetlands!

  9. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Khanna IK

    2015-12-01

    Full Text Available Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed µ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other µ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.Keywords: buprenorphine, opioids, opioid dependence, partial agonist, hyperalgesia, neuropathic pain

  10. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  11. Vitamin D: potential in the prevention and treatment of lung cancer.

    Science.gov (United States)

    Norton, Rosemary; O'Connell, Maria A

    2012-01-01

    Vitamin D is a steroid hormone traditionally recognized for maintaining calcium and phosphorous homeostasis in the body. However, it is now widely accepted that it exerts several extraskeletal actions, including anti-tumorigenic and immunomodulatory effects in vitro and in vivo. There is now a huge interest in studying the modes of action of vitamin D in a wide range of infectious and chronic disease settings and its potential in cancer prevention and treatment is currently under detailed investigation. In relation to the lung, evidence from observational studies, animal models and in vitro cell culture suggest that vitamin D may play a beneficial role in pulmonary inflammation. In addition, an adequate vitamin D status may be important for lung cancer prevention. Furthermore, vitamin D or its analogs, alone or in combination with cytotoxics, have potential in the treatment of lung cancer. Vitamin D is converted to its active form locally in the lung, suggesting that it may play an important role in lung health. Here, we review the evidence from observational, clinical and experimental studies in relation to vitamin D and lung cancer. In addition, we discuss vitamin D resistance in lung tumors and the potential molecular mechanisms of vitamin D action in lung cancer cells.

  12. Natural analogue studies as supplements to biomineralization research

    International Nuclear Information System (INIS)

    McNeil, M.B.

    1995-01-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu 4 SO 4 (OH) 6· H 2 O] and mineral morphologies unusual in corrosion [malachite, Cu 2 CO 3 (OH) 2 , rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena

  13. Between Analogue and Digital Diagrams

    Directory of Open Access Journals (Sweden)

    Zoltan Bun

    2012-10-01

    Full Text Available This essay is about the interstitial. About how the diagram, as a method of design, has lead fromthe analogue deconstruction of the eighties to the digital processes of the turn of the millennium.Specifically, the main topic of the text is the interpretation and the critique of folding (as a diagramin the beginning of the nineties. It is necessary then to unfold its relationship with immediatelypreceding and following architectural trends, that is to say we have to look both backwards andforwards by about a decade. The question is the context of folding, the exchange of the analogueworld for the digital. To understand the process it is easier to investigate from the fields of artand culture, rather than from the intentionally perplicated1 thoughts of Gilles Deleuze. Both fieldsare relevant here because they can similarly be used as the yardstick against which the era itselfit measured. The cultural scene of the eighties and nineties, including performing arts, movies,literature and philosophy, is a wide milieu of architecture. Architecture responds parallel to itsera; it reacts to it, and changes with it and within it. Architecture is a medium, it has always beena medium, yet the relations are transformed. That’s not to say that technical progress, for exampleusing CAD-software and CNC-s, has led to the digital thinking of certain movements ofarchitecture, (it is at most an indirect tool. But the ‘up-to-dateness’ of the discipline, however,a kind of non-servile reading of an ‘applied culture’ or ‘used philosophy’2 could be the key.(We might recall here, parenthetically, the fortunes of the artistic in contemporary mass society.The proliferation of museums, the magnification of the figure of the artist, the existence of amassive consumption of printed and televised artistic images, the widespread appetite for informationabout the arts, all reflect, of course, an increasingly leisured society, but also relateprecisely to the fact

  14. Synthetic analogues of natural semiochemicals as promising insect control agents

    International Nuclear Information System (INIS)

    Ujvary, Istvan; Toth, Miklos; Guerin, Patrick

    2000-01-01

    After decades of research and development, insect pheromones and other semiochemicals became indispensable tools of ecologically based agricultural pest and disease vector management programmes with main uses as: 1) detection and population monitoring of emerging and migrating insects, 2) mass trapping of insects, 3) combined formulation of semiochemicals and insecticides ('lure-and-kill'), and 4) mating disruption with specially formulated pheromone components. In spite of their demonstrated safety and biodegradability, the direct application of these semiochemicals for pest control has not fulfilled initial expectations. Nonetheless considerable field experience has been accumulated (Carde and Minks 1995). Evidently, two important factors limit the practical potential of these substances: 1) inherent in their particular mode of action, semiochemicals, especially pheromones, are effectively cleared by specific enzymes in the insect antennae, and 2) some of these compounds contain labile functional moieties that are prone to degradation (oxidation, isomerisation and polymerisation) under field conditions. Appropriate chemical modifications of these natural compounds, however, can circumvent these problems by providing synthetic analogues (sometimes also called parapheromones or antipheromones; for early studies, see Roelofs and Comeau 1971, Payne et al. 1973) which in ideal cases are not only more potent and environmentally acceptable but more economical as well. It should also be mentioned that many effective attractants have been discovered through the empirical screening of synthetic chemicals, some of which have actually turned out to be structural relatives of natural semiochemicals of the particular insect. In this paper, selected case studies of analogues of sex pheromones and kairomones will be presented. The examples from our work include nitrile bioisosteres of labile aldehyde pheromone components of the cranberry girdler moth, Chrysoteuchia topiaria

  15. (18)F-labelled metomidate analogues as adrenocortical imaging agents.

    Science.gov (United States)

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Långström, Bengt

    2009-05-01

    Two- and one-step syntheses of (18)F-labelled analogues of metomidate, such as 2-[(18)F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[(18)F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[(18)F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[(18)F]fluoroethyl 4-methylbenzenesulfonate or 3-[(18)F]fluoropropyl 4-methylbenzenesulfonate. These were used as (18)F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46+/-3% and 79+/-30%, respectively. Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  16. Survey of potential improvements during the course of the radiotherapy treatment. A patient questionnaire

    International Nuclear Information System (INIS)

    Momm, Felix; Jooss, David; Adebahr, Sonja; Duncker-Rohr, Viola; Heinemann, Felix; Kirste, Simon; Messmer, Marc-Benjamin; Grosu, Anca-Ligia; Xander, Carola J.; Becker, Gerhild

    2011-01-01

    In the context of quality assurance, increasing demands are placed on the whole radiotherapy treatment process. The patients directly concerned generally do not realize most aspects of the quality assurance program (e.g., additional safety checks) during their daily therapy. It was the aim of this study to systematically ask patients about potential improvements during the course of radiotherapy treatment from their own perspective. In the defined time span (1 month), 624 radiotherapy patients (600 questionnaires were returned, 96.2%) were interviewed using a questionnaire newly developed to inquire about several aspects of their treatment. Furthermore, they were asked for their specific needs and suggestions for improvements that could be made during the course of radiotherapy treatment. Overall, the patients were satisfied with the course of their radiotherapy treatment and with patient care. As an example, about 90% agreed with the statement: ''My first contact with the radiation oncology unit proceeded with kindness and competence so that I was given the impression that I will be well cared for in this clinic.'' Considering the organization of the course of radiotherapy, a large majority of patients attached great value to set appointments for the therapy fractions. A main point of criticism was waiting times or delays caused by servicing or machine failures. Small, low cost improvements as music in the therapy room were considered as important as expensive measures (e.g., daylight in the therapy room). The patients emphasized the importance of staff friendliness. The situation of radiotherapy patients was, in general, satisfactory. Future improvements can be mainly expected from smooth organisation of both planning and treatment which can be achieved by electronic scheduling systems. Many results of the survey could be easily implemented in daily practice. In matters of organization radiation oncology with its complex procedures can be used as a model for

  17. Investigation of the potential role of preoperative chemotherapy in treatment for gastric cancer with outlet obstruction.

    Science.gov (United States)

    Jiao, Xuelong; Zhou, Yanbing

    2015-09-01

    Preoperative chemotherapy is currently recognized as the recommended treatment for advanced gastric cancer. Whether there is a role of preoperative chemotherapy in the treatment for advanced gastric cancer with gastric outlet obstruction (GOO) is unknown. In order to explore the potential feasibility of preoperative chemotherapy for advanced gastric cancer with GOO, and to encourage the probe into optimal treatment strategies for advanced gastric cancer with GOO in the current era of preoperative chemotherapy prevailing, a systematic literature search was conducted with a multistage process. The characteristics of the retrieved publications were summarized and the essential information was extracted. Only 11 studies associated with preoperative chemotherapy for advanced gastric cancer with GOO were identified. Among them, 9 were case reports, while the other 2 were research reports of retrospective studies. None were of prospective studies. The paucity of the literature in this field is a marked finding of the present study, which reports the emerging attempts at preoperative chemotherapy for advanced gastric cancer patients with GOO, as no high-quality data are available. The definite role of chemotherapy as an initial treatment for advanced gastric cancer patients with GOO remains unclear. Clinical trials are expected to be conducted in order to explore the feasibility, safety and efficacy of preoperative chemotherapy for advanced gastric cancer patients with GOO.

  18. Anaerobe Tolerance to Oxygen and the Potentials of Anaerobic and Aerobic Cocultures for Wastewater Treatment

    Directory of Open Access Journals (Sweden)

    M.T. Kato

    1997-12-01

    Full Text Available The anaerobic treatment processes are considered to be well-established methods for the elimination of easily biodegradable organic matter from wastewaters. Some difficulties concerning certain wastewaters are related to the possible presence of dissolved oxygen. The common belief is that anaerobes are oxygen intolerant. Therefore, the common practice is to use sequencing anaerobic and aerobic steps in separate tanks. Enhanced treatment by polishing off the residual biodegradable oxygen demand from effluents of anaerobic reactors, or the biodegradation of recalcitrant wastewater pollutants, usually requires sequenced anaerobic and aerobic bacteria activities. However, the combined activity of both bacteria can also be obtained in a single reactor. Previous experiments with either pure or mixed cultures showed that anaerobes can tolerate oxygen to a certain extent. The oxygen toxicity to methanogens in anaerobic sludges was quantified in batch experiments, as well as in anaerobic reactors. The results showed that methanogens have a high tolerance to oxygen. In practice, it was confirmed that dissolved oxygen does not constitute any detrimental effect on reactor treatment performance. This means that the coexistence of anaerobic and aerobic bacteria in one single reactor is feasible and increases the potentials of new applications in wastewater treatment

  19. Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds.

    Science.gov (United States)

    Marfia, Giovanni; Navone, Stefania Elena; Di Vito, Clara; Ughi, Nicola; Tabano, Silvia; Miozzo, Monica; Tremolada, Carlo; Bolla, Gianni; Crotti, Chiara; Ingegnoli, Francesca; Rampini, Paolo; Riboni, Laura; Gualtierotti, Roberta; Campanella, Rolando

    2015-01-01

    Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances.

  20. Potential Biomolecules and Current Treatment Technologies for Diabetic Foot Ulcer: an Overview.

    Science.gov (United States)

    Khashim, Zenith; Samuel, Shila; Duraisamy, Nallusamy; Krishnan, Kathiravan

    2017-05-18

    Diabetic foot ulceration remains a major challenge and is one of the most expensive and leading causes of major and minor amputations among patients with diabetic foot ulcer. Hence the purpose of this review is to emphasize on potential molecular markers involved in diabetic foot ulcer physiology, the efficacy of different types of dressing materials, adjunct therapy and newer therapeutic approach like nanoparticles for the treatment of diabetic foot ulcer. We conducted a systematic literature review search by using Pubmed and other web searches. The quality evidence of diabetic foot ulcer biomolecules and treatments was collected, summarized and compared with other studies. The present investigation suggested that impaired wound healing in diabetic patients is an influence of several factors. All the advanced therapies and foot ulcer dressing materials are not suitable for all types of diabetic foot ulcers, however more prospective follow ups and in vivo and in vitro studies are needed to draw certain conclusion. Several critical wound biomolecules have been identified and are in need to be investigated in diabetic foot ulcers. The application of biocompatible nanoparticles holds a promising approach for designing dressing materials for the treatment of diabetic foot ulcer. Understanding the cellular and molecular events and identifying the appropriate treatment strategies for different foot ulcer grades will reduce recurrence of foot ulcer and lower limb amputation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Common bean seeds quality during storage under treatments with potential repellent of aromatic plants

    Directory of Open Access Journals (Sweden)

    F.P. PACHECO

    Full Text Available ABSTRACT ndustrial chemicals that control pests in stored seed can cause damage to health by residual effects remaining in the grains. Studies of products with potential insecticide and repellent properties are required to decrease post-harvest losses. Thus, the aim of this study was to evaluate the quality and efficiency of seed treatment in beans stored under the following treatments: dried leaves and crushed laurel (Laurus nobilis L., rosemary (Rosmarinus officinalis L. and basil (Ocimum basilicum L., cinnamon powder (Cinnamomum zeylanicum Breyn and ground cloves (Syzygium aromaticum L. over eight months. An untreated control and a treatment with diatomaceous earth were used to compare the results. At the beginning and at 30 days, percentages of normal and abnormal seedlings as well as seeds that did not germinate, mass of onehundred seeds, water content and infested seeds were analyzed. At 210 and 240 days, free choice arena and repellency testswere conducted. Treatments did not affect germination, mass of 100 seeds or water content; however, all plants tested showed a repellent effect on the bean weevil.

  2. Potential use of an ultrasound antifouling technology as a ballast water treatment system

    Science.gov (United States)

    Estévez-Calvar, Noelia; Gambardella, Chiara; Miraglia, Francesco; Pavanello, Giovanni; Greco, Giuliano; Faimali, Marco; Garaventa, Francesca

    2018-03-01

    The aim of this study was to investigate, at a laboratory scale, the potentialities of an ultrasound-based treatment initially designed to eliminate fouling, as a ballast water treatment system. Therefore, early life stages of three different zooplanktonic species (Amphibalanus amphitrite, Brachionus plicatilis and Artemia salina) were exposed to ultrasound waves (20-22 kHz). The experimental set up included static assays with variations of time exposure (30 s, 60 s and 30 s on/60 s off/30 s on), material of tanks (stainless steel, galvanized steel and plastic) and position of the ultrasound source. Results showed that the treatment efficacy increased from 30 to 60 s and no differences were registered between 60 s-continuous exposure and pulse exposure. The highest efficacy was observed in Experiment I (metal-to-metal contact assay) with a mortality value of 93-95% for B. plicatilis and A. salina. It consisted of organisms located inside stainless steel tubes that were located in direct contact with the ultrasound source and treated for 60 s. Further, we found that, generally, A. amphitrite and B. plicatilis were the most resistant species to the ultrasound treatment whereas A. salina was the most sensitive. We further discuss that US may unlikely be used for commercial vessels, but may be used to treat ballast water in smaller ballast tanks as on board of mega yachts.

  3. Potential of the Dietary Antioxidants Resveratrol and Curcumin in Prevention and Treatment of Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Marc Diederich

    2010-10-01

    Full Text Available Despite considerable improvements in the tolerance and efficacy of novel chemotherapeutic agents, the mortality of hematological malignancies is still high due to therapy relapse, which is associated with bad prognosis. Dietary polyphenolic compounds are of growing interest as an alternative approach, especially in cancer treatment, as they have been proven to be safe and display strong antioxidant properties. Here, we provide evidence that both resveratrol and curcumin possess huge potential for application as both chemopreventive agents and anticancer drugs and might represent promising candidates for future treatment of leukemia. Both polyphenols are currently being tested in clinical trials. We describe the underlying mechanisms, but also focus on possible limitations and how they might be overcome in future clinical use – either by chemically synthesized derivatives or special formulations that improve bioavailability and pharmacokinetics.

  4. Biology and potential strategies for the treatment of GM2 gangliosidoses.

    Science.gov (United States)

    Chavany, C; Jendoubi, M

    1998-04-01

    The GM2 gangliosidoses are a group of heritable neurodegenerative disorders caused by excessive accumulation of the ganglioside GM2 owing to deficiency in beta-hexosaminidase activity. Tay-Sachs and Sandhoff diseases have similar clinical phenotypes resulting from a deficiency in human hexosaminidase alpha and beta subunits, respectively. The lack of treatment for GM2 gangliosidoses stimulated interest in developing animal models to understand the molecular mechanisms underlying the various forms of this disease and to test new potential therapies. In this review, we discuss the molecular biology of GM2 gangliosidoses and the different strategies that have been tested in animal models for the treatment of this genetic disorder, including gene transfer and cell engraftment of neural stem cells engineered to express the hexosaminidase isoenzymes.

  5. Potential Applications of Nanotechnology for the Diagnosis and Treatment of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Joshua eMcCarroll

    2014-01-01

    Full Text Available Despite improvements in our understanding of pancreatic cancer and the emerging concept of personalized medicine for the treatment of this disease, it is still the fourth most common cause of cancer death in the western world. It is established that pancreatic cancer is a highly heterogeneous disease with a complex tumor microenvironment. Indeed the extensive stroma surrounding the cancer cells has been shown to be important in promoting tumor growth and metastases, as well as sequestering chemotherapeutic agents consequently decreasing delivery to the tumor cells. Nanotechnology has come to the forefront in the areas of medical diagnostics, imaging, and therapeutic drug delivery. This review will focus on the potential applications of nanotechnology for diagnosis, imaging, and delivery of therapeutic agents for the treatment of pancreatic cancer.

  6. Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer's disease.

    Science.gov (United States)

    Percy, Maire E; Kruck, Theo P A; Pogue, Aileen I; Lukiw, Walter J

    2011-11-01

    In 1991, treatment with low dose intramuscular desferrioxamine (DFO), a trivalent chelator that can remove excessive iron and/or aluminum from the body, was reported to slow the progression of Alzheimer's disease (AD) by a factor of two. Twenty years later this promising trial has not been followed up and why this treatment worked still is not clear. In this critical interdisciplinary review, we provide an overview of the complexities of AD and involvement of metal ions, and revisit the neglected DFO trial. We discuss research done by us and others that is helping to explain involvement of metal ion catalyzed production of reactive oxygen species in the pathogenesis of AD, and emerging strategies for inhibition of metal-ion toxicity. Highlighted are insights to be considered in the quests to prevent potentially toxic effects of aluminum toxicity and prevention and intervention in AD. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Bay laurel (Laurus nobilis) as potential antiviral treatment in naturally BQCV infected honeybees.

    Science.gov (United States)

    Aurori, Adriana C; Bobiş, Otilia; Dezmirean, Daniel S; Mărghitaş, Liviu A; Erler, Silvio

    2016-08-15

    Viral diseases are one of the multiple factors associated with honeybee colony losses. Apart from their innate immune system, including the RNAi machinery, honeybees can use secondary plant metabolites to reduce or fully cure pathogen infections. Here, we tested the antiviral potential of Laurus nobilis leaf ethanolic extracts on forager honeybees naturally infected with BQCV (Black queen cell virus). Total viral loads were reduced even at the lowest concentration tested (1mg/ml). Higher extract concentrations (≥5mg/ml) significantly reduced virus replication. Measuring vitellogenin gene expression as an indicator for transcript homeostasis revealed constant RNA levels before and after treatment, suggesting that its expression was not impacted by the L. nobilis treatment. In conclusion, plant secondary metabolites can reduce virus loads and virus replication in naturally infected honeybees. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Therapeutic Potential of Cholera Toxin B Subunit for the Treatment of Inflammatory Diseases of the Mucosa

    Directory of Open Access Journals (Sweden)

    Joshua M. Royal

    2017-11-01

    Full Text Available Cholera toxin B subunit (CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Furthermore, we recently found that a variant of CTB could induce colon epithelial wound healing in mouse colitis models. This review summarizes the possible mechanisms behind CTB’s anti-inflammatory activity and discuss how the protein could impact mucosal inflammatory disease treatment.

  9. Systemic BRAF/MEK Inhibitors as a Potential Treatment Option in Metastatic Conjunctival Melanoma.

    Science.gov (United States)

    Mor, Joel M; Heindl, Ludwig M

    2017-07-01

    In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma. The study provides a PubMed literature review. Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy. The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.

  10. Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shailendra Giri

    Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

  11. Assessment of potential greenhouse gas mitigation of available household solid waste treatment technologies

    Directory of Open Access Journals (Sweden)

    Hoang Minh Giang

    2013-11-01

    Full Text Available Current household solid waste treatment practices in most cities in Vietnam caused a great amount of direct greenhouse gas (GHG emissions. Available solid waste treatment technologies should be seriously taken  into consideration as a wedge of GHG mitigation in waste sector base on presently Vietnamese economic conditions. This study aim to evaluate the potential amount of GHG mitigation from current domestic solid waste treatment technologies in Vietnam including landfills and composting from various management scenarios. In oder to use Tier 2 model of IPCC 2006 for GHG estimation from landfills, an analysis on current household solid waste management system of the city was obtained by using material flow analysis approach. A case study in Hanoi, the capital city of Vietnam was carried out in this research. As a result, there was a reduced of over 70% of the amount of CH4 emissions and  up to 53% of total GHG saving (CO2-eq from avoiding organic waste to landfill. In addition, applying an energy recovery from LFG system to available landfills would lead to aproximately 75% of GHG saved compare to current emission of waste sector.Doi: http://dx.doi.org/10.12777/wastech.1.1.10-16Citation: Giang, H.M.,Luong, N.D., and Huong, L.T.M.2013. Assessment of potential greenhouse gas mitigation of available household solid waste treatment technologies. . Waste Technology 1(1:6-9. Doi: http://dx.doi.org/10.12777/wastech.1.1.10-16

  12. [The potential of general magnetic therapy for the treatment and rehabilitation (a review)].

    Science.gov (United States)

    Kulikov, A G; Voronina, D D

    2016-01-01

    This paper was designed to describe the main characteristics of general magnetic therapy and the mechanisms underlying its biological and therapeutic action. Special attention is given to the extensive application of this method in the routine clinical practice. The publications in the current scientific literature are reviewed in order to evaluate the potential of general magnetic therapy as a component of the combined treatment of various somatic pathologies, rehabilitation of the patients after surgical intervention with special reference to the management of the patients presenting with the oncological problems. The data suggesting good tolerability and high therapeutic effectiveness of the physiotherapeutic method under consideration.

  13. A maximum principle for the first-order Boltzmann equation, incorporating a potential treatment of voids

    International Nuclear Information System (INIS)

    Schofield, S.L.

    1988-01-01

    Ackroyd's generalized least-squares method for solving the first-order Boltzmann equation is adapted to incorporate a potential treatment of voids. The adaptation comprises a direct least-squares minimization allied with a suitably-defined bilinear functional. The resulting formulation gives rise to a maximum principle whose functional does not contain terms of the type that have previously led to difficulties in treating void regions. The maximum principle is derived without requiring continuity of the flux at interfaces. The functional of the maximum principle is concluded to have an Euler-Lagrange equation given directly by the first-order Boltzmann equation. (author)

  14. Modulation of the Kynurenine Pathway for the Potential Treatment of Neurodegenerative Diseases

    Science.gov (United States)

    Courtney, Stephen; Scheel, Andreas

    Modulation of tryptophan metabolism and in particular the kynurenine pathway is of considerable interest in the discovery of potential new treatments for neurodegenerative diseases. A number of small molecule inhibitors of the kynurenine metabolic pathway enzymes have been identified over recent years; a summary of these and their utility has been reviewed in this chapter. In particular, inhibitors of kynurenine monooxygenase represent an opportunity to develop a therapy for Huntington's disease; progress in the optimization of small molecule inhibitors of this enzyme is also described.

  15. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    Science.gov (United States)

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  16. Some potential strategies for the treatment of waste uranium metal and uranium alloys

    International Nuclear Information System (INIS)

    Burns, C.J.; Frankcom, T.M.; Gordon, P.L.; Sauer, N.N.

    1993-01-01

    Large quantities of uranium metal chips and turnings stored throughout the DOE Complex represent a potential hazard, due to the reactivity of this material toward air and water. Methods are being sought to mitigate this by conversion of the metal, via room temperature solutions routes, to a more inert oxide form. In addition, the recycling of uranium and concomitant recovery of alloying metals is a desirable goal. The emphasis of the authors' research is to explore a variety of oxidation and reduction pathways for uranium and its compounds, and to investigate how these reactions might be applied to the treatment of bulk wastes

  17. Potential role for therapies targeting DKK1, LRP5, and serotonin in the treatment of osteoporosis.

    Science.gov (United States)

    Zhang, Wei; Drake, Matthew T

    2012-03-01

    Osteoporosis is a common disorder in which diminished bone mass leads to progressive microarchitectural skeletal deterioration and increased fracture risk. Our understanding of both normal and pathologic bone biology continues to evolve, and with it our grasp of the highly coordinated relationships between primary bone cells (osteoblasts, osteoclasts, and osteocytes) and the complex molecular signals bone cells use to integrate signals derived from other organ systems, including the immune, hematopoietic, gastrointestinal, and central nervous systems. It is now clear that the Wnt signaling pathway is central to regulation of both skeletal modeling and remodeling. Herein, we discuss components of the Wnt signaling pathway (DKK1, an endogenous soluble inhibitor of Wnt signaling) and LRP5 (a plasma membrane-localized Wnt co-receptor) as potential future targets for osteoporosis therapy. Finally, we discuss the current controversial role for serotonin in skeletal metabolism, and the potential role of future therapies targeting serotonin for osteoporosis treatment.

  18. A novel peptide sansalvamide analogue inhibits pancreatic cancer cell growth through G0/G1 cell-cycle arrest

    International Nuclear Information System (INIS)

    Ujiki, Michael B.; Milam, Ben; Ding Xianzhong; Roginsky, Alexandra B.; Salabat, M. Reza; Talamonti, Mark S.; Bell, Richard H.; Gu Wenxin; Silverman, Richard B.; Adrian, Thomas E.

    2006-01-01

    Patients with pancreatic cancer have little hope for cure because no effective therapies are available. Sansalvamide A is a cyclic depsipeptide produced by a marine fungus. We investigated the effect of a novel sansalvamide A analogue on growth, cell-cycle phases, and induction of apoptosis in human pancreatic cancer cells in vitro. The sansalvamide analogue caused marked time- and concentration-dependent inhibition of DNA synthesis and cell proliferation of two human pancreatic cancer cell lines (AsPC-1 and S2-013). The analogue induced G0/G1 phase cell-cycle arrest and morphological changes suggesting induction of apoptosis. Apoptosis was confirmed by annexin V binding. This novel sansalvamide analogue inhibits growth of pancreatic cancer cells through G0/G1 arrest and induces apoptosis. Sansalvamide analogues may be valuable for the treatment of pancreatic cancer

  19. Risedronate once monthly: a potential new regimen for the treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    María J Moro-Álvarez

    2008-06-01

    Full Text Available María J Moro-Álvarez1, Manuel Díaz-Curiel21Hospital Central Cruz Roja, Madrid, 2Fundación Jiménez Díaz, Madrid, Spain, Internal Medicine, Metabolic Bone Disease UnitAbstract: Postmenopausal osteoporosis increases susceptibility to low-trauma fractures due to reduced bone volume and microarchitectural deterioration. Daily nitrogen-containing bisphosphonates have shown antifracture efficacy in many studies and are the most commonly prescribed treatment for women with postmenopausal osteoporosis. However, optimal efficacy is often not achieved due to poor patient adherence to medication. Current dosing schedules are often inconvenient or impractical for patients. Poor adherence increases risk of fracture, which itself increases morbidity, healthcare costs and, potentially, mortality. Although weekly rather than daily dosing of bisphosphonates has improved adherence, significant problems remain. Efforts to reduce dosing frequency as a possible means for further improving adherence (compliance and persistence, and therefore treatment outcomes, are ongoing. Risedronate, a third-generation bisphosphonate, has been shown in multiple clinical trials to reduce fracture risk and improve bone mineral density in postmenopausal women with osteoporosis. Risedronate has a specific structure and set of characteristics that enable less frequent dosing. This paper reviews the structure of risedronate, and how this translates into high antiresorptive potency, favorable bone binding, persistence in bone, and good tolerability that permits less frequent dosing. The paper also reviews the clinical evidence for risedronate, demonstrating the viability of less frequent dosing, with its potential benefits for patient convenience and adherence to therapy. Two equivalence or non-inferiority bridging studies have demonstrated the option of novel risedronate dosing regimens. These studies are reviewed to demonstrate the efficacy and safety of two different monthly

  20. A fuel treatment reduces potential fire severity and increases suppression efficiency in a Sierran mixed conifer forest

    Science.gov (United States)

    Jason J. Moghaddas

    2006-01-01

    Fuel treatments are being widely implemented on public and private lands across the western U.S. While scientists and managers have an understanding of how fuel treatments can modify potential fire behavior under modeled conditions, there is limited information on how treatments perform under real wildfire conditions in Sierran mixed conifer forests. The Bell Fire...

  1. Effects of thermal pre-treatments on solid slaughterhouse waste methane potential.

    Science.gov (United States)

    Rodríguez-Abalde, A; Fernández, B; Silvestre, G; Flotats, X

    2011-07-01

    The effects of thermal pre-treatments on the biogas production potential of two solid slaughterhouse waste types (poultry and piggery slaughterhouse by-products) were assessed by means of batch experiments. Both animal by-products were characterized in terms of fat, protein and carbohydrate concentrations. The selected thermal pre-treatments, pasteurization (70 °C for 60 min) and sterilization (133 °C and 3 bars for 20 min), are included in the current European regulations for the disposal or use of animal by-products. The pre-treatments produced notable improvements in organic matter solubilization, but had different effects on the anaerobic bioavailability of the treated substrates. The methane yield of the initial volatile solids did not increase significantly after pre-treatment when carbohydrate concentration was high, reaching a maximum of 0.48 m(CH4)(3) kg(VS)(-1) for the pasteurized poultry waste. However, this yield increased by up to 52.7% after pasteurization and 66.1% after sterilization for the lower carbohydrate concentration sample (piggery waste), reaching maxima of 0.88 and 0.96 m(CH4)(3) kg(VS)(-1), respectively. The maximum methane production rates, measured as the maximum slope of the accumulated methane production curve, per unit of initial biomass content, were also different. While this rate increased by 52.6% and 211.6% for piggery waste after pasteurization and sterilization, respectively, it decreased by 43.8% for poultry waste after pasteurization with respect to untreated waste. Compounds with low biodegradability that are produced by Maillard reactions during thermal pre-treatment could explain the low bioavailability observed for waste with a high carbohydrate concentration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Characterization of haloacetaldehyde and trihalomethane formation potentials during drinking water treatment.

    Science.gov (United States)

    Mao, Yu-Qin; Wang, Xiao-Mao; Guo, Xian-Fen; Yang, Hong-Wei; Xie, Yuefeng F

    2016-09-01

    Haloacetaldehydes (HAs) are the third prevalent group of disinfection by-products (DBPs) of great health concern. In this study, their formation and speciation during chlorination were investigated for raw and process waters collected at three O3-biological activated carbon (BAC) advanced drinking water treatment plants. The results showed that all HA formation potentials (HAFPs) were highly enhanced whenever ozone was applied before or after conventional treatment. Sand filtration and BAC filtration could substantially reduce HAFPs. Trihalomethanes (THMs) were also measured to better understand the role of HAs in DBPs. Very different from HAFPs, THMFPs kept decreasing with the progress of treatment steps, which was mainly attributed to the different precursors for HAs and THMs. Brominated HAs were detected in bromide-containing waters. Chloral hydrate (CH) contributed from 25% to 48% to the total HAs formed in waters containing 100-150 μg L(-1) bromide, indicating the wide existence of other HAs after chlorination besides CH production. In addition, bromide incorporation factor (BIF) in HAs and THMs increased with the progress of treatment steps and the BIF values of THMs were generally higher than those of HAs. The BAC filtration following ozonation could significantly reduce HA precursors produced from ozonation but without complete removal. The brominated HAFPs in the outflow of BAC were still higher than their levels in the raw water. As a result, O3-BAC combined treatment was effective at controlling the total HAs, whereas it should be cautious for waters with high bromide levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis.

    Science.gov (United States)

    Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W

    2016-07-01

    Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  5. Estrogenic activity and identification of potential xenoestrogens in a coking wastewater treatment plant.

    Science.gov (United States)

    Zhao, Jian-Liang; Chen, Xiao-Wen; Yan, Bo; Wei, Chaohai; Jiang, Yu-Xia; Ying, Guang-Guo

    2015-02-01

    In this study, the estrogenic activities in influent and effluents of coking wastewater from different treatment stages were studied using Yeast Estrogen Screen (YES) bioassays. Raw extracts were further fractioned to identify the potential xenoestrogens combined with YES bioassays and gas chromatography-mass spectrometry analysis. Influent, primary effluent, and anaerobic effluent showed high estrogenic activities, with potencies of 1136±269, 1417±320, and 959±69 ng/L of 17β-estradiol (E2) equivalent (EEQ), respectively. The potency of estrogenic activity was gradually removed through the treatment processes. In the final effluent, the estrogenic activity was reduced to 0.87 ng EEQ/L with a total removal efficiency of more than 99%, suggesting that the estrogenic activity was almost completely removed in the coking wastewater. For the fractions of raw extracts, bioassay results showed that the estrogenic activities were mostly present in the polar fractions. Correlation analysis between estrogenic activities and responses of identified chemicals indicated that potential xenoestrogens were the derivatives of indenol, naphthalenol, indol, acridinone, fluorenone, and carbazole. The estrogenic activity in the final effluent was higher than the predicted no effect concentration (PNEC) for E2, implying that the discharged effluent would probably exert estrogenic activity risk to the aquatic ecosystem in "the worst-case scenario." Copyright © 2014. Published by Elsevier Inc.

  6. Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments.

    Science.gov (United States)

    Jin, Faguang; Li, Congcong

    2017-06-01

    Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration.

  7. Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer's Disease Treatment: An In Vitro Study

    Science.gov (United States)

    Ahmed, Nermeen El-Moataz Bellah; Murakami, Masashi; Hirose, Yujiro; Nakashima, Misako

    2016-01-01

    The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer's disease (AD) is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs) to reduce cytotoxicity and apoptosis caused by amyloid beta (Aβ) peptide. We determined whether DPSCs can secrete the Aβ-degrading enzyme, neprilysin (NEP), and evaluated the effects of NEP expression in vitro by quantitating Aβ-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Aβ peptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degrading Aβ 1–42 in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer's disease. PMID:27403169

  8. Reduction of potential respiratory pathogens by oral hygienic treatment in patients undergoing endotracheal anesthesia.

    Science.gov (United States)

    Okuda, Minori; Kaneko, Yuzuru; Ichinohe, Tatsuya; Ishihara, Kazuyuki; Okuda, Katsuji

    2003-01-01

    This study was conducted to evaluate the usefulness of mechanical and chemical prophylactic oral cleansing treatments for reducing potential respiratory pathogens existing in the oral cavity. Thirty-two patients scheduled to undergo oral and maxillofacial surgery that required endotracheal anesthesia were randomly allocated to one of the two groups, the oral cleansing group (n = 16) or the noncleansing group (n = 16). Culture and polymerase chain reaction (PCR) methods were used to detect and enumerate pathogens. Oral cleansing was carried out with an electric toothbrush capable of automatically supplying and aspirating povidone-iodine solution before surgery, followed by rinsing twice a day after surgery. Cephazolin (3 g x day(-1)) was given to all patients for 5 days after surgery. The PCR detection rates of Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Porphyromonas gingivalis in gargle samples before treatment were 87.5%, 68.8%, 53.1%, and 40.6%, respectively. Oral cleansing reduced the detection rates and numbers of methicillin-sensitive Staphylococcus species, S. pneumoniae, and H. influenzae. In contrast, there was no significant reduction of methicillin-resistant Staphylococcus species, S. pneumoniae, H. influenzae, or P. aeruginosa in subjects who underwent systemic cephazolin administration without oral cleansing. The combination of mechanical and chemical oral cleansing resulted in a significant reduction of potential respiratory pathogens in the oral cavity.

  9. Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments

    Science.gov (United States)

    Jin, Faguang; Li, Congcong

    2017-01-01

    Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration. PMID:28587319

  10. Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

    Directory of Open Access Journals (Sweden)

    Dürsteler KM

    2015-06-01

    Full Text Available Kenneth M Dürsteler,1,2 Eva-Maria Berger,1 Johannes Strasser,1 Carlo Caflisch,2 Jochen Mutschler,2 Marcus Herdener,2 Marc Vogel1 1Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland; 2Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Background: Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH, as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim: To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods: We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results: MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and

  11. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    Directory of Open Access Journals (Sweden)

    B S Jackson

    2017-04-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA. To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  12. Conversion of sewage treatment plants on sludge digestion. Energetic and economic optimization potential

    International Nuclear Information System (INIS)

    Schmitt, Theo G.; Gretzschel, Oliver

    2014-03-01

    Investigations within the framework of the state-commissioned project ''Re-evaluation of wastewater purification plants with anaerobic sludge treatment with due consideration to framework conditions in terms of the energy and the wastewater management situation in Rhineland-Palatinate'', abbreviated ''NAwaS'', have shown that due to the rise in energy prices and availability of innovative techniques and methods it can be economically efficient, from a plant capacity of 10,000 inhabitants upwards, to convert sewage treatment plants to sludge digestion. Findings from the NAwaS project show the state of Rhineland-Palatinate to have a large potential for the conversion of sewage treatment plants to sludge digestion. Depending on the rate of price increase as well as interest rates the use of digester gas could permit an increase in electricity output by up to 50% over today's levels. Moreover, converted plants would be able to almost completely cover their own heat demand and in addition permit energy savings totalling an expected 5 kWh/(inhabitant x a). If one incorporates the possibilities offered by the procurement of sludge or suitable co-substrates from outside sources, by retrofitting sewage plants with combined heat and power stations or micro gas turbines as well as by process optimisation in existing digestion plants, this gives a further significant increase in potential production capacity and hence economic efficiency. In some of the sewage plants the above measures for saving energy and boosting energy production will even lead to energy self-sufficiency. [de

  13. Photodynamic therapy in the treatment of epithelial potentially malignant disorders of the mouth: advantages and disadvantages

    Science.gov (United States)

    Gaimari, G.; Russo, C.; Palaia, G.; Tenore, G.; Del Vecchio, A.; Romeo, U.

    2016-03-01

    Introduction: Leukoplakia is a potentially malignant epithelial lesion with carcinomatous percentages transformation comprehended between 1% and 7% for the homogeneous forms and from 4% to 15% for the non-homogeneous ones. Their removal can be performed by scalpel or laser surgery (excision or vaporization). Photodynamic therapy (PDT) is a bloodless treatment option, based on the involvement of three elements: light, photosensitizer and oxygen. When the molecules of the photosensitizer are activated by a low power laser, energy is transferred to molecular oxygen creating highly reactive radicals of oxygen, that have a cytotoxic effect on target cells. Aim of the study: According to several studies in Literature, it has been decided to evaluate through an initial clinical trial, the efficacy of PDT using topical aminolevulinic acid (5-ALA) activated by a laser diode (λ = 635 nm) to treat potentially oral malignant lesions and to illustrate the advantages and disadvantages derived from the use of this technique. Materials and Methods: Five patients, affected by oral leukoplakia (OL) and oral verrucous leukoplakia (OVL) on the mucosal cheeks, labial commissure, fornix and retromolar areas, have been treated using the PDT. Irradiation time with Diode laser: 1000s. Irradiation mode: Scanning. 5 cycles of 3 minute + final cycle of 100 seconds. Each cycle has been interrupted by pauses of 3 minutes. Results and conclusion: PDT results to be effective in the treatment of OL, especially on OVL. In fact, OVL, due to its irregularity, has got an area of increased retention for the gel that is more difficult to be removed by salivary flow. This could explain the better results obtained in this case rather than in those ones of OL. Furthermore, the advantages have been represented by: less invasivity, high sensitivity for altered tissues, minimal scar tissue, less side effects and no pain during and after operation. In contrast to this, the disadvantages were: longer treatment

  14. Review of daclizumab and its therapeutic potential in the treatment of relapsing–remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Reardon J

    2013-10-01

    Full Text Available Jennifer Reardon,1 Jai S Perumal1,2 1Weill Cornell MS Center at Nyack Hospital, Nyack Hospital, Nyack, NY, USA; 2Department of Neurology, Weill Cornell Medical College, New York, NY, USA Abstract: Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system. It can present in several forms, with the relapsing–remitting pattern being the most common. Since the approval of the first disease-modifying therapy and the initiation of appropriate treatments from the early stages of the disease, there seem to be positive impacts on the long-term outcomes and disability associated with MS. Currently, there are ten approved drugs for the treatment of MS, and several more are in various stages of development. These medications each have their unique profile in terms of efficacy, dose, routes of administration, tolerability, and adverse effects. Daclizumab is a humanized monoclonal antibody that is being explored for the treatment of MS. It is currently approved for use in allograft renal transplantation. Given its modulatory effects on the immune system, daclizumab's potential for use in MS was tested in extensive Phase II trials. With continued demonstration of its efficacy, it is currently in a Phase III trial for relapsing–remitting MS. While daclizumab has demonstrated beneficial effects in controlling disease activity in MS, there were also some safety and tolerability concerns that were raised. Further information from the ongoing Phase III trial, and from open-label studies, will shed light on the benefit and risk profile of this drug and its potential for use in MS. Keywords: multiple sclerosis, disease-modifying therapy, monoclonal antibodies, daclizumab, clinical trials

  15. Potential Risk Factors Associated With Vascular Diseases in Patients Receiving Treatment for Hypertension.

    Science.gov (United States)

    Kim, Hyunjung; Park, Joonhong; Chae, Hyojin; Lee, Gun Dong; Lee, Sang Yoon; Lee, Jong Min; Oh, Yong Seog; Kim, Myungshin; Kim, Yonggoo

    2016-05-01

    Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment. A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. Prothrombin G20210A, Factor V G1691A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were analyzed. All patients revealed wild type prothrombin G20210A and Factor V G1691A polymorphisms. The frequency of MTHFR polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The MTHFR 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, P=0.05). The group A demonstrated significantly higher Hcy levels (P=0.009), fibrinogen (P=0.004), and platelet counts (P=0.04) than group C. Group B had significantly higher levels of D-dimers (P=0.0001), platelet count (P=0.0002), and aCL (P=0.02) frequency than group C. The MTHFR 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them.

  16. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

    Science.gov (United States)

    Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.

    2011-01-01

    The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160

  17. Endodontic treatment enhances the regenerative potential of teeth with advanced periodontal disease with secondary endodontic involvement.

    Science.gov (United States)

    Kwon, Eun-Young; Cho, Yunjung; Lee, Ju-Youn; Kim, Sung-Jo; Choi, Jeomil

    2013-06-01

    The aim of this study was to identify a role for endodontic intervention in enhancing the regenerative potential of the periodontal ligament when combined with periodontal treatment in seriously involved teeth with a secondary endodontic component. Patients who exhibited radiolucency extending to the periapical region, abnormal electric pulp testing values, and deep probing depth derived from primary periodontal disease with secondary endodontic involvement were included. Intentional root canal treatment was applied to those teeth in which the apical lesions were presumed to communicate with those of the periodontal lesion of the teeth that remained vital. In all three selected cases, regenerative periodontal therapy incorporating either bone graft or guided tissue regeneration was instituted 3 months after the endodontic intervention. Remarkable enhancement in radiographic density was noticeable around the affected teeth as evidenced by changes in radiopacity. There was a significant reduction in the probing pocket depth and gain in the clinical attachment level. Chewing discomfort gradually disappeared from the commencement of the combined treatment. An intentional endodontic intervention may be a worthwhile approach for the sophisticated management of teeth suffering from serious attachment loss and alveolar bone destruction with concomitant secondary endodontic involvement.

  18. Studies of magnetic alginate-based electrospun matrices crosslinked with different methods for potential hyperthermia treatment.

    Science.gov (United States)

    Chen, Yen-Hsuan; Cheng, Chi-Hui; Chang, Wan-Ju; Lin, Yi-Ching; Lin, Feng-Huei; Lin, Jui-Che

    2016-05-01

    The magnetic electrospun mats were lately established as an innovative biomaterial for hyperthermic cancer treatment. Unlike those surface-modified magnetic nanoparticles that may not firmly adhere onto the tumor for long-term duration, the magnetic mats with nanofibrous structure can promote cell adhesion and kill the tumor directly within an alternating magnetic field. However, most magnetic electrospun mats were fabricated using non-biodegradable polymers and organic solvents, causing the problems of removal after therapy and the suspected biotoxicity associated with residual solvent. Alginate (SA) was utilized in this investigation as the main material for electrospinning because of being biodegradable and water-soluble. The alginate-based electrospun mats were then treated by an ionic or a covalent crosslinking method, and then followed by chelation with Fe(2+)/Fe(3+) for chemical coprecipitation of Fe3O4 magnetic nanoparticles. Significant less cytotoxicity was noted on both liquid extracts from the ionic-crosslinked (Fe3O4-SA/PEO) and covalent-crosslinked (Fe3O4-SA/PVA) magnetic electrospun mats as well as the surface of Fe3O4-SA/PVA. In vitro hyperthermia assay indicated that the covalent-crosslinked magnetic alginate-based mats reduced tumor cell viability greater than Fe3O4 nanoparticles. Such magnetic electrospun mats are of potential for hyperthermia treatment by endoscopic/surgical delivery as well as serving as a supplementary debridement treatment after surgical tumor removal. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Antimicrobial Photodynamic Therapy: Study of Bacterial Recovery Viability and Potential Development of Resistance after Treatment

    Directory of Open Access Journals (Sweden)

    Eliana Alves

    2010-01-01

    Full Text Available Antimicrobial photodynamic therapy (aPDT has emerged in the clinical field as a potential alternative to antibiotics to treat microbial infections. No cases of microbial viability recovery or any resistance mechanisms against it are yet known. 5,10,15-tris(1-Methylpyridinium-4-yl-20-(pentafluorophenyl-porphyrin triiodide (Tri-Py+-Me-PF was used as photosensitizer. Vibrio fischeri and recombinant Escherichia coli were the studied bacteria. To determine the bacterial recovery after treatment, Tri-Py+-Me-PF (5.0 µM was added to bacterial suspensions and the samples were irradiated with white light (40 W m-2 for 270 minutes. Then, the samples were protected from light, aliquots collected at different intervals and the bioluminescence measured. To assess the development of resistance after treatment, bacterial suspensions were exposed to white light (25 minutes, in presence of 5.0 μM of Tri-Py+-Me-PF (99.99% of inactivation and plated. After the first irradiation period, surviving colonies were collected from the plate and resuspended in PBS. Then, an identical protocol was used and repeated ten times for each bacterium. The results suggest that aPDT using Tri-Py+-Me-PF represents a promising approach to efficiently destroy bacteria since after a single treatment these microorganisms do not recover their viability and after ten generations of partially photosensitized cells neither of the bacteria develop resistance to the photodynamic process.

  20. Therapeutic potential of Panax ginseng and ginsenosides in the treatment of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Shergis, J L; Di, Y M; Zhang, A L; Vlahos, R; Helliwell, R; Ye, J M; Xue, C C

    2014-10-01

    Chronic obstructive pulmonary disease (COPD) is a major global health burden and will become the third largest cause of death in the world by 2030. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, cause progressive airflow limitation. This inflammation, where macrophages, neutrophils and lymphocytes are prominent, leads to oxidative stress, emphysema, airways fibrosis and mucus hypersecretion. COPD responds poorly to current anti-inflammatory treatments including corticosteroids, which produce little or no benefit. Panax ginseng has a long history of use in Chinese medicine for respiratory conditions, including asthma and COPD. In this perspective we consider the therapeutic potential of Panax ginseng for the treatment of COPD. Panax ginseng and its compounds, ginsenosides, have reported effects through multiple mechanisms but primarily have anti-inflammatory and anti-oxidative effects. Ginsenosides are functional ligands of glucocorticoid receptors and appear to inhibit kinase phosphorylation including MAPK and ERK1/2, NF-κB transcription factor induction/translocation, and DNA binding. They also inhibit pro-inflammatory mediators, TNF-α, IL-6, IL-8, ROS, and proteases such as MMP-9. Panax ginseng protects against oxidative stress by increasing anti-oxidative enzymes and reducing the production of oxidants. Given that Panax ginseng and ginsenosides appear to inhibit processes related to COPD pathogenesis, they represent an attractive therapeutic target for the treatment of COPD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Biomarkers as Potential Treatment Targets in Inflammatory Bowel Disease: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Travis B Murdoch

    2015-01-01

    Full Text Available There is increasing interest in the concept of ‘treat-to-target’ in inflammatory bowel disease as a mechanism to standardize management and prevent complications. While clinical, radiographic and endoscopic treatment end points will figure prominently in this promising management paradigm, the role that noninvasive biomarkers will play is currently undefined. The goal of the present systematic review was to investigate the potential value of biomarkers as treatment targets in inflammatory bowel disease, with particular focus on those best studied: serum C-reactive protein (CRP and fecal calprotectin. In Crohn disease, elevated CRP levels at baseline predict response to anti-tumour necrosis factor agents, and normalization is usually associated with clinical and endoscopic remission. CRP and hemoglobin levels can be used to help predict clinical relapse in the context of withdrawal of therapy. Ultimately, the authors conclude that currently available biomarkers should not be used as treatment targets in inflammatory bowel disease because they have inadequate operational characteristics to make them safe surrogates for clinical, endoscopic and radiographic evaluation. However, CRP and fecal calprotectin are important adjunctive measures that help alert the clinician to pursue further investigation.

  2. Bariatric surgery and nonalcoholic fatty liver disease: current and potential future treatments

    Directory of Open Access Journals (Sweden)

    Akira eSasaki

    2014-10-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH are increasingly common cause of chronic liver disease worldwide. The diagnosis of NASH is challenging as most affected patients are symptom-free and the role of routine screening is not clearly established. Most patients with severe obesity who undergo bariatric surgery have NAFLD, which is associated insulin resistance, type 2 diabetes mellitus (T2DM, hypertension, and obesity-related dyslipidemia. The effective treatment for NAFLD is weight reduction through lifestyle modifications, antiobesity medication, or bariatric surgery. Among these treatments, bariatric surgery is the most reliable method for achieving substantial, sustained weight loss. This procedure is safe when performed by a skilled surgeon, and the benefits include reduced weight, improved quality of life, decreased obesity-related comorbidities, and increased life expectancy. Further research is urgently needed to determine the best use of bariatric surgery with NAFLD patients at high risk of developing liver cirrhosis and its role in modulating complications of NAFLD, such as T2DM and cardiovascular disease. The current evidence suggests that bariatric surgery for patients with severe obesity decreases the grade of steatosis, hepatic inflammation, and fibrosis. However, further long-term studies are required to confirm the true effects before recommending bariatric surgery as a potential treatment for nonalcoholic steatohepatitis.

  3. Metforminium Decavanadate as a Potential Metallopharmaceutical Drug for the Treatment of Diabetes Mellitus.

    Science.gov (United States)

    Treviño, Samuel; Velázquez-Vázquez, Denisse; Sánchez-Lara, Eduardo; Diaz-Fonseca, Alfonso; Flores-Hernandez, José Ángel; Pérez-Benítez, Aarón; Brambila-Colombres, Eduardo; González-Vergara, Enrique

    2016-01-01

    New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM) and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca), a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatments with 3.7 μg (2.5 μM)/300 g/twice a week for DM2 and 7.18 μg (4.8 μM)/300 g/twice a week for DM1 of MetfDeca, respectively, were administered. The resulting pharmacological data showed nontoxicological effects on liver and kidney. At the same time, MetfDeca showed an improvement of carbohydrates and lipids in tissues and serum. MetfDeca treatment was better than the monotherapies with metformin for DM2 and insulin for DM1. Additionally, MetfDeca showed a protective effect on pancreatic beta cells of DM1 rats, suggesting a possible regeneration of these cells, since they recovered their insulin levels. Therefore, MetfDeca could be considered not only as an insulin-mimetic agent, but also as an insulin-enhancing agent. Efforts to elucidate the mechanism of action of this compound are now in progress.

  4. Potentials of Mangifera indica in the treatment of depressive-anxiety disorders: possible mechanisms of action.

    Science.gov (United States)

    Ishola, Ismail O; Awodele, Olufunsho; Eluogu, Chinedum O

    2016-09-01

    Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic-like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice. HeMI (12.5-100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM). HeMI (12.5-100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, pindica through interaction with 5-HT2 receptor, α2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness.

  5. Sale of fluoroquinolones in northern Tanzania: a potential threat for fluoroquinolone use in tuberculosis treatment.

    Science.gov (United States)

    van den Boogaard, Jossy; Semvua, Hadija H; Boeree, Martin J; Aarnoutse, Rob E; Kibiki, Gibson S

    2010-01-01

    Fluoroquinolones have a potential role in shortening tuberculosis (TB) treatment duration. They are currently used in the treatment of other infections. This has raised concerns about development of mycobacterial resistance. The current study evaluates the sale of fluoroquinolones (among other antibacterials) in Moshi, Tanzania, a country with one of the highest burdens of TB in the world. Trained pharmacy assistants registered the sale of fluoroquinolones during February and March 2009 to outpatients in Moshi in all 14 pharmacies that are authorized to sell antibacterials for systemic use. The sale of all antibacterials of the Anatomical Therapeutic Chemical (ATC) J01 class was expressed in defined daily doses (DDDs) per 1000 inhabitants per day (DID). The availability of fluoroquinolones in drug outlets that are not authorized to sell antibacterials for systemic use was assessed in 15 randomly selected outlets in Moshi. The sale of antibacterials to outpatients in Moshi by authorized pharmacies was 4.99 DID. The sale of fluoroquinolones was 0.62 DID (12% of total antibacterial sales). Ciprofloxacin was available in all 15 unauthorized drug outlets. The substantial sales of fluoroquinolones by authorized pharmacies and the wide availability of fluoroquinolones in unauthorized drug outlets in Moshi constitute a challenge to the use of fluoroquinolones in TB treatment in Tanzania. Control of antibacterial use in Tanzania requires the implementation of surveillance systems for antibacterial use and resistance, and adequate restriction of antibacterial sales to authorized pharmacies only.

  6. Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

    DEFF Research Database (Denmark)

    Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral

    2012-01-01

    The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.......The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF....

  7. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  8. Potential of phosphorus recovery from sewage sludge and manure ash by thermochemical treatment.

    Science.gov (United States)

    Havukainen, Jouni; Nguyen, Mai Thanh; Hermann, Ludwig; Horttanainen, Mika; Mikkilä, Mirja; Deviatkin, Ivan; Linnanen, Lassi

    2016-03-01

    All life forms require phosphorus (P), which has no substitute in food production. The risk of phosphorus loss from soil and limited P rock reserves has led to the development of recycling P from industrial residues. This study investigates the potential of phosphorus recovery from sewage sludge and manure ash by thermochemical treatment (ASH DEC) in Finland. An ASH DEC plant could receive 46-76 kt/a of sewage sludge ash to produce 51-85 kt/a of a P-rich product with a P2O5 content of 13-18%, while 320-750 kt/a of manure ash could be supplied to produce 350-830 kt/a of a P-rich product with a P content of 4-5%. The P2O5 potential in the total P-rich product from the ASH DEC process using sewage sludge and manure ash is estimated to be 25-47 kt/a, which is significantly more than the P fertilizer demand in Finland's agricultural industries. The energy efficiency of integrated incineration and the ASH DEC process is more dependent on the total solid content and the subsequent need for mechanical dewatering and thermal drying than on the energy required by the ASH DEC process. According to the results of this study, the treated sewage sludge and manure ash using the ASH DEC process represent significant potential phosphorus sources for P fertilizer production. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Synthesis, Preliminary Bioevaluation and Computational Analysis of Caffeic Acid Analogues

    Directory of Open Access Journals (Sweden)

    Zhiqian Liu

    2014-05-01

    Full Text Available A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.

  10. Tidal regimes and salt marshes - the River Hamble analogue

    International Nuclear Information System (INIS)

    Gray, A.J.; Moy, I.L.; Warman, E.A.; Dawson, F.H.; Henville, P.

    1993-01-01

    Construction of estuarine tidal-energy barrages has a potentially major effect on the tidal regime of the estuary, particularly upstream of a barrage. Because tidal regime largely controls the distribution and species composition of intertidal plant and animal communities, it is important to understand how barrages may affect such communities. The main objectives of the research described in this report were to relate recent changes in tidal regime within an embanked area of salt marsh and mudflat to changes in the distribution of plant species. This was to test predictions about tidal control of species' range and to assess the site's suitability as an analogue of post-barrage conditions. (author)

  11. Partial MHC/neuroantigen peptide constructs: a potential neuroimmune-based treatment for methamphetamine addiction.

    Directory of Open Access Journals (Sweden)

    Jennifer M Loftis

    Full Text Available Relapse rates following current methamphetamine abuse treatments are very high (∼40-60%, and the neuropsychiatric impairments (e.g., cognitive deficits, mood disorders that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-A(b/mMOG-35-55, in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.. Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2 levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments.

  12. Chitosan and glyceryl monooleate nanostructures containing gemcitabine: potential delivery system for pancreatic cancer treatment.

    Science.gov (United States)

    Trickler, William J; Khurana, Jatin; Nagvekar, Ankita A; Dash, Alekha K

    2010-03-01

    The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures, and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size, and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular internalization and cytotoxicity of the nanostructures were evaluated by HPLC, confocal microscopy, or MTT assay in Mia PaCa-2 and BxPC-3 cells. The average particle diameter for 2% and 4% (w/w) drug loaded delivery system were 382.3 +/- 28.6 nm, and 385.2 +/- 16.1 nm, respectively with a surface charge of +21.94 +/- 4.37 and +21.23 +/- 1.46 mV. The MTT cytotoxicity dose-response studies revealed the placebo at/or below 1 mg/ml has no effect on MIA PaCa-2 or BxPC-3 cells. The delivery system demonstrated a significant decrease in the IC50 (3 to 4 log unit shift) in cell survival for gemcitabine nanostructures at 72 and 96 h post-treatment when compared with a solution of gemcitabine alone. The nanostructure reported here can be resuspended in an aqueous medium that demonstrate increased effective treatment compared with gemcitabine treatment alone in an in vitro model of human pancreatic cancer. The drug delivery system demonstrates capability to entrap both hydrophilic and hydrophobic compounds to potentially provide an effective treatment option in human pancreatic cancer.

  13. Evidence-based dentistry for planning restorative treatments: barriers and potential solutions.

    Science.gov (United States)

    Afrashtehfar, K I; Eimar, H; Yassine, R; Abi-Nader, S; Tamimi, F

    2017-11-01

    Evidence-based dentistry (EBD) can help provide the best treatment option for every patient, however, its implementation in restorative dentistry is very limited. This study aimed at assessing the barriers preventing the implementation of EBD among dental undergraduate and graduate students in Montreal, and explore possible solutions to overcome these barriers. A cross-sectional survey was conducted by means of a paper format self-administrated questionnaire distributed among dental students. The survey assessed the barriers and potential solutions for implementation of an evidence-based practice. Sixty-one students completed the questionnaire. Forty-one percent of respondents found evidence-based literature to be the most reliable source of information for restorative treatment planning, however, only 16% used it. They considered that finding reliable information was difficult and they sometimes encountered conflicting information when consulting different sources. Dental students had positive attitudes towards the need for better access to evidence-based literature to assist learning and decision making in restorative treatment planning and to improve treatment outcomes. Even for dentists trained in EBD, online searching takes too much time, and even though it can provide information of better quality than personal intuition, it might not be enough to identify the best available evidence. Even though dental students are aware of the importance of EBD in restorative dentistry they rarely apply the concept, mainly due to time constraints. For this reason, implementation of EBD would probably require faster access to evidence-based knowledge. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Partial MHC/Neuroantigen Peptide Constructs: A Potential Neuroimmune-Based Treatment for Methamphetamine Addiction

    Science.gov (United States)

    Loftis, Jennifer M.; Wilhelm, Clare J.; Vandenbark, Arthur A.; Huckans, Marilyn

    2013-01-01

    Relapse rates following current methamphetamine abuse treatments are very high (∼40–60%), and the neuropsychiatric impairments (e.g., cognitive deficits, mood disorders) that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-Ab/mMOG-35-55), in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.). Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2) levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments. PMID:23460798

  15. Ho-166 Hydroxyapatite (Ha) as a potential therapeutic agent in the treatment of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Chandia, M.; Errazu, X.; Pinto, L.; Troncoso, F.; Mendoza, P.; Jofre, J.

    2004-01-01

    Radiation synovectomy is a procedure which is aimed at ablation of the inflamed synovium in rheumatoid arthritis through intraarticular injection of a chemical substance labeled with a beta-emitting radioisotope. The objective of this study was to evaluate Ho-166 Hydoxyapatite (Ho-166 HA) particle as potential therapeutic agent for the treatment of acute and chronic arthritis. Ho-166 was obtained by irradiation of 165 Ho 2 O 3 in the 5 MW Research Reactors (RECH1) at the Nuclear Centre La Reina (Chilean Nuclear Energy Commission). The HA synthesis, Ho-166 HA labeling and quality control procedures were performed in the laboratories of Chilean Atomic Energy Commission. Two groups of arthritic (acute and chronic) rabbits with antigen-induced arthritis were administered Ho-166 HA intra-articularly following two different protocols; single dose protocol and double dose protocol. The therapeutic efficacy of Ho-166 HA was assessed by clinical follow-up and evaluation, as well as by serial radionuclide imaging of the inflamed joints with Ga-67 Citrate, before and after treatment. The average radionuclide purity of administered Ho-166 HA in our study was 99%. All animals were followed up by clinical examination. Grades of inflammation, general physical conditions as well as the level of appetite were recorded following treatment. The localization and distribution of the Ho-166 HA were studied by gamma camera imaging at 4 and 24 hrs after-injections. The scans were examined meticulously to look for any evidence of leakage of radiopharmaceutical from the joint space. The group of animals with acute arthritis showed evidence of significant clinical improvement following radionuclide therapy. The animals which received higher doses (double dose) demonstrated better therapeutic response. Based on the preliminary reports from this pilot study it was concluded that Ho-166 HA is a useful radiopharmaceutical for the treatment of rheumatoid arthritis. (author)

  16. Unresectable Recurrent Multiple Meningioma: A Case Report with Radiological Response to Somatostatin Analogues

    Directory of Open Access Journals (Sweden)

    Ana Ortolá Buigues

    2016-08-01

    Full Text Available Medical treatment of meningiomas is reserved for cases in which surgery and radiotherapy have failed. Given that a high percentage of meningiomas express somatostatin receptors, treatment with somatostatin analogues has been proposed. In addition, these medications have been shown to have an antiproliferative and antiangiogenic effect in vitro. To date, very few cases with clinical response and none with radiological response have been described. The case described here is the first to report a radiological response. A 76-year-old Caucasian male was first diagnosed with unresectable meningioma at age 47. The patient experienced multiple recurrences and underwent three surgeries and radiotherapy over the years from the initial diagnosis. Despite treatment, the disease continued its progression. Based on an Octreoscan positive for tumour uptake, therapy with extended-release somatostatin analogues was started. Although no clinical neurological improvement was observed, magnetic resonance imaging scans revealed a discreet but continuous radiological response over time. After >2 years of continuous administration of lanreotide, the patient remains progression free. In highly selected cases, somatostatin analogue treatment for meningioma may be beneficial. Based on our findings, treatment with somatostatin analogues should be maintained longer than previously described before evaluating treatment response.

  17. Ozonation and thermal pre-treatment of municipal sewage sludge – Implications for toxicity and methane potential

    DEFF Research Database (Denmark)

    Davidsson, A.; Eriksson, Eva; Fick, J.

    The aim of this study was to determine the effects on the methane potential and the overall sludge quality from two different sludge pre-treatment technologies (ozonation high/low dosage and thermal treatment 55/70 °C). In general both treatments gave an increased methane potential. The thermal...... treatment resulted in higher chemical oxygen demand (COD)-solubilisation, while the highest volatile fatty acids (VFA) increase was obtained with ozonation. The sludges had inhibiting effects in a barley seed germination assay and a yeast oestrogen screen both before and after pre...

  18. Separation, Characterization and Fouling Potential of Sludge Waters from Different Biological Wastewater Treatment Processes

    KAUST Repository

    Xue, Jinkai

    2011-07-01

    The major limitation, which hinders the wider application of membrane technology and increases the operating costs of membranes involved in wastewater treatment plants, is membrane fouling induced by organic matter. Extracellular polymeric products (EPS) and soluble microbial products (SMP) are the two most mentioned major foulants in publications, for which the debate on precise definitions seems to be endless. Therefore, a concept of sludge water, which conceptually covers both EPS and SMP, has been developed in this research. A standard procedure of sludge water separation, which is centrifugation at 4000g for 15 min followed by 1.2μm glass fiber filter filtration, was established based on separation experiments with membrane tank sludge from the KAUST MBR wastewater treatment plant. Afterwards, sludge waters from the KAUST MBR WWTP anoxic tank, aerobic tank and membrane tank as well as sludge waters from the Jeddah WWTP anoxic tank, aerobic tank and secondary effluent were produced through the previously developed standard procedure. The obtained sludge water samples were thereafter characterized with TOC/COD, LC-­‐OCD and F-­‐EEM, which showed that KAUST anoxic/ aerobic /membrane tank sludge waters had similar characteristics for all investigated parameters, yet the influent naturally had a higher DOC and biopolymer concentration. Moreover, lower TOC/COD, negligible biopolymers and low levels of humics were found in KAUST effluent. Compared with the KAUST MBR WWTP, the Jeddah WWTP’s sludge waters generally had higher DOC and biopolymer concentrations. To investigate sludge water fouling potential, the KAUST membrane tank sludge water as well as the Jeddah secondary effluent were filtrated through a membrane array consisting of an ultrafiltration (UF) Millipore RC10kDa at the first step followed by a nanofiltration (NF) KOCH Acid/Base stable NF200 at the second step. It was found that cake layer and standard blocking occurred simultaneously during both

  19. Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats

    Science.gov (United States)

    Chen, Yen-Cheng; Ho, Ching-Chun; Yi, Chih-Hsun; Liu, Xiu-Zhu; Cheng, Tzu-Ting

    2017-01-01

    Background Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats. Methods and results Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area. Conclusion Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes. PMID:29095895

  20. Analogue alternative the electronic analogue computer in Britain and the USA, 1930-1975

    CERN Document Server

    Small, James S

    2013-01-01

    We are in the midst of a digital revolution - until recently, the majority of appliances used in everyday life have been developed with analogue technology. Now, either at home or out and about, we are surrounded by digital technology such as digital 'film', audio systems, computers and telephones. From the late 1940s until the 1970s, analogue technology was a genuine alternative to digital, and the two competing technologies ran parallel with each other. During this period, a community of engineers, scientists, academics and businessmen continued to develop and promote the analogue computer.

  1. Selamectin Is the Avermectin with the Best Potential for Buruli Ulcer Treatment.

    Directory of Open Access Journals (Sweden)

    Nicole Scherr

    2015-08-01

    Full Text Available A comprehensive analysis was done to evaluate the potential use of anti-parasitic macrocyclic lactones (including avermectins and milbemycins for Buruli ulcer (BU therapy. A panel containing nearly all macrocyclic lactones used in human or in veterinary medicine was analyzed for activity in vitro against clinical isolates of Mycobacterium ulcerans. Milbemycin oxime and selamectin were the most active drugs against M. ulcerans with MIC values from 2 to 8 μg/mL and 2 to 4 μg/mL, respectively. In contrast, ivermectin and moxidectin, which are both in clinical use, showed no significant activity (MIC> 32 μg/mL. Time-kill kinetic assays showed bactericidal activity of selamectin and in vitro pharmacodynamic studies demonstrated exposure-dependent activity. These data together with analyses of published pharmacokinetic information strongly suggest that selamectin is the most promising macrocyclic lactone for BU treatment.

  2. The potential role of vitamin D for prevention and treatment of tuberculosis and infectious diseases.

    Science.gov (United States)

    Dini, Catia; Bianchi, Antonio

    2012-01-01

    Vitamin D deficiency (VDD) is a common condition among several populations in the world. VDD is associated with higher incidence of immune system disorders and faster progression of some infectious diseases. Vitamin D is known to be of physiological importance, it is considered an essential micronutrient for the bone health and plays a beneficial role in the prevention and/or treatment of a number of chronic diseases. Vitamin D has a complex action on the immune system. Evidence that vitamin D protects against tuberculosis has been supported by in vitro, epidemiological and some preliminary clinical studies. Vitamin D has a potential effect on HIV (human immunodeficiency virus) and plays a crucial role in the defence against respiratory infections. Vitamin D supplementation could be a low-cost, practical method to protect groups of people with high incidence of those diseases. Public health education should stress the need for adequate dietary intake of vitamin D in those vulnerable groups.

  3. Microtubule Stabilizing Agents as Potential Treatment for Alzheimer’s Disease and Related Neurodegenerative Tauopathies

    Science.gov (United States)

    Ballatore, Carlo; Brunden, Kurt R.; Huryn, Donna M.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Smith, Amos B.

    2012-01-01

    The microtubule (MT)-associated protein tau, which is highly expressed in the axons of neurons, is an endogenous MT-stabilizing agent that plays an important role in the axonal transport. Loss of MT-stabilizing tau function, caused by misfolding, hyperphosphorylation and sequestration of tau into insoluble aggregates, leads to axonal transport deficits with neuropathological consequences. Several in vitro and preclinical in vivo studies have shown that MT-stabilizing drugs can be utilized to compensate for the loss of tau function and to maintain/restore an effective axonal transport. These findings indicate that MT-stabilizing compounds hold considerable promise for the treatment of Alzheimer disease and related tauopathies. The present article provides a synopsis of the key findings demonstrating the therapeutic potential of MT-stabilizing drugs in the context of neurodegenerative tauopathies, as well as an overview of the different classes of MT-stabilizing compounds. PMID:23020671

  4. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

    Science.gov (United States)

    Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

    2013-01-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

  5. Histone deacetylase inhibitors as potential therapeutic agents for the treatment of malignant mesothelioma.

    Science.gov (United States)

    Katafygiotis, Patroklos; Giaginis, Constantinos; Patsouris, Efstratios; Theocharis, Stamatios

    2013-03-01

    Histone deacetylase inhibitors (HDACIs) represent one of the most promising, recently developed classes of anticancer agents already approved by the U.S. FDA. The effectiveness of these new drugs has currently being explored in a variety of cancer cell lines, in vitro, animal models, in vivo, as well as in clinical trials. Malignant mesothelioma (MM) is a rare aggressive malignancy with a median overall survival of 12 months when the current chemotherapy regimen, cisplatin-pemetrexed, is applied. This disappointing overall survival has encouraged the experimental use of novel pharmaceutical agents, including HDACIs. In this aspect, the present review is aimed to summarize the existing data regarding the potential utility of HDACIs as therapeutic targets for the treatment of MM. Taking into consideration the research investigations so far, both in vitro and in vivo studies have documented encouraging results. Promising results are also being expected by ongoing clinical trials that concern combination of chemotherapy with HDACIs against MM.

  6. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  7. Renal denervation using focused infrared fiber lasers: a potential treatment for hypertension.

    Science.gov (United States)

    Alexander, Vinay V; Shi, Zhennan; Iftekher, Fariha; Welsh, Michael J; Gurm, Hitinder S; Rising, Gail; Yanovich, Amber; Walacavage, Kim; Islam, Mohammed N

    2014-11-01

    Renal denervation has recently become of great interest as a potential treatment for resistant hypertension. Denervation techniques using radio frequency (RF) or ultrasound energy sources have already been explored in literature. In this study, we investigate the use of lasers as a potential energy source for renal denervation. In vitro studies are performed in porcine/ovine renal arteries with focused laser beams at 980 nm, 1210 nm, and 1700 nm to study the ability to damage renal nerves without causing injury to non-target tissue structures like the endothelium. Then, a 980 nm laser catheter prototype is built and used to demonstrate in vivo renal denervation in ovine renal arteries. This study utilizes fiber coupled infrared lasers at 980 nm, 1210 nm, and 1700 nm. In vitro laser denervation studies at 980 nm are performed in both porcine and ovine renal arteries to study the ability of focused laser beams to damage renal nerves without injuring the endothelium. In vitro studies using lasers close to the lipid absorption lines at 1210 nm and 1700 nm are also performed in porcine renal arteries to study the possibility of selectively damaging the renal nerves by targeting the lipid myelin sheaths surrounding the nerves. Then, a laser catheter prototype is designed and built for in vivo renal denervation in ovine renal arteries using the 980 nm laser (powers ranging from 2 to 4 W, 5 seconds per exposure). Histochemical evaluations of the frozen sections are performed using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Histochemical analysis of in vitro laser treatments at 980 nm in porcine and ovine renal arteries show clear evidence of laser-induced renal nerve damage without injury to the endothelium and part of the media. No evidence of selective nerve damage is observed using the 1210 nm and 1700 nm lasers with the current treatment parameters. Histochemical analysis of in vivo laser treatments in ovine renal arteries

  8. Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

    Energy Technology Data Exchange (ETDEWEB)

    Beane, Olivia S. [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Fonseca, Vera C. [Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Darling, Eric M., E-mail: Eric_Darling@brown.edu [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Department of Orthopaedics, Brown University, Providence, RI (United States); School of Engineering, Brown University, Providence, RI (United States)

    2014-10-01

    In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

  9. The potential of quinoline derivatives for the treatment of Toxoplasma gondii infection.

    Science.gov (United States)

    Kadri, Dema; Crater, Anna K; Lee, Hoyun; Solomon, V Raja; Ananvoranich, Sirinart

    2014-10-01

    Here we reported our investigation, as part of our drug repositioning effort, on anti-Toxoplasma properties of newly synthesized quinoline compounds. A collection of 4-aminoquinoline and 4-piperazinylquinoline analogs have recently been synthesized for use in cancer chemotherapy. Some analogs were able to outperform chloroquine, a quinoline derivative drug which is commonly used in the treatment of malaria and other parasitic infections. Herein 58 compounds containing one or two quinoline rings were examined for their effectiveness as potential anti-Toxoplasma compounds. Of these 58 compounds, 32 were efficient at inhibiting Toxoplasma growth (IC50Toxoplasma effect among quinoline derivatives was detected in B11, B12, B23, and B24, whose structures carry two quinoline rings, and their resultant cLogP values are ⩾7. Among these compounds, B23 was the most effective compound with IC50 value of 425±35 nM, and TI value of 4.9. It was also noted that compounds with at least one quinoline ring, displaying anti-Toxoplasma effects were capable of causing the disappearance of the apicoplast, a plastid-like organelle. When treated with quinoline, 8-hydroxyquinoline or B23, 40-45% of the parasites lost their apicoplasts. Our findings recapitulate the properties of quinoline derivatives in diminishing apicoplast. This could aid further investigations of anti-parasitic treatments specific to Apicomplexan. More importantly, B12 and B23 which harbor superior anti-cancer properties than chloroquine, have effective anti-Toxoplasma activity. These compounds therefore have significant potential for future development of chemotherapeutic agents for patients suffering from breast cancers and parasitic infection. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin.

    Science.gov (United States)

    Saleh, Mohammad I; Nalbant, Demet; Widness, John A; Veng-Pedersen, Peter

    2013-05-01

    A population pharmacokinetics/pharmacodynamic (PK/PD) model was developed to describe changes in erythropoiesis as a function of plasma erythropoietin (EPO) concentration over the first 30 days of life in preterm infants who developed severe anemia requiring red blood cell (RBC) transfusion. Several covariates were tested as possible factors influencing the responsiveness to EPO. Discarded blood samples in 27 ventilated preterm infants born at 24-29 wk of gestation were used to construct plasma EPO, hemoglobin (Hb), and RBC concentration-time profiles. The amount of Hb removed for laboratory testing and that transfused throughout the study period were recorded. A population PK/PD model accounting for the dynamic Hb changes experienced by these infants was simultaneously fitted to plasma EPO, Hb, and RBC concentrations. A covariate analysis suggested that the erythropoietic efficacy of EPO is increased for preterm infants at later gestational ages. The PD analysis showed a sevenfold difference in maximum Hb production rate dependent on gestational age and indicated that preterm infants, when stimulated by EPO, have the capacity to produce additional Hb that may result in a decrease in RBC transfusions. The present model has utility in clinical trial simulations investigating the treatment potential of erythropoietic stimulating agents in the treatment of anemia of prematurity.

  11. Development of alpha-emitting radionuclide lead 212 for the potential treatment of ovarian carcinoma

    International Nuclear Information System (INIS)

    Rotmensch, J.; Atcher, R.W.; Hines, J.; Grdina, D.; Schwartz, J.S.; Toohill, M.; Herbst, A.L.

    1989-01-01

    alpha-Emitting radionuclides may be an effective alternative treatment against ovarian carcinoma because they have short half-lives and are densely ionizing, with high linear energy transfer to a depth of several cell diameters without requiring cellular oxygenation. One radionuclide that has been generated and tested in our laboratory in vitro and in vivo is lead 212 ( 212 Pb). Intraperitoneal instillation of 212 Pb prolonged survival and totally eradicated tumor in 24% of mice inoculated with the extremely virulent Ehrlich ascites-producing tumor. In vitro 212 Pb was two to four times more effective in killing human ovarian cancer cells than x-rays. Irradiation with 212 Pb increased the radiosensitivity and chromosomal aberrations of cells. In dogs, intraperitoneal instillation of 2.6 mCi of ferrous hydroxide tagged with 212 Pb caused no significant toxicity. It appears that alpha-emitting radionucides such as 212 Pb have the potential to be a new and potent treatment of ovarian carcinoma and could be effective in cases that are resistant to conventional chemotherapy or x-ray therapy

  12. Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

    Science.gov (United States)

    Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

    2014-01-01

    To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

  13. Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

    Directory of Open Access Journals (Sweden)

    Felix Grases

    Full Text Available To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis.The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM. The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL was evaluated using a flow system.The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments.Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

  14. Bone marrow mononuclear stem cells: potential in the treatment of myocardial infarction

    Directory of Open Access Journals (Sweden)

    Anne-Laure Leblond

    2009-12-01

    Full Text Available Anne-Laure Leblond, John O’Sullivan, Noel Caplice1Centre for Research in Vascular Biology (CRVB, Biosciences Institute, University College Cork, Cork, IrelandAbstract: Despite advances in the management of myocardial infarction, congestive heart failure following myocardial infarction continues to be a major worldwide medical problem. Mononuclear cells from bone marrow are currently being studied as potential candidates for cellbased therapy to repair and regenerate damaged myocardium, with mixed results. The success of this strategy requires structural repair through both cardiomyogenesis and angiogenesis but also functional repair. However, pre-clinical and clinical studies with the intracoronary administration of cells indicate limited cardiomyogenesis and cell survival, controversial functional benefit and suggest paracrine effects mediated by the administered cells. Further investigations for optimizing therapeutic benefit focus on the requirement for stable cell engraftment and the involvement of cytokines in this process. This includes a large and varied range of strategies including cell or heart pre-treatment, tissue engineering and protein therapy. Although cellbased therapy holds promise in the future treatment of myocardial infarction, its current use is significantly hampered by biological and technological challenges.Keywords: bone marrow mononuclear cells, myocardial infarction, cardiac cell therapy

  15. Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

    Science.gov (United States)

    Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

    2014-01-01

    Purpose To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. Materials and Methods The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. Results The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Conclusions Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis. PMID:25333633

  16. The therapeutic potential of regulatory T cells for the treatment of autoimmune disease.

    Science.gov (United States)

    Bluestone, Jeffrey A; Trotta, Eleonora; Xu, Daqi

    2015-01-01

    Immune tolerance remains the holy grail of therapeutic immunology in the fields of organ and tissue transplant rejection, autoimmune diseases, and allergy and asthma. We have learned that FoxP3(+)CD4(+) regulatory T cells play a vital role in both the induction and maintenance of self-tolerance. In this opinion piece, we highlight regulatory T cells (Treg) cell biology and novel immune treatments to take advantage of these cells as potent therapeutics. We discuss the potential to utilize Treg and Treg-friendly therapies to replace current general immunosuppressives and induce tolerance as a path towards a drug-free existence without associated toxicities. Finally, we opine on the fact that biomedicine sits on the cusp of a new revolution: the use of human cells as versatile therapeutic engines. We highlight the challenges and opportunities associated with the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably regulating cellular behaviors. Although Treg therapy has become a legitimate clinical treatment, development of the therapy will require a better understanding of the underlying Treg biology, manufacturing advances to promote cost effectiveness and combinations with other drugs to alter the pathogenicity/regulatory balance.

  17. Microbiota of Chronic Diabetic Wounds: Ecology, Impact, and Potential for Innovative Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Sónia G. Pereira

    2017-09-01

    Full Text Available World Health Organization considered diabetes as one of the 20th century epidemics, estimating that over 10% of the world population is diabetic or at high risk. Self-assessment studies indicate that diabetic patients consider chronic wounds to affect their quality of life more dramatically than vision loss or renal failure. In addition to being the main reason for diabetic patients’ hospitalization, the economic burden of diabetic chronic wounds is close to 1% of United Kingdom and United States health systems budgets, which exceeds the funds allocated to the treatment of some types of cancer in both countries. Among the factors preceding the emergence of chronic diabetic wounds, also designated diabetic foot ulcers (DFUs, hygiene and pressure in specific areas are under patient control, while others are still far from being understood. A triple impairment in the innervation, immune responses, and vascularization associated to DFU has been extensively studied by the scientific community. However, the skin natural microbiota has only recently emerged as having a tremendous impact on DFU emergence and evolution to chronicity. Despite the great inter- and intra-variability of microbial colonizers, ongoing efforts are now focused on deciphering the impact of commensal and pathogenic microbiota on DFU etiology, as well as the mechanisms of interkingdom microbial–host communication. This review summarizes recent work in this context and offers new microbiological perspectives that may hold potential in the prevention and treatment of chronic diabetic wounds.

  18. POTENTIAL OF MULTI-TEMPORAL UAV-BORNE LIDAR IN ASSESSING EFFECTIVENESS OF SILVICULTURAL TREATMENTS

    Directory of Open Access Journals (Sweden)

    U. Vepakomma

    2017-08-01

    Full Text Available Silvicultural treatments are practiced to control resource competition and direct forest stand development to meet management objectives. Effective tracking of thinning and partial cutting treatments help in timely mitigation and ensuring future stand productivity. Based on a study conducted in autumn 2015, our findings in a white pine dominant forest stand in Petawawa (Ontario, Canada showed that almost all individual trees were detectable, structure of individual trees and undergrowth was well pronounced and underlying terrain below dense undisturbed canopy was well captured with UAS based Riegl Vux-1 lidar even at a range of 150 m. Thereafter, the site was re-scanned the following summer with the same system. Besides understanding the difference in distribution patterns due to foliage conditions, co-registering the two datasets, in the current study, we tested the potential of quantifying effectiveness of a partial cutting silvicultural system especially in terms of filling of 3D spaces through vertical or lateral growth and mortality in a very short period of time.

  19. The potential role of atypical antipsychotics in the treatment of panic disorder.

    Science.gov (United States)

    Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

    2014-09-01

    Many studies have investigated the efficacy and tolerability of alternative pharmacotherapy for panic disorder. This study aims to provide a comprehensive review of the existing literature regarding the efficacy and tolerability of atypical antipsychotics for panic disorder. We searched for relevant published articles using Medline, the Cochrane database, and EMBASE on 19 June 2013. Prospective studies that examined the efficacy and tolerability of atypical antipsychotics in the treatment of primary panic disorder or comorbid panic disorder (or symptoms) in other psychiatric disorders were included in this review. Seven prospective studies were included in this review. Among these, four were open-label studies for refractory panic disorder. Two of the seven included studies were randomized controlled trials among patients with panic symptoms comorbid with bipolar disorder. The remaining study was a randomized controlled trial for panic disorder or panic attack comorbid with major depression. Except one negative risperidone study, the reviewed studies showed the favorable efficacy results of atypical antipsychotics. Although the majority of the evidence regarding the efficacy of atypical antipsychotics in the treatment of panic disorder comes from small, open-label studies, this review suggests the potential role of atypical antipsychotics in treating panic disorder. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Advanced biomaterials and their potential applications in the treatment of periodontal disease.

    Science.gov (United States)

    Chen, Xi; Wu, Guofeng; Feng, Zhihong; Dong, Yan; Zhou, Wei; Li, Bei; Bai, Shizhu; Zhao, Yimin

    2016-08-01

    Periodontal disease is considered as a widespread infectious disease and the most common cause of tooth loss in adults. Attempts for developing periodontal disease treatment strategies, including drug delivery and regeneration approaches, provide a useful experimental model for the evaluation of future periodontal therapies. Recently, emerging advanced biomaterials including hydrogels, films, micro/nanofibers and particles, hold great potential to be utilized as cell/drug carriers for local drug delivery and biomimetic scaffolds for future regeneration therapies. In this review, first, we describe the pathogenesis of periodontal disease, including plaque formation, immune response and inflammatory reactions caused by bacteria. Second, periodontal therapy and an overview of current biomaterials in periodontal regenerative medicine have been discussed. Third, the roles of state-of-the-art biomaterials, including hydrogels, films, micro/nanofibers and micro/nanoparticles, developed for periodontal disease treatment and periodontal tissue regeneration, and their fabrication methods, have been presented. Finally, biological properties, including biocompatibility, biodegradability and immunogenicity of the biomaterials, together with their current applications strategies are given. Conclusive remarks and future perspectives for such advanced biomaterials are discussed.

  1. Potential of Multi-Temporal Uav-Borne LIDAR in Assessing Effectiveness of Silvicultural Treatments

    Science.gov (United States)

    Vepakomma, U.; Cormier, D.

    2017-08-01

    Silvicultural treatments are practiced to control resource competition and direct forest stand development to meet management objectives. Effective tracking of thinning and partial cutting treatments help in timely mitigation and ensuring future stand productivity. Based on a study conducted in autumn 2015, our findings in a white pine dominant forest stand in Petawawa (Ontario, Canada) showed that almost all individual trees were detectable, structure of individual trees and undergrowth was well pronounced and underlying terrain below dense undisturbed canopy was well captured with UAS based Riegl Vux-1 lidar even at a range of 150 m. Thereafter, the site was re-scanned the following summer with the same system. Besides understanding the difference in distribution patterns due to foliage conditions, co-registering the two datasets, in the current study, we tested the potential of quantifying effectiveness of a partial cutting silvicultural system especially in terms of filling of 3D spaces through vertical or lateral growth and mortality in a very short period of time.

  2. Clinical Outcome Following Oral Potentially Malignant Disorder Treatment: A 100 Patient Cohort Study

    Directory of Open Access Journals (Sweden)

    A. Diajil

    2013-01-01

    Full Text Available Oral potentially malignant disorders (PMDs are at risk of transforming to invasive squamous cell carcinoma (SCC, but controversy exists over their management and the precise role of interventional treatment. In this study, a cohort of 100 patients presenting with new, single oral dysplastic PMD lesions were followed for up to 10 years following laser excision. PMDs presented primarily as homogeneous leukoplakias on floor of mouth and ventrolateral tongue sites and showed mainly high-grade dysplasia following analysis of excision specimens. Sixty-two patients were disease-free at the time of the most recent followup, whilst 17 experienced same site PMD recurrence, 14 developed further PMDs at new sites, 5 underwent same site malignant transformation, and 2 developed SCC at new oral sites. Whilst laser excision is an effective therapeutic tool in PMD management, prolonged patient followup and active mucosal surveillance together with clear definitions of clinical outcomes are all essential prerequisites for successful interventional management. Multicentre, prospective, and randomised trials of PMD treatment intervention are urgently required to determine optimal management strategies.

  3. Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma.

    Science.gov (United States)

    Wu, Chun-Chieh; Lin, Zu-Yau; Kuoc, Chao-Hung; Chuang, Wan-Long

    2015-05-01

    Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH) were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment). Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p colchicine-treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167). The tumor growth rates in colchicine-treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015). In addition to the well-known direct colchicine-tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase-polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT-COI. There was no effect of colchicine on MT-COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long-standing prescription experience. Copyright © 2015. Published by Elsevier Taiwan.

  4. Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.

    Science.gov (United States)

    González-Vázquez, Patricia; Larrañeta, Eneko; McCrudden, Maelíosa T C; Jarrahian, Courtney; Rein-Weston, Annie; Quintanar-Solares, Manjari; Zehrung, Darin; McCarthy, Helen; Courtenay, Aaron J; Donnelly, Ryan F

    2017-11-10

    Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Dissolved effluent organic matter: Characteristics and potential implications in wastewater treatment and reuse applications.

    Science.gov (United States)

    Michael-Kordatou, I; Michael, C; Duan, X; He, X; Dionysiou, D D; Mills, M A; Fatta-Kassinos, D

    2015-06-15

    Wastewater reuse is currently considered globally as the most critical element of sustainable water management. The dissolved effluent organic matter (dEfOM) present in biologically treated urban wastewater, consists of a heterogeneous mixture of refractory organic compounds with diverse structures and varying origin, including dissolved natural organic matter, soluble microbial products, endocrine disrupting compounds, pharmaceuticals and personal care products residues, disinfection by-products, metabolites/transformation products and others, which can reach the aquatic environment through discharge and reuse applications. dEfOM constitutes the major fraction of the effluent organic matter (EfOM) and due to its chemical complexity, it is necessary to utilize a battery of complementary techniques to adequately describe its structural and functional character. dEfOM has been shown to exhibit contrasting effects towards various aquatic organisms. It decreases metal uptake, thus potentially reducing their bioavailability to exposed organisms. On the other hand, dEfOM can be adsorbed on cell membranes inducing toxic effects. This review paper evaluates the performance of various advanced treatment processes (i.e., membrane filtration and separation processes, activated carbon adsorption, ion-exchange resin process, and advanced chemical oxidation processes) in removing dEfOM from wastewater effluents. In general, the literature findings reveal that dEfOM removal by advanced treatment processes depends on the type and the amount of organic compounds present in the aqueous matrix, as well as the operational parameters and the removal mechanisms taking place during the application of each treatment technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Metforminium Decavanadate as a Potential Metallopharmaceutical Drug for the Treatment of Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Samuel Treviño

    2016-01-01

    Full Text Available New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca, a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatments with 3.7 μg (2.5 μM/300 g/twice a week for DM2 and 7.18 μg (4.8 μM/300 g/twice a week for DM1 of MetfDeca, respectively, were administered. The resulting pharmacological data showed nontoxicological effects on liver and kidney. At the same time, MetfDeca showed an improvement of carbohydrates and lipids in tissues and serum. MetfDeca treatment was better than the monotherapies with metformin for DM2 and insulin for DM1. Additionally, MetfDeca showed a protective effect on pancreatic beta cells of DM1 rats, suggesting a possible regeneration of these cells, since they recovered their insulin levels. Therefore, MetfDeca could be considered not only as an insulin-mimetic agent, but also as an insulin-enhancing agent. Efforts to elucidate the mechanism of action of this compound are now in progress.

  7. Total synthesis of sannanine and analogues thereof

    Indian Academy of Sciences (India)

    BADHER NAVEEN

    2018-03-02

    Mar 2, 2018 ... concise manner. The key strategies involve Friedländer quinoline synthesis, demethylation, in situ oxidation and amination process. ..... (b) Hargreaves R, David C L, Whitesell L and Skibo E. B 2003 Design of Quinolinedione-Based Geldanamycin. Analogues Bioorg. Med. Chem. Lett. 13 3075; (c) Arg-.

  8. Ultrasound exfoliation of inorganic analogues of graphene

    Czech Academy of Sciences Publication Activity Database

    Štengl, Václav; Henych, Jiří; Slušná, Michaela; Ecorchard, Petra

    2014-01-01

    Roč. 9, APR (2014), s. 1-14 ISSN 1556-276X R&D Projects: GA ČR(CZ) GA14-05146S Institutional support: RVO:61388980 Keywords : Ultrasound * Exfoliation * Graphene inorganic analogues Subject RIV: CA - Inorganic Chemistry Impact factor: 2.779, year: 2014

  9. The World Is either Digital or Analogue

    NARCIS (Netherlands)

    Berto, F.; Tagliabue, J.

    2014-01-01

    We address an argument by Floridi (Synthese 168(1):151-178, 2009; 2011a), to the effect that digital and analogue are not features of reality, only of modes of presentation of reality. One can therefore have an informational ontology, like Floridi’s Informational Structural Realism, without

  10. Somatostatin analogue scintigraphy and tuberculosis: case report

    International Nuclear Information System (INIS)

    Biancheri, I.; Rudenko, B.; Vautrin, P.; Raddoul, J.; Lamfichek, N.; Kantelip, B.; Mantion, G.

    2005-01-01

    Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

  11. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While

  12. The Palmottu analogue project: overview for 1993

    International Nuclear Information System (INIS)

    Ruskeeniemi, T.; Blomqvist, R.; Suksi, J.; Niini, H.

    1994-01-01

    This article gives a summary of the activities carried out within the Palmottu analogue project in 1993. It consists of (1) an introductory part, followed by (2) a geological description of the site, and (3)an up-to-date summary of the results of the project. (orig.) (33 refs., 6 figs.)

  13. Effects of the hydrogen potential and fungicide treatment on Pitaya seed germination

    Directory of Open Access Journals (Sweden)

    Thiago Alberto Ortiz

    2014-11-01

    Full Text Available The objective of the present study was to evaluate pitaya seed germination under different hydrogen potentials, with or without fungicide treatment. A completely randomized design was employed under a 3 x 13 x 2 factorial scheme, corresponding to three pitaya species (white pitaya, pitaya hybrid I, pitaya hybrid II, thirteen hydrogen potentials (3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, and 9.0 and two fungicide conditions (presence and absence, with four replications. The percentage of germination, germination speed index and mean germination time were evaluated. The data were subjected to ANOVA, and the means were compared using the Scott-Knott test (p < 0.05. The pH influenced the germination speed index in white pitaya. The mean germination time was affected by the pH levels for white pitaya and pitaya hybrid II. The fungicide did not increase the germination percentage in the evaluated species.

  14. Potential of tin (IV) chloride for treatment in Alor Pongsu as stabilized landfill leachate

    Science.gov (United States)

    Zainal, Sharifah Farah Fariza Syed; Aziz, Hamidi Abdul

    2017-10-01

    Leachate production from landfilling contributes crucial pollutants to the environment. This study examined the potential of tin (IV) chloride as coagulant that involved charge neutralization and sweep flocculation mechanisms. The negative charge of leachate is neutralized by adding tin (IV) chloride as cationic coagulant which resulted precipitation and swept most of the colloids and dissolved solids that entrapped in the settling as hydrous oxide floc. Parameters such as suspended solid (SS) content, color, and chemical oxygen demand (COD) were analyzed using standard jar test procedures. The best condition was observed at pH 8, with removal efficiencies of 75.99 %, 99.29 % and 98.36 % for COD, SS, and color, respectively. At optimum dosage, tin (IV) chloride successfully removed 98.40 % for color, 99.54 % for SS and 71.53 % for COD. These results indicated the satisfactory performance of tin (IV) chloride. Hence, tin (IV) chloride is a potential coagulant for the treatment of Alor Pongsu Landfill leachate.

  15. Human infective potential of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi in urban wastewater treatment plant effluents

    Science.gov (United States)

    Cryptosporidiosis, giardiasis, and microsporidiosis are important waterborne diseases. In the standard for wastewater treatment plant (WWTP) effluents in China and other countries, fecal coliform is the only microbial indicator, raising concerns about the potential for pathogen t...

  16. Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment.

    Science.gov (United States)

    de Abreu, Letícia Coli Louvisse; Todaro, Valerio; Sathler, Plinio Cunha; da Silva, Luiz Cláudio Rodrigues Pereira; do Carmo, Flávia Almada; Costa, Cleonice Marques; Toma, Helena Keiko; Castro, Helena Carla; Rodrigues, Carlos Rangel; de Sousa, Valeria Pereira; Cabral, Lucio Mendes

    2016-12-01

    The aim of this work was the development and characterization of nisin-loaded nanoparticles and the evaluation of its potential antifungal activity. Candidiasis is a fungal infection caused by Candida sp. considered as one of the major public health problem currently. The discovery of antifungal agents that present a reduced or null resistance of Candida sp. and the development of more efficient drug release mechanisms are necessary for the improvement of candidiasis treatment. Nisin, a bacteriocin commercially available for more than 50 years, exhibits antibacterial action in food products with potential antifungal activity. Among several alternatives used to modulate antifungal activity of bacteriocins, polymeric nanoparticles have received great attention due to an effective drug release control and reduction of therapeutic dose, besides the minimization of adverse effects by the preferential accumulation in specific tissues. The nisin nanoparticles were prepared by double emulsification and solvent evaporation methods. Nanoparticles were characterized by dynamic light scattering, zeta potential, Fourier transform infrared, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Antifungal activity was accessed by pour plate method and cell counting using Candida albicans strains. The in vitro release profile and in vitro permeation studies were performed using dialysis bag method and pig vaginal mucosa in Franz diffusion cell, respectively. The results revealed nisin nanoparticles (300 nm) with spherical shape and high loading efficiency (93.88 ± 3.26%). In vitro test results suggest a promising application of these nanosystems as a prophylactic agent in recurrent vulvovaginal candidiasis and other gynecological diseases.

  17. Promising Potential of Dietary (Poly)Phenolic Compounds in the Prevention and Treatment of Diabetes Mellitus.

    Science.gov (United States)

    Dias, Tania R; Alves, Marco G; Casal, Susana; Oliveira, Pedro F; Silva, Branca M

    2017-01-01

    The incidence of diabetes mellitus (DM) is reaching alarming proportions worldwide, particularly because it is increasingly affecting younger people. This reflects the sedentary lifestyle and inappropriate dietary habits, especially due to the advent of processed foods in modern societies. Thus, unsurprisingly, the first medical recommendation to patients with clinically evident DM is the alteration in their eating behaviour, particularly regarding carbohydrates and total energy intake. Despite individual and cultural preferences, human diet makes available a large amount of phytochemicals with therapeutic potential. Phenolic compounds are the most abundant class of phytochemicals in edible plants, fruits and beverages. These compounds have strong antioxidant and anti-inflammatory activities that have been associated with specific features of their chemical structure. Among others, such properties make them promising antidiabetic agents and several mechanisms of action have already been proposed. Herein, we discuss the recent findings on the potential of dietary phenolic compounds for the prevention and/or treatment of (pre)diabetes, and associated complications. A broad range of studies supports the innate potential of phenolic compounds to protect against DM-associated deleterious effects. Their antidiabetic activity has been demonstrated by: i) regulation of carbohydrate metabolism; ii) improvement of glucose uptake; iii) protection of pancreatic β-cells; iv) enhancement of insulin action and v) regulation of crucial signalling pathways to cell homeostasis. Dietary phenolic compounds constitute an easy, safe and cost-effective way to combat the worrying scenario of DM. The interesting particularities of phenolic compounds reinforce the implementation of a (poly)phenolic-rich nutritional regime, not only for (pre)diabetic patients, but also for non-diabetic people. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Diuretic activity of C-terminal group analogues of the insect kinins in Acheta domesticus.

    Science.gov (United States)

    Nachman, R J; Coast, G M; Holman, G M; Beier, R C

    1995-01-01

    A series of insect kinin analogues, AFFPWG-X, modified at the C-terminal group, were evaluated in a cricket Malpighian tubule secretion bioassay. The results were compared with activity profiles observed in a cockroach hindgut myotropic bioassay for these analogues. Although the replacement of the C-terminal amide group with a negatively charged acid leads to a precipitious drop in diuretic activity, it can be partially restored with the introduction of ester groups such as methyl or benzyl. The presence of branched chain character in the C-terminal group or a C-terminal alpha-carbon-amide distance spanning five methylene group spacers is incompatible with the receptor interaction required for biological activity. Significant diuretic activity is retained with four or fewer methylene groups in this region. C-terminal group analogues containing -SCH3, -NHCH2CH2OCH3, or -OCH2(C6H5) offered the greatest retention of diuretic activity while providing increased hydrophobicity and/or steric bulk. The data are of potential value in the development of mimetic analogues of this insect neuropeptide family. Mimetic analogues are potentially valuable tools to insect neuroendocrinologists studying diuresis and/or engaged in the development of future pest management strategies.

  19. Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma.

    Science.gov (United States)

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Maatouk, Mouna; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species

  20. Quinine conjugates and quinine analogues as potential antimalarial agents.

    Science.gov (United States)

    Jones, Rachel A; Panda, Siva S; Hall, C Dennis

    2015-06-05

    Malaria is a tropical disease, prevalent in Southeast Asia and Africa, resulting in over half a million deaths annually; efforts to develop new antimalarial agents are therefore particularly important. Quinine continues to play a role in the fight against malaria, but quinoline derivatives are more widely used. Drugs based on the quinoline scaffold include chloroquine and primaquine, which are able to act against the blood and liver stages of the parasite's life cycle. The purpose of this review is to discuss reported biologically active compounds based on either the quinine or quinoline scaffold that may have enhanced antimalarial activity. The review emphasises hybrid molecules, and covers advances made in the last five years. The review is divided into three sections: modifications to the quinine scaffold, modifications to aminoquinolines and finally metal-containing antimalarial compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

    Directory of Open Access Journals (Sweden)

    Gómez-Outes A

    2013-05-01

    and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin or once-weekly dosing (ie, idraparinux and idrabiotaparinux, as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban. In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies.Keywords: anticoagulants, venous thromboembolism, cancer, dabigatran, apixaban, rivaroxaban

  2. Clinical potential, safety, and tolerability of arbaclofen in the treatment of autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Frye RE

    2014-05-01

    Full Text Available Richard E FryeArkansas Children's Hospital Research Institute, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USAAbstract: Autism spectrum disorder (ASD is a behaviorally defined disorder which has increased in prevalence over the last two decades. Despite decades of research, no effective treatment is currently available. Animal models, as well as other lines of evidence, point to abnormalities in the balance of cortical excitation to inhibition in individuals with ASD, with this imbalance resulting in an overall increase in cortical excitation. To reduce cortical excitatory glutamate pathways, arbaclofen, a selective agonist of the gamma aminobutyric acid receptor type B, has been developed. This article reviews the evidence for this treatment for ASD using a systematic review methodology. Overall, a systematic search of the literature revealed 148 relevant references with the majority of these being review papers or news items that mentioned the potential promise of arbaclofen. Five original studies were identified, four of which used STX209, a form of arbaclofen developed by Seaside Therapeutics, Inc., and one which used R-baclofen. In an animal model, treatment of Fragile X, a genetic disease with ASD features, demonstrated a reversal of behavioral, neurological, and neuropathological features associated with the disease. One double-blind, placebo-controlled study treated children and adults with Fragile X. Results from this study were promising, with signs of improvement in social function, especially in the most severely socially impaired. Two studies, one open-label and one double-blind, placebo-controlled, were conducted in children, adolescents, and young adults with ASD. These studies suggested some improvements in socialization, although the effects were limited and may have been driven by individuals with ASD that were higher-functioning. These studies and others that have used arbaclofen for

  3. A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis.

    Directory of Open Access Journals (Sweden)

    Melissa S Love

    2017-02-01

    years. Clofazimine has a long history of use and has demonstrated a good safety profile for a disease that requires chronic dosing for a period of time ranging 3-36 months. These results, taken with clofazimine's status as an FDA-approved drug with over four decades of use for the treatment of leprosy, support the continued investigation of clofazimine both as a new chemical tool for understanding cryptosporidium biology and a potential new treatment of cryptosporidiosis.

  4. Natural product analogues: towards a blueprint for analogue-focused synthesis.

    Science.gov (United States)

    Bebbington, Magnus W P

    2017-08-14

    For the first time a general overview of approaches to the synthesis of natural product analogues is presented. This reflects a process of evolution of natural product synthesis which has accelerated in the years since the implementation of diversity-oriented synthesis, which has emerged in parallel with collective synthesis, diverted total synthesis and the preparation of truncated natural products optimised for biological activity. A method involving computational assessment for the validation of core-modified natural product analogues is discussed.

  5. Antileishmanial activity of lapachol analogues

    Directory of Open Access Journals (Sweden)

    Nadja MF Lima

    2004-11-01

    Full Text Available The antileishmanial activity of lapachol, isolapachol, and dihydrolapachol, along with soluble derivatives (potassium salt and acetate was obtained. All the compounds were assayed against metacyclic promastigotes of two different species of Leishmania associated to tegumentar leishmaniasis: L. amazonensis and L. braziliensis. All compounds presented significant activity, being isolapachol acetate the most active against promastigotes, with IC50/24h = 1.6 ± 0.0 µg/ml and 3.4 ± 0.5 µg/ml for, respectively, L. amazonensis and L. braziliensis. This compound was also assayed in vivo against L. amazonensis and showed to be active. Its toxicity in vitro was also established, and at concentration similar to the IC50, no toxicity was evidenced. In all experiments, pentamidine isethionate was used as a reference drug. The present results reinforce the potential use of substituted hydroxyquinones and derivatives as promising antileishmanial drugs and suggest a continuing study within this class of compounds.

  6. Antileishmanial activity of lapachol analogues.

    Science.gov (United States)

    Lima, Nadja M F; Correia, Clariane S; Leon, Leonor L; Machado, Gérzia M C; Madeira, Maria de Fátima; Santana, Antônio Euzébio G; Goulart, Marília O F

    2004-11-01

    The antileishmanial activity of lapachol, isolapachol, and dihydrolapachol, along with soluble derivatives (potassium salt) and acetate was obtained. All the compounds were assayed against metacyclic promastigotes of two different species of Leishmania associated to tegumentar leishmaniasis: L. amazonensis and L. braziliensis. All compounds presented significant activity, being isolapachol acetate the most active against promastigotes, with IC50/24h = 1.6 +/- 0.0 microg/ml and 3.4 +/- 0.5 microg/ml for, respectively, L. amazonensis and L. braziliensis. This compound was also assayed in vivo against L. amazonensis and showed to be active. Its toxicity in vitro was also established, and at concentration similar to the IC50, no toxicity was evidenced. In all experiments, pentamidine isethionate was used as a reference drug. The present results reinforce the potential use of substituted hydroxyquinones and derivatives as promising antileishmanial drugs and suggest a continuing study within this class of compounds.

  7. Tryptophan analogues. 1. Synthesis and antihypertensive activity of positional isomers.

    Science.gov (United States)

    Safdy, M E; Kurchacova, E; Schut, R N; Vidrio, H; Hong, E

    1982-06-01

    A series of tryptophan analogues having the carboxyl function at the beta-position was synthesized and tested for antihypertensive activity. The 5-methoxy analogue 46 exhibited antihypertensive activity in the rat via the oral route and was much more potent than the normal tryptophan analogue. The methyl ester was found to be a critical structural feature for activity.

  8. An Analogue of the Antibiotic Teicoplanin Prevents Flavivirus Entry In Vitro

    NARCIS (Netherlands)

    De Burghgraeve, Tine; Kaptein, Suzanne J. F.; Ayala Nunez, Nilda V.; Mondotte, Juan A.; Pastorino, Boris; Printsevskaya, Svetlana S.; de Lamballerie, Xavier; Jacobs, Michael; Preobrazhenskaya, Maria; Gamarnik, Andrea V.; Smit, Jolanda M.; Neyts, Johan

    2012-01-01

    There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We here report on an aglycon analogue of the antibiotic teicoplanin (code name LCTA-949) that inhibits DENV-induced cytopathic effect (CPE) in a

  9. Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?

    Science.gov (United States)

    Horvath, Gabriella A; Demos, Michelle; Shyr, Casper; Matthews, Allison; Zhang, Linhua; Race, Simone; Stockler-Ipsiroglu, Sylvia; Van Allen, Margot I; Mancarci, Ogan; Toker, Lilah; Pavlidis, Paul; Ross, Colin J; Wasserman, Wyeth W; Trump, Natalie; Heales, Simon; Pope, Simon; Cross, J Helen; van Karnebeek, Clara D M

    2016-01-01

    We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Potential Applications of Some Indigenous Bacteria Isolated from Polluted Areas in the Treatment of Brewery Effluents

    Directory of Open Access Journals (Sweden)

    Temesgen Oljira

    2018-01-01

    Full Text Available Biological wastewater treatment is economically feasible and ecofriendly. This study was aimed at isolating bacteria from brewery wastes and evaluating their bioremediation potential as individual isolate and/or their consortium in reducing the pollutants of brewery effluents. A total of 40 bacterial isolates were recovered and of these the three best isolates were selected. The selected bacteria were identified to genus level by using morphological and biochemical characteristics. Accordingly, the isolates were identified as Aeromonas sp., Pseudomonas sp., and Bacillus sp. After 12 days of incubation, the removal efficiency of these three isolates and their combinations for biological oxygen demand and chemical oxygen demand varied from 73.55% to 94.85% and 76.78% to 93.25%, respectively. Total nitrogen and phosphorus removal was within the range of 54.43% to 77.21% and 41.80% to 78.18%, respectively. Total suspended solid, total solid, and total dissolved solids removal ranged from 66.74% to 90.3%, 54.69% to 88.5%, and 53.02% to 88.2%, respectively. The pH and electrical conductivity values ranged from 6.81 to 8.65 and 3.31 mS/cm to 3.67 mS/cm, respectively. The treated effluent increased Beta vulgaris seeds germination from 80% to 100%, with mean germination time of 3.1 to 5.2 days and seedlings length of 2.3 cm to 6.3 cm. Therefore, the development of this finding into a large scale offers an attractive technology for brewery waste treatment.

  11. Profile of pridopidine and its potential in the treatment of Huntington disease: the evidence to date.

    Science.gov (United States)

    Squitieri, Ferdinando; de Yebenes, Justo Garcia

    2015-01-01

    Huntington disease (HD) is a chronic, genetic, neurodegenerative disease for which there is no cure. The main symptoms of HD are abnormal involuntary movements (chorea and dystonia), impaired voluntary movements (ie, incoordination and gait balance), progressive cognitive decline, and psychiatric disturbances. HD is caused by a CAG-repeat expanded mutation in the HTT gene, which encodes the huntingtin protein. The inherited mutation results in the production of an elongated polyQ mutant huntingtin protein (mHtt). The cellular functions of the Htt protein are not yet fully understood, but the functions of its mutant variant are thought to include alteration of gene transcription and energy production, and dysregulation of neurotransmitter metabolism, receptors, and growth factors. The phenylpiperidines pridopidine (4-[3-methanesulfonyl-phenyl]-1-propyl-piperidine; formerly known as ACR16) and OSU6162 ([S]-[-]-3-[3-methane [sulfonyl-phenyl]-1-propyl-piperidine) are members of a new class of pharmacologic agents known as "dopamine stabilizers". Recent clinical trials have highlighted the potential of pridopidine for symptomatic treatment of patients with HD. More recently, the analysis of HD models (ie, in vitro and in mice) highlighted previously unknown effects of pridopidine (increase in brain-derived neurotrophic factor, reduction in mHtt levels, and σ-1 receptor binding and modulation). These additional functions of pridopidine suggest it might be a neuroprotective and disease-modifying drug. Data from ongoing clinical trials of pridopidine will help define its place in the treatment of HD. This commentary examines the available preclinical and clinical evidence regarding the use of pridopidine in HD.

  12. Papillary ureteral neoplasm of low malignant potential in the upper urinary tract: endoscopic treatment.

    Science.gov (United States)

    Ercil, Hakan; Sener, Nevzat Can; Altunkol, Adem; Adamhasan, Fulya; Yesil, Suleyman; Ortoglu, Ferhat; Alma, Ergun; Gurbuz, Zafer Gokhan

    2014-12-01

    Papillary ureteral neoplasm of low malignant potential (PUNLMP) is a rare diagnosis, and to our knowledge, has not yet been reported in the upper urinary tract. In this study, we aimed to present our experience in managing a very rare diagnosis, PUNLMP, in the upper urinary tract, with endoscopic treatment. Files of patients who received surgery between January 2007 and January 2013 for upper urinary tract tumors were reviewed and patients treated for PUNLMP in the upper urinary tract in 4 urology clinics were reviewed. Patients included in the study had at most 2 tumors in the ureter and had a pathology of PUNLMP. The study included 11 patients with a mean age of 58.5 years. There were 9 men, and 2 women with a smoking rate of 81.8%. Nine patients (8 in the distal and 1 in the mid ureter) were managed using a semirigid ureteroscope. Two patients (1 with mid ureteral and 1 proximal) were treated using flexible ureteroscopy. The mean hospital stay was 1.56 days. Mean surgical time was 37.18 ± 7.14 minutes. The mean follow-up was 31.5 (range, 7-72) months. In the follow-ups, 3 patients had recurrences of 3, 2, and 4 mm in 9, 15, and 17 months, respectively. For tumors with a low risk of progression and relatively low risk of recurrence, organ-sparing treatments should be the choice of preference. To support our initial findings, randomized controlled studies on larger cohorts should be designed. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Potential Applications of Some Indigenous Bacteria Isolated from Polluted Areas in the Treatment of Brewery Effluents.

    Science.gov (United States)

    Oljira, Temesgen; Muleta, Diriba; Jida, Mulissa

    2018-01-01

    Biological wastewater treatment is economically feasible and ecofriendly. This study was aimed at isolating bacteria from brewery wastes and evaluating their bioremediation potential as individual isolate and/or their consortium in reducing the pollutants of brewery effluents. A total of 40 bacterial isolates were recovered and of these the three best isolates were selected. The selected bacteria were identified to genus level by using morphological and biochemical characteristics. Accordingly, the isolates were identified as Aeromonas sp., Pseudomonas sp., and Bacillus sp. After 12 days of incubation, the removal efficiency of these three isolates and their combinations for biological oxygen demand and chemical oxygen demand varied from 73.55% to 94.85% and 76.78% to 93.25%, respectively. Total nitrogen and phosphorus removal was within the range of 54.43% to 77.21% and 41.80% to 78.18%, respectively. Total suspended solid, total solid, and total dissolved solids removal ranged from 66.74% to 90.3%, 54.69% to 88.5%, and 53.02% to 88.2%, respectively. The pH and electrical conductivity values ranged from 6.81 to 8.65 and 3.31 mS/cm to 3.67 mS/cm, respectively. The treated effluent increased Beta vulgaris seeds germination from 80% to 100%, with mean germination time of 3.1 to 5.2 days and seedlings length of 2.3 cm to 6.3 cm. Therefore, the development of this finding into a large scale offers an attractive technology for brewery waste treatment.

  14. Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential

    Science.gov (United States)

    Zhu, Shimao; Guo, Caiping

    2016-01-01

    Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies. PMID:27801824

  15. Fluticasone-formoterol: a systematic review of its potential role in the treatment of asthma

    Directory of Open Access Journals (Sweden)

    Prosser TR

    2015-06-01

    Full Text Available Theresa R Prosser, Suzanne G Bollmeier St Louis College of Pharmacy, St Louis, MO, USA Background: The purpose of this systematic review is to summarize and evaluate the available published data regarding the efficacy and safety of a combination product containing fluticasone propionate/formoterol (FP-F in order to establish its potential role compared with other inhaled combination corticosteroid/long-acting beta2 receptor agonists for the maintenance treatment of asthma.Methods: A PubMed and EMBASE search was conducted using the terms “fluticasone propionate”, “formoterol fumarate”, “Flutiform®”, and “asthma” in July 2014 to identify trials using this combination specifically for the treatment of asthma. Additional information was gathered from references cited in the identified publications, the package insert, and the ClinicalTrials.gov registry. All randomized controlled clinical trials for humans in asthma were evaluated for inclusion. Data from animal trials, clinical trials for chronic obstructive pulmonary disease, and non-English sources were excluded.Results: Seven short-term safety and efficacy trials of FP-F compared with its individual components and two comparison trials of FP-F versus other combination products were identified. Generally, the incidence of drug-related adverse events was low and consistent with previously reported drug class-related adverse events (ie, pharyngitis, dysphonia, and headache. The combination of FP-F was shown to be noninferior to fluticasone propionate/salmeterol for improving predose forced expiratory volume at one second (FEV1 and 2 hours post dose FEV1. FP-F was also noninferior to budesonide/formoterol in improving predose FEV1. Other clinical endpoints, including various symptom scores, asthma control, quality of life, and subjects’ assessment of the medications were not significantly different.Conclusion: Poor asthma control is common. The data from short-term studies

  16. Arsenite oxidizing multiple metal resistant bacteria isolated from industrial effluent: their potential use in wastewater treatment.

    Science.gov (United States)

    Naureen, Ayesha; Rehman, Abdul

    2016-08-01

    Arsenite oxidizing bacteria, isolated from industrial wastewater, showed high resistance against arsenite (40 mM) and other heavy metals (10 mM Pb; 8 mM Cd; 6 mM Cr; 10 mM Cu and 26.6 mM As(5+)). Bacterial isolates were characterized, on the basis of morphological, biochemical and 16S rRNA ribotyping, as Bacillus cereus (1.1S) and Acinetobacter junii (1.3S). The optimum temperature and pH for the growth of both strains were found to be 37 °C and 7. Both the strains showed maximum growth after 24 h of incubation. The predominant form of arsenite oxidase was extracellular in B. cereus while in A. junii both types of activities, intracellular and extracellular, were found. The extracellular aresenite oxidase activity was found to be 730 and 750 µM/m for B. cereus and A. junii, respectively. The arsenite oxidase from both bacterial strains showed maximum activity at 37 °C, pH 7 and enhanced in the presence of Zn(2+). The presence of two protein bands with molecular weight of approximately 70 and 14 kDa in the presence of arsenic points out a possible role in arsenite oxidation. Arsenite oxidation potential of B. cereus and A. junii was determined up to 92 and 88 % in industrial wastewater after 6 days of incubation. The bacterial treated wastewater improved the growth of Vigna radiata as compared to the untreated wastewater. It indicates that these bacterial strains may find some potential applications in wastewater treatment systems to transform toxic arsenite into less toxic form, arsenate.

  17. Functionalized Ergot-alkaloids as potential dopamine D3 receptor agonists for treatment of schizophrenia

    Science.gov (United States)

    Ivanova, Bojidarka; Spiteller, Michael

    2012-12-01

    The relationship between the molecular structure and physical properties of functionalized naturally occurred Ergot-alkaloids as potential dopamine D3 receptor agonists is presented. The molecular modeling of the ergoline-skeleton is based on the comprehensive theoretical study of the binding affinity of the isolated chemicals towards the active sites of the D3 sub-type receptor (D3R) loops. The studied proton accepting ability under physiological conditions allows classifying four types of monocationics, characterizing with the different binding modes to D3R involving selected amino acid residues to the active sites. These results marked the pharmaceutical potential and clinical usage of the reported compounds as antipsychotic drugs for Schizophrenia treatment, since they allowed evaluating the highlights of the different hypothesizes of the biochemical causes the illness. The applied complex approach for theoretical and experimental elucidation, including quantum chemistry method, electrospray ionization (ESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometric (MS) methods, nuclear magnetic resonance and vibrational IR and Raman spectroscopy on the isolated fifteen novel derivatives (1)-(15) and their different protonated forms (1a)-(15a) evidenced a strong dependence of molecular conformation, physical properties and binding affinity. Thus, the semi-synthetic functionalization of the naturally occurred products (NPs), provided significant possibilities to further molecular drugs-design and development of novel derivatives with wanted biological function, using the established profile of selected classes/families of NPs. The work described chiefly the non-linear (NL) approach for the interpretation of the mass chromatograms on the performed hybrid high performance liquid chromatography (HPLC) tandem MS/MS and MS/MS/MS experiments, discussing the merits and great diversity of instrumentation flexibility, thus achieving fundamental

  18. Thematic Research network for emergency and UnScheduled Treatment (TRUST: scoping the potential

    Directory of Open Access Journals (Sweden)

    Edwards Adrian

    2008-01-01

    Full Text Available Abstract Background To identify the benefits of a network in emergency and unscheduled care research, a six week scoping study was undertaken. Objectives were to: draw together stakeholders; identify and prioritise research topics; identify sites for recruitment to studies; and agree a research strategy for a network. Methods A workshop was held to discuss and agree a research strategy based on results from four activities: visits to established research centres in emergency and unscheduled care; a literature overview; interviews with stakeholders in a GP out-of-hours service; and an exploration of the potential for routine data to support research in emergency care. Results Participants attended the workshop from user groups, primary care, the ambulance service, social care, the national telephone based health helpline, the Welsh Assembly Government and the academic sector. Site visits identified opportunities for collaboration. Gaps in knowledge were identified concerning the effectiveness of alternative models of emergency care delivery. Interview data highlighted a lack of evidence related to the quality of out-of-hours provision of primary care. The All Wales Injury Surveillance System (AWISS was found to offer the potential to use routine data to support quantitative studies in emergency care. Three key issues emerged across all activities: working across boundaries; patient involvement; and triage. Conclusion The study included views from patient, provider, policy and academic perspectives and built the case for a research network in emergency care. Now funded, TRUST (Thematic Research network for emergency and UnScheduled Treatment will allow the development of research proposals, building of research teams and recruitment of sites and patients both in Wales and across the UK. It aims to address the imbalance between investment and research in this area and help support provision of 'the right care to the right people at the right time'.

  19. Melatonin potentiates “inside-out” nano-thermotherapy in human breast cancer cells: a potential cancer target multimodality treatment based on melatonin-loaded nanocomposite particles

    Science.gov (United States)

    Xie, Wensheng; Gao, Qin; Wang, Dan; Wang, Wei; Yuan, Jie; Guo, Zhenhu; Yan, Hao; Wang, Xiumei; Sun, Xiaodan; Zhao, Lingyun

    2017-01-01

    Purpose With the wide recognition of oncostatic effect of melatonin, the current study proposes a potential breast cancer target multimodality treatment based on melatonin-loaded magnetic nanocomposite particles (Melatonin-MNPs). Methods Melatonin-MNPs were fabricated by the single emulsion solvent extraction/evaporation method. Results Based on the facilitated transport of melatonin by the GLUT overexpressed on the cell membrane, such Melatonin-MNPs can be more favorably uptaken by MCF-7 cells compared with the melatonin-free nanocomposite particles, which indicates the cancer targeting ability of melatonin molecule. Inductive heating can be generated by exposure to the Melatonin-MNPs internalized within cancer cells under alternative magnetic field, so as to achieve the “inside-out” magnetic nano-thermotherapy. In addition to demonstrating the superior cytotoxic effect of such nano-thermotherapy over the conventional exogenous heating by metal bath, more importantly, the sustainable release of melatonin from the Melatonin-MNPs can be greatly promoted upon responsive to the magnetic heating. The multimodality treatment based on Melatonin-MNPs can lead to more significant decrease in cell viability than any single treatment, suggesting the potentiated effect of melatonin on the cytotoxic response to nano-thermotherapy. Conclusion This study is the first to fabricate the precisely engineered melatonin-loaded multifunctional nanocomposite particles and demonstrate the potential in breast cancer target multimodality treatment. PMID:29066887

  20. Melatonin potentiates "inside-out" nano-thermotherapy in human breast cancer cells: a potential cancer target multimodality treatment based on melatonin-loaded nanocomposite particles.

    Science.gov (United States)

    Xie, Wensheng; Gao, Qin; Wang, Dan; Wang, Wei; Yuan, Jie; Guo, Zhenhu; Yan, Hao; Wang, Xiumei; Sun, Xiaodan; Zhao, Lingyun

    2017-01-01

    With the wide recognition of oncostatic effect of melatonin, the current study proposes a potential breast cancer target multimodality treatment based on melatonin-loaded magnetic nanocomposite particles (Melatonin-MNPs). Melatonin-MNPs were fabricated by the single emulsion solvent extraction/evaporation method. Based on the facilitated transport of melatonin by the GLUT overexpressed on the cell membrane, such Melatonin-MNPs can be more favorably uptaken by MCF-7 cells compared with the melatonin-free nanocomposite particles, which indicates the cancer targeting ability of melatonin molecule. Inductive heating can be generated by exposure to the Melatonin-MNPs internalized within cancer cells under alternative magnetic field, so as to achieve the "inside-out" magnetic nano-thermotherapy. In addition to demonstrating the superior cytotoxic effect of such nano-thermotherapy over the conventional exogenous heating by metal bath, more importantly, the sustainable release of melatonin from the Melatonin-MNPs can be greatly promoted upon responsive to the magnetic heating. The multimodality treatment based on Melatonin-MNPs can lead to more significant decrease in cell viability than any single treatment, suggesting the potentiated effect of melatonin on the cytotoxic response to nano-thermotherapy. This study is the first to fabricate the precisely engineered melatonin-loaded multifunctional nanocomposite particles and demonstrate the potential in breast cancer target multimodality treatment.

  1. Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Chun-Chieh Wu

    2015-05-01

    Full Text Available Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment. Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p < 0.0001. Nude mouse (BALB/c-nu experiments showed that the increased tumor volume ratios in colchicine-treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167. The tumor growth rates in colchicine-treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015. In addition to the well-known direct colchicine–tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase-polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT-COI. There was no effect of colchicine on MT-COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long-standing prescription experience.

  2. Clinical potential of eliglustat tartrate in the treatment of type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Kaplan P

    2014-05-01

    Full Text Available Paige KaplanLysosomal Disorders Center, Section of Metabolic Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USAAbstract: Nonneuropathic type 1 Gaucher disease is an autosomal recessive inherited disease caused by the deficiency or absence of beta glucocerebrosidase (beta glucosidase. The highest prevalence of type 1 is in Ashkenazi Jews, but it affects all ethnic groups. It manifests at any age but is seen predominantly in the first two decades. The phenotype is characterized by painless splenomegaly and secondary hypersplenism (low hemoglobin concentration and low platelet and white blood cell counts. Symptoms and signs include splenomegaly; chronic fatigue, frequent nose bleeds, prolonged bleeding, and/or bruising; hepatomegaly; bone pain, bone destruction and low bone density; and poor growth in childhood and delayed pubertal development. Current treatment with intravenous enzyme replacement has been generally successful. However, oral treatments have been developed because enzyme replacement is time-consuming and invasive, and intravenous infusions are not universally available for patients who live far from medical centers or home infusion nurses. Furthermore, it may become difficult to access veins after repeated infusions. Orally administered substrate reduction is a newer treatment approach. The aim is to limit the synthesis of the substrate, glucosylceramide. The residual intrinsic enzyme, acting alone or with recombinant enzyme, can then completely catabolize the smaller amounts of glucosylceramide that are transported into lysosomes. Eliglustat tartrate is a new specific inhibitor of glucosylceramide synthase. Phase III trials in humans have been completed. Eliglustat tartrate has been shown to be efficacious and safe in adult humans. The results are as good or better compared with intravenous replacement with regard to reductions in spleen and liver enlargement and improvements in hemoglobin concentrations, platelet

  3. THE USE OF PANAX GINSENG AND ITS ANALOGUES AMONG PHARMACY CUSTOMERS IN ESTONIA: A CROSS-SECTIONAL STUDY.

    Science.gov (United States)

    Volmer, Dasy; Raal, Ain; Kalle, Raivo; Sõukand, Renata

    2016-01-01

    The aim of the cross-sectional study was to evaluate the pattern of complementary self-treatment with P. ginseng and its analogues amongst pharmacy customers in Estonia. The study instrument consisted of multiple-choice items related to personal knowledge about and experience with the use of P. ginseng and its analogues. In total, 1233 customers participated in the study. Of study participants, 18.1% reported the use of P. ginseng and its analogues in their lives. P. ginseng preparations were used mostly according to the well- known indications (tiredness, weakness and decreased mental and physical capacity). Of P. ginseng users 44.3% reported positive treatment effects and 12.0% had experienced different side effects. With increase of age (p < 0.01) and at lower levels of education (p = 0.04), the use of ginseng or its analogues decreased. The better the users evaluated their health, the better they perceived the effect of P. ginseng preparations (p < 0.01). This study reported rather frequent use of P. ginseng and its analogues. P. ginseng could be seen in the treatment of conditions, where the use of local medicinal plants has not been established. Further research is needed to learn more about public knowledge and experiences about efficacy and safety of P. ginseng and its analogues.

  4. The effect of synthetic ceramide analogues on gastritis and esophagitis in rats.

    Science.gov (United States)

    Kim, Sung Hyo; Um, Seung In; Nam, Yoonjin; Park, Sun Young; Dong, Je Hyun; Ko, Sung Kwon; Sohn, Uy Dong; Lee, Sang Joon

    2016-09-01

    The effects of ceremide analogues on esophagitis and gastritis in rats were examined. Gastritis induced by indomethacin was significantly reduced after CY3325 and CY3723 treatment, whereas other analogues had no effect. The amount of malondialdehyde in gastritis was significantly reduced by CY3325 or CY 3723. CY3325 or CY 3723 decreased the glutathione levels in gastritis. The myeloperoxidase level in gastritis is increased, and its increment was decreased by CY3325 and CY3723. In reflux esophagitis, the ulceration was decreased by CY3325, CY3723. The gastric volume and acid output are reduced, whereas the pH value is increased by CY3325 or CY3723 after esophagitis. These results suggest that ceramide analogues, CY3325 and CY3723, can prevent the development of gastritis and reflux esophagitis in rats.

  5. Synthesis and Biological Evaluation of New (−)‐Englerin Analogues

    Science.gov (United States)

    López‐Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T.

    2016-01-01

    Abstract We report the synthesis and biological evaluation of a series of (−)‐englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier‐to‐synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth‐inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC). PMID:27005578

  6. Effects of Fungicide Treatment on Free Amino Acid Concentration and Acrylamide-Forming Potential in Wheat.

    Science.gov (United States)

    Curtis, Tanya Y; Powers, Stephen J; Halford, Nigel G

    2016-12-28

    Acrylamide forms from free asparagine and reducing sugars during frying, baking, roasting, or high-temperature processing, and cereal products are major contributors to dietary acrylamide intake. Free asparagine concentration is the determining factor for acrylamide-forming potential in cereals, and this study investigated the effect of fungicide application on free asparagine accumulation in wheat grain. Free amino acid concentrations were measured in flour from 47 varieties of wheat grown in a field trial in 2011-2012. The wheat had been supplied with nitrogen and sulfur and treated with growth regulators and fungicides. Acrylamide formation was measured after the flour had been heated at 180 °C for 20 min. Flour was also analyzed from 24 (of the 47) varieties grown in adjacent plots that were treated in identical fashion except that no fungicide was applied, resulting in visible infection by Septoria tritici, yellow rust, and brown rust. Free asparagine concentration in the fungicide-treated wheat ranged from 1.596 to 3.987 mmol kg -1 , with a significant (p fungicide treatment, the increases in acrylamide ranging from 2.7 to 370%. Free aspartic acid concentration also increased, whereas free glutamic acid concentration increased in some varieties but decreased in others, and free proline concentration decreased. The study showed disease control by fungicide application to be an important crop management measure for mitigating the problem of acrylamide formation in wheat products.

  7. Polygonum multiflorum root extract as a potential candidate for treatment of early graying hair

    Directory of Open Access Journals (Sweden)

    Nguyen Dinh Thang

    2017-01-01

    Full Text Available Despite Polygonum multiflorum (PM has been experiencely used as a drug to treat early graying hair phenomenon in Asian countries for a long time, there is limited study examined the real biological effects of PM on hair graying in vitro and in vivo. In this study, we investigated the effects of PM root extract (PM-RE on melanin synthesis in human melanoma SKMEL-28 cells and embryos/larvae of wild-type strain AB zebrafish. We also preliminary revealed the molecular mechanism of early hair graying phenomenon in both in vitro and in vivo models. Our results showed that PM-RE significantly induced melanin synthesis in melanin-producing SKMEL-28 melanoma cells and also in zebrafish embryos/larvae at 4-day postfertilization through activation of MC1R/MITF/tyrosinase-signaling pathway. We also investigated the differences in genotype between graying hair follicle and black hair follicle of young peoples and found that early hair graying phenomenon may be related to downregulation of MC1R/MITF/tyrosinase pathway. Taken together, we suggested that PM-RE at safe doses could be used as a potential agent for the treatment of early hair graying and other loss pigmentation-related diseases.

  8. Augmented simvastatin cytotoxicity using optimized lipid nanocapsules: a potential for breast cancer treatment.

    Science.gov (United States)

    Safwat, Sally; Hathout, Rania M; Ishak, Rania A; Mortada, Nahed D

    2017-03-01

    We noticed paucity in exploiting solutol-based lipid nanocapsules in statins formulations though they carry all favorable properties that are needed for cancer passive targeting such as their small particle size, stealth properties, ability to highly accommodate lipophilic drugs, good internalization and P-gp pump inhibition. The aim of this study was to design and optimize new simvastatin drug delivery systems; lipid nanocapsules intended for administration through the intravenous route as potential treatment for breast cancer. Optimized nanocapsules were prepared by the phase-inversion method according to a D-optimal mixture design, characterized and assessed for their cytotoxicity. Three successful models for particle size, polydispersity index (PDI) and percentage of drug released after 48 h were generated. The prepared lipid nanocapsules acquired spherical and homogenous morphology, good stability and tolerance to sterilization. The obtained release profiles demonstrated desired sustained release pattern. Furthermore, testing selected formulations on human breast cancer adenocarcinoma cells showed augmented cytotoxicity of simvastatin reaching low IC50 values as 1.4 ± 0.02 μg/ml compared to the pure drug. The proposed lipid nanocapsules pose promising candidates as simvastatin carriers intended for the targeting of breast cancer.

  9. Potential mechanisms underlying anxiety and depression in Parkinson's disease: consequences of L-DOPA treatment

    Science.gov (United States)

    Eskow Jaunarajs, Karen L.; Angoa-Perez, Mariana; Kuhn, Donald M.; Bishop, Christopher

    2010-01-01

    Though the most recognizable symptoms of Parkinson's disease (PD) are motor-related, many patients also suffer from debilitating affective symptoms that deleteriously influence quality of life. Dopamine (DA) loss is likely involved in the onset of depression and anxiety in PD. However, these symptoms are not reliably improved by DA replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA). In fact, preclinical and clinical evidence suggests that L-DOPA treatment may worsen affect. Though the neurobiological mechanisms remain unclear, recent research contends that L-DOPA further perturbs the function of the norepinephrine and serotonin systems, already affected by PD pathology, which have been intimately linked to the development and expression of anxiety and depression. As such, this review provides an overview of the clinical characteristics of affective disorders in PD, examines the utility of animal models for the study of anxiety and depression in PD, and finally, discusses potential mechanisms by which DA loss and subsequent L-DOPA therapy influence monoamine function and concomitant affective symptoms. PMID:20615430

  10. Membrane distillation for wastewater reverse osmosis concentrate treatment with water reuse potential

    KAUST Repository

    Naidu, Gayathri

    2016-11-29

    Membrane distillation (MD) was evaluated as a treatment option of wastewater reverse osmosis concentrate (WWROC) discharged from wastewater reclamation plants (WRPs). A direct contact MD (DCMD), at obtaining 85% water recovery of WWROC showed only 13–15% flux decline and produced good quality permeate (10–15 µS/cm, 99% ion rejection) at moderate feed temperature of 55 °C. Prevalent calcium carbonate (CaCO3) deposition on the MD membrane occurred in treating WWROC at elevated concentrations. The combination of low salinity and loose CaCO3 adhesion on the membrane did not significantly contribute to DCMD flux decline. Meanwhile, high organic content in WWROC (58–60 mg/L) resulted in a significant membrane hydrophobicity reduction (70% lower water contact angle than virgin membrane) attributed to low molecular weight organic adhesion onto the MD membrane. Granular activated carbon (GAC) pretreatment helped in reducing organic contents of WWROC by 46–50%, and adsorbed a range of hydrophobic and hydrophilic micropollutants. This ensured high quality water production by MD (micropollutants-free) and enhanced its reuse potential. The MD concentrated WWROC was suitable for selective ion precipitation, promising a near zero liquid discharge in WRPs.

  11. Potential Pharmacologic Treatments for Cystinuria and for Calcium Stones Associated with Hyperuricosuria

    Energy Technology Data Exchange (ETDEWEB)

    Goldfarb, David S. (NYUSM)

    2012-03-14

    Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to 'salt out' (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent calcium stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of L-cystine methyl ester and L-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, L-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria.

  12. Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

    Directory of Open Access Journals (Sweden)

    Deepak P

    2016-11-01

    Full Text Available Parakkal Deepak, Edward V Loftus Jr Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA Abstract: Crohn’s disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23 pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis. Very promising data have emerged through phase II and phase III trials (UNITI-1, UNITI-2, and IM-UNITI for both induction and maintenance of clinical response and remission in moderate-to-severe Crohn’s disease, resulting in approval by the Food and Drug Administration for this condition. This article reviews the immunology of the IL-12/23 pathway, available data regarding the initial designing of ustekinumab, drug development through clinical trials including pharmacokinetics, efficacy, and safety, and its potential place in the treatment of Crohn’s disease.Keywords: ustekinumab, Crohn’s disease, inflammatory bowel disease, interleukin-12/23 monoclonal antibody, interleukin-12, interleukin-23

  13. Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury.

    Science.gov (United States)

    Abouzied, Mekky M; Eltahir, Heba M; Taye, Ashraf; Abdelrahman, Mahran S

    2016-01-01

    Oxidative stress is one of the mechanisms involved in the acute carbon tetrachloride (CCl4)-induced hepatotoxicity. Since 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, known as tempol, has powerful antioxidant properties, we investigated its potential hepatoprotective effects and the underlying mechanisms that may add further benefits for its clinical usefulness using an acute model of CCl4-induced hepatotoxicity. One hour after CCl4 induction of acute hepatotoxicity, mice were treated with a daily dose of 20 mg/kg/day tempol for 3 days. It was found that <