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Sample records for analogues potential treatment

  1. Therapeutic Potential of Thalidomide and Its Analogues in the Treatment of Cancer.

    Science.gov (United States)

    Sherbet, Gajanan V

    2015-11-01

    Thalidomide was synthesised and launched several decades ago as a drug against respiratory infections and was administered to pregnant women for relief of morning sickness. The drug was withdrawn when its teratogenic effects came to light. Thalidomide and its analogues suppressed cell proliferation and angiogenesis and controlled invasion and metastasis of tumours in pre-clinical studies. With the recognition of its immunomodulatory and anti-inflammatory, properties, thalidomide may have found a place in the treatment of many forms of cancer and autoimmune conditions. Herein the signalling pathways modulated by thalidomides via the mediation of vascular endothelial growth factor, phosphoinositide-kinase/protein kinase B and nuclear factor kappa B, and mammalian target of rapamycin, which integrates these signalling systems, are discussed. The mode of action of thalidomides and their strategic utility in therapy are evaluated in the context of potential clinical benefits. Notwithstanding the perceived benefits, the side-effects of thalidomides need to be taken into account; they do exert teratogenic effects in animal models, although being effective at lower doses, the drugs seem to show comparatively manageable and reduced toxicity. Combination therapy of thalidomides and modulators of signaling that they influence may further reduce the severity of the side-effects by delivering inhibitory effects at reduced drug dosages. Pre-clinical evaluations of this kind seem warranted. PMID:26503997

  2. Therapeutic Potential of Thalidomide and Its Analogues in the Treatment of Cancer.

    Science.gov (United States)

    Sherbet, Gajanan V

    2015-11-01

    Thalidomide was synthesised and launched several decades ago as a drug against respiratory infections and was administered to pregnant women for relief of morning sickness. The drug was withdrawn when its teratogenic effects came to light. Thalidomide and its analogues suppressed cell proliferation and angiogenesis and controlled invasion and metastasis of tumours in pre-clinical studies. With the recognition of its immunomodulatory and anti-inflammatory, properties, thalidomide may have found a place in the treatment of many forms of cancer and autoimmune conditions. Herein the signalling pathways modulated by thalidomides via the mediation of vascular endothelial growth factor, phosphoinositide-kinase/protein kinase B and nuclear factor kappa B, and mammalian target of rapamycin, which integrates these signalling systems, are discussed. The mode of action of thalidomides and their strategic utility in therapy are evaluated in the context of potential clinical benefits. Notwithstanding the perceived benefits, the side-effects of thalidomides need to be taken into account; they do exert teratogenic effects in animal models, although being effective at lower doses, the drugs seem to show comparatively manageable and reduced toxicity. Combination therapy of thalidomides and modulators of signaling that they influence may further reduce the severity of the side-effects by delivering inhibitory effects at reduced drug dosages. Pre-clinical evaluations of this kind seem warranted.

  3. Somatostatin analogue treatment of neuroendocrine tumours.

    OpenAIRE

    de Herder, W. W.; van der Lely, A.J.; Lamberts, S. W.

    1996-01-01

    The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically 'nonfunctioning' pituitary tumours are still uncertain. So...

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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. PMID:27039807

  6. Design, synthesis and biological evaluation of novel hamamelitannin analogues as potentiators for vancomycin in the treatment of biofilm related Staphylococcus aureus infections.

    Science.gov (United States)

    Vermote, Arno; Brackman, Gilles; Risseeuw, Martijn D P; Coenye, Tom; Van Calenbergh, Serge

    2016-10-01

    Staphylococcus aureus is a frequent cause of biofilm-related infections. Bacterial cells within a biofilm are protected from attack by the immune system and conventional antibiotics often fail to penetrate the biofilm matrix. The discovery of hamamelitannin as a potentiator for antibiotics, recently led to the design of a more drug-like lead. In the present study, we want to gain further insight into the structure-activity relationship (S.A.R.) of the 5-position of the molecule, by preparing a library of 21 hamamelitannin analogues. PMID:27507109

  7. Generalised insulin oedema after intensification of treatment with insulin analogues

    OpenAIRE

    Adamo, Luigi; Thoelke, Mark

    2013-01-01

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  8. Combined treatment of somatostatin analogues with pegvisomant in acromegaly

    NARCIS (Netherlands)

    S.E. Franck; A. Muhammad; A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)

    2016-01-01

    textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups ha

  9. Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.

    Science.gov (United States)

    Yadav, Babasaheb; Taurin, Sebastien; Rosengren, Rhonda J; Schumacher, Marc; Diederich, Marc; Somers-Edgar, Tiffany J; Larsen, Lesley

    2010-09-15

    A series of 18 heterocyclic cyclohexanone analogues of curcumin have been synthesised and screened for their activity in both adherent and non-adherent cancer cell models. Cytotoxicity towards MBA-MB-231 breast cancer cells, as well as ability to inhibit NF-kappaB transactivation in non-adherent K562 leukemia cells were investigated. Three of these analogues 3,5-bis(pyridine-4-yl)-1-methylpiperidin-4-one B1, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one B10, and 8-methyl-2,4-bis((pyridine-4-yl)methylene)-8-aza-bicyclo[3.2.1]octan-3-one C1 showed potent cytotoxicity towards MBA-MB-231, MDA-MB-468, and SkBr3 cell lines with EC50 values below 1 microM and inhibition of NF-kappaB activation below 7.5 microM. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18 h. This level of activity warrants further investigation for the treatment of ER-negative breast cancer and/or chronic myelogenous leukemia as prototypical cellular models for solid and liquid tumors.

  10. 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.

  11. Long Acting Somatostatin Analogue: Clinical Potential for Gastrointestinal Disease

    OpenAIRE

    Richard N Fedorak

    1989-01-01

    Name somatostatin is found throughout the gastrointestinal tract and has a wide variety of biological actions. Nevertheless, its short biological half-life and limited stability necessitate its use via continuous parenteral infusion and, thus, limits its therapeutic usefulness The development of long acting somatostatin analogues have lead to a re-examination of the therapeutic usefulness of somatostatin in gastrointestinal disease. Somatostatin analogues appear most beneficial tn preventing ...

  12. Combined treatment of somatostatin analogues with pegvisomant in acromegaly.

    Science.gov (United States)

    Franck, S E; Muhammad, A; van der Lely, A J; Neggers, S J C M M

    2016-05-01

    Treatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups has recommended switching to combined treatment of LA-SSA and pegvisomant (PEGV) in patients with partial response to LA-SSAs. This combination of LA-SSA and PEGV, a growth hormone receptor antagonist, can normalize IGF-I levels in virtually all patients, requiring that the adequate dose of PEGV is used. The required PEGV dose varies significantly between individual acromegaly patients. One of the advantages of the combination therapy is that tumor size control or even tumor shrinkage can be observed in a vast majority of patients. The main side effects of the combination treatment are gastrointestinal symptoms, lipohypertrophy and transient elevated liver transaminases. In this review we provide an overview of the efficacy and safety of the combined treatment of LA-SSAs with PEGV. PMID:26661938

  13. Neurotoxicity Caused by the Treatment with Platinum Analogues

    Directory of Open Access Journals (Sweden)

    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.

  14. Development of labelled somatostatin and its analogues for the diagnosis and treatment of tumors

    International Nuclear Information System (INIS)

    For recent years, the labelling and application of Somatostatin and Its Analogues have been becoming more and more important in the both diagnosis and treatment of a variety of tumors, especially the neuroendocrine tumors. This paper's goals are to deal with the chemical aspects of the radiolabelling of somatostatin and its analogues. It reviews the selected radionuclide and bifunctional chelating agents may be used in the labeling of Somatostatin and its analogues are comparatively assessed. (author). 30 refs., 3 tabs

  15. Effects of quantum potential on lower dimensional models of analogue gravity

    Science.gov (United States)

    Sarkar, Supratik; Bhattacharyay, Arijit

    2016-01-01

    We address the issues related to the presence of the quantum potential term in a BEC on the observable analogue gravity systems. We show that the quantum potential term apparently gives rise to massive scalar excitations of length scales of the order O (1 /ξ ) in the lower dimensional space. Since, in "analogue models", there is a window for experimental observations generally in (2 +1 ) or even lower dimensional space, one has to take proper account of the presence of these massive excitations to interpret the results.

  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. Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs.

    Science.gov (United States)

    Murray, Michael; Hraiki, Adam; Bebawy, Mary; Pazderka, Curtis; Rawling, Tristan

    2015-06-01

    Lipids have the potential for development as anticancer agents. Endogenous membrane lipids, such as ceramides and certain saturated fatty acids, have been found to modulate the viability of tumor cells. In addition, many tumors over-express cyclooxygenase, lipoxygenase or cytochrome P450 enzymes that mediate the biotransformation of ω-6 polyunsaturated fatty acids (PUFAs) to potent eicosanoid regulators of tumor cell proliferation and cell death. In contrast, several analogous products from the biotransformation of ω-3 PUFAs impair particular tumorigenic pathways. For example, the ω-3 17,18-epoxide of eicosapentaenoic acid activates anti-proliferative and proapoptotic signaling cascades in tumor cells and the lipoxygenase-derived resolvins are effective inhibitors of inflammatory pathways that may drive tumor expansion. However, the development of potential anti-cancer drugs based on these molecules is complex, with in vivo stability a major issue. Nevertheless, recent successes with the antitumor alkyl phospholipids, which are synthetic analogues of naturally-occurring membrane phospholipid esters, have provided the impetus for development of further molecules. The alkyl phospholipids have been tested against a range of cancers and show considerable activity against skin cancers and certain leukemias. Very recently, it has been shown that combination strategies, in which alkyl phospholipids are used in conjunction with established anticancer agents, are promising new therapeutic approaches. In future, the evaluation of new lipid-based molecules in single-agent and combination treatments may also be assessed. This could provide a range of important treatment options in the management of advanced and metastatic cancer. PMID:25603423

  18. Nucleos(tide analogues treatment outcome in genotype B and C chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Myo Nyein Aung

    2010-01-01

    Full Text Available Background : Hepatitis B genotypes influence the course and severity of the disease. Aim: To compare the treatment outcome of chronic hepatitis B genotype B and C patients after treating with nucleos(tide analogues for six months. Patients and Methods: Forty chronic hepatitis B patients attending the liver clinic of Hospital for Tropical diseases, Bangkok, were studied in retrospective cohort design. Six genotype B patients (15% and thirty-four genotype C patients (85% were treated. Serum hepatitis B viral load , serum alanine amino transferase level, HBeAg status and alpha-feto protein level were measured at the time of starting nucleos(t analogues therapy, and six months later. Besides, achievement of undetectable viral load was assessed in patients with normal serum alanine amino transferase compared to patients with high serum alanine amino transferase level. Results: After six months of nucleos (t analogues treatment, achievement of undetectable hepatitis B viral load was higher in genotype B patients (66.7% than in genotype C patients (42.4% (Relative Risk=1.57, 0.79-3.14. Biochemical remission, HBeAg seroconversion and tumor marker levels between the two groups were not significantly different. Moreover, achievement of undetectable hepatitis B viral load was significantly higher in normal alanine amino transferase level (75% than in patients with high serum alanine amino transferase level (33.3% on nucleos(tide analogue treatment (Relative Risk=2.25, 1.20- 4.20. Conclusion: Chronic hepatitis B treatment outcome between genotype B and C were not significantly different. Patients with normalized serum alanine amino transferase level tend to achieve undetectable viral load after nucleoside analogues treatment.

  19. Control of proliferating potential of myeloid leukemia cells during long-term treatment with vitamin D3 analogues and other differentiation inducers in combination with antileukemic drugs: in vitro and in vivo studies.

    Science.gov (United States)

    Kasukabe, T; Honma, Y; Hozumi, M; Suda, T; Nishii, Y

    1987-01-15

    Growth inhibition of murine and human myeloid leukemia cells by differentiation inducers during long-term culture was examined to improve the strategy for therapy of myeloid leukemia by differentiation inducers. When the effect of 1 alpha,25-dihydroxyvitamin D3, a typical differentiation inducer, on proliferation of mouse myeloid leukemia M1 cells was examined at a constant product of time and concentration (480 nM in 20 days), the continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3 was the most effective for inhibition of cell proliferation. After 20 days, the cumulative cell number was reduced about 3 X 10(5) times by continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. Similar results were obtained when M1 cells were treated continuously with dexamethasone. M1 cells resistant to 1 alpha,25-dihydroxyvitamin D3 appeared about 25 days after the start of continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. On the other hand, when M1 cells were treated continuously with 1 alpha,25-dihydroxyvitamin D3 and noncytotoxic doses of antileukemic drugs such as 1-beta-D-arabinofuranosylcytosine and daunomycin, resistant cells did not appear for at least 35 days. A similar effect of 1 alpha,25-dihydroxyvitamin D3 and antileukemic drugs on cell proliferation was observed with the human monoblast-like cell line U937. The survival of syngeneic SL mice inoculated with M1 cells was prolonged more by treatment with both 1 alpha-hydroxyvitamin D3 and daunomycin than by treatment with either drug alone. These results suggest that continuous treatment with both differentiation inducers and certain antileukemic drugs may be more effective therapeutically than treatment with a differentiation inducer alone.

  20. Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases.

    Science.gov (United States)

    Basith, Shaherin; Cui, Minghua; Hong, Sunhye; Choi, Sun

    2016-01-01

    Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions. PMID:27455231

  1. Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases

    Directory of Open Access Journals (Sweden)

    Shaherin Basith

    2016-07-01

    Full Text Available Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions.

  2. Current Status of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases

    OpenAIRE

    Pawel Robak; Ewa Lech-Maranda; Tadeusz Robak; Anna Korycka

    2009-01-01

    For the past few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and become available for either in vitro studies or clinical trials. Among them the class of antineoplastic drugs belonging to the purine nucleoside analogues group (PNAs) plays an important role. Three of them: pentostatin (DCF), cladribine (2-CdA) and fludarabine (FA) were approved by Food and Drug Administration (FDA) for the treatment of hematological malig...

  3. Plumbagin, Vitamin K3 Analogue, Suppresses STAT3 Activation Pathway through Induction of Protein Tyrosine Phosphatase, SHP-1: Potential Role in Chemosensitization

    OpenAIRE

    Sandur, Santosh K.; Pandey, Manoj K.; Sung, Bokyung; Aggarwal, Bharat B.

    2010-01-01

    The activation of STAT3 has been linked with carcinogenesis through survival, proliferation, and angiogenesis of tumor cells. Agents that can suppress STAT3 activation have potential not only for prevention but also for treatment of cancer. In the present report, we investigated whether plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), an analogue of Vitamin K and isolated from chitrak (Plumbago zeylanica), an Ayurvedic medicinal plant, can modulate the STAT3 pathway. We found that plumbagin...

  4. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    Science.gov (United States)

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-09-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Aryl chain analogues of the biotin vitamers as potential herbicides. Part 3.

    Science.gov (United States)

    Ashkenazi, Tali; Pinkert, Dalia; Nudelman, Ayelet; Widberg, Ayala; Wexler, Barry; Wittenbach, Vernon; Flint, Dennis; Nudelman, Abraham

    2007-10-01

    Novel aryl chain isosters and analogues of 7-keto-8-aminopelargonic acid (KAPA) and 7,8-diaminopelargonic acid (DAPA), the vitamer intermediates involved in the biosynthetic pathway of biotin, possessing chain lengths of eight carbon atoms, were prepared and evaluated as potential herbicides. In the greenhouse test the most active compounds were the fluorinated derivative 9d and the selenophenyl/furan mixture 17m/17p, which were most active against Foxtail millet. In the more sensitive Arabidopsis test the most active substances were 9a and 17m, which displayed GR(50) (concentration of active compound causing 50% growth inhibition) values of 0.2 and 0.5 mg kg(-1) respectively (values of < 50 mg kg(-1) are considered herbicidal).

  7. Primary study of a novel Tc-tricarbonyl cocaine analogue as the potential DAT imaging agent

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiaobo; ZHU Lin; DING Shaoke; LIU Boli

    2005-01-01

    The convenient preparation of organometallic precursor fac-[99mTc(CO)3 (H2O)3]+ opens a new route to design new radiopharmaceuticals. Based on this precursor, a new cocaine analogue, Tropyn, is designed and synthesized, and "2+1" mixed-ligands approach is used to prepare a neutral complex [99mTc(CO)3(Tropyn)I]. Biodistribution in mice and rats proves that it has sufficient brain uptake. Rat regional brain biodistribution indicates that the complex is highly concentrated in the striatum (ST) with rapid clearance in the cortex (CT) and hippocampus (HP), which make it valuable for further investigation as the potential Second-Generation DAT imaging agent.

  8. Pros and cons of peginterferon versus nucleos(t)ide analogues for treatment of chronic hepatitis B

    NARCIS (Netherlands)

    M.J. Sonneveld (Milan); H.L.A. Janssen (Harry)

    2010-01-01

    textabstractThe emergence of new and more potent treatment options has markedly changed the treatment landscape of chronic hepatitis B. Both peginterferon and nucleos(t)ide analogues have considerable advantages and limitations, and current treatment guidelines refrain from clearly suggesting a firs

  9. The role of insulin analogues in the current treatment of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mitrović Milena

    2006-01-01

    Full Text Available Introduction. Ever since insulin was discovered by Banting and Best in 1921, all further researches in this field had been conducted with one goal: to find new insulin molecules which would provide better glycemic control with fewer side effects i.e. to mimic endogenous physiological insulin secretion. Normal insulin secretion. In healthy individuals, endogenous insulin secretion can be classified as basal (which provides basal glucose homeostasis and stimulated (as a response to a meal. Conventional insulin preparations - human insulin, have time-action profiles that cannot fully imitate endogenous insulin secretion, thus leading to postprandial hyperglicemia and high glycemic oscilations during the day. Rapid-acting analogues. Rapid acting analogues should have a time-action profile with onset of less than one hour, duration less than four hours, hypoglycemic potency equal or greater than that of human insulin, and similar effects in all patients. Two rapid action analouges, lispro and aspart are available. Basal insulin analogues. The ideal basal insulin should provide slow and constant absorption, long half-life that would provide once daily dosing (or every other day, and peakless effect. Insulin glargine led to solubility at pH 4 and to slow absorption in neutral pH environment. Insulin detemir is a soluble insulin analogue with neutral pH and affinity to bind to serum albumin, thus gaining prolonged action. Mitogenic influence. The mitogenic influence of insulin is due to the affinity to bind to IGF-1 receptors. Following two-year administration of glargine in mice and rats, systemic carcinogenic potential was not found, though there were reports of hepatocellular carcinomas, which are frequently found in these animals. Conclusion. In the last two decades, many trials have shown that unsatisfactory glycemic control leads to chronic complications in both types of diabetes. Using basal glucose level, postprandial glycemy and HbA1c as

  10. ()-Garner aldehyde derived Baylis-Hillman adduct: A potential substrate for the synthesis of D- phytosphinosine analogue

    Indian Academy of Sciences (India)

    Gulshan Kumar; Amanpreet Kaur; Vasundhara Singh

    2014-11-01

    A short, facile and efficient synthesis of D-lyxo-phytosphingosine analogue has been achieved. The key steps involved are the Baylis-Hillman reaction of (S)-Garner aldehyde with methyl acrylate to obtain the corresponding adduct as the potential substrate, to which was added decylmagnesium bromide to obtain the E-trisubstituted alkene followed by OsO4/NMO mediated dihydroxylation gave the desired D-lyxophytosphingosine analogue intermediate diol which on acid hydrolysis resulted in the formation of the target molecule in good yield.

  11. 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.

  12. Treatment of chronic hepatitis B with nucleos(t)ide analogues.

    Science.gov (United States)

    Ohishi, Waka; Chayama, Kazuaki

    2012-03-01

    Recently antiviral therapies for chronic hepatitis B using nucleos(t)ide analogues have become standard treatment modalities on the basis of several independent guidelines, starting with those of the American Association for the Study of Liver Diseases (AASLD) and other such organizations and bodies, including the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver (APASL), and the Japanese Ministry of Health, Labour and Welfare (MHLW)'s research team. The philosophies underlying such treatment strategies are considered basically equivalent. MHLW's guidelines define subjects for medical intervention to be cases measuring alanine aminotransferase (ALT) ≥31 IU/L, with serological hepatitis B virus (HBV) DNA level ≥5 log copies/mL for hepatitis B e antigen (HBeAg)-positive cases, and serological HBV DNA level ≥4 log copies/mL for HBeAg-negative cases. These Japanese guidelines advocate entecavir as the first-line treatment option for nucleos(t)ide-naïve patients, and combination treatment of lamivudine and adefovir as the basis of treatment for patients with lamivudine- and/or entecavir-resistant viruses. Of particular note for patients undergoing lamivudine treatment with persistent HBV DNA level HBcrAg) level or HBV DNA level are considered useful markers for the appearance of such drug-resistant viruses.

  13. 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...

  14. Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts

    DEFF Research Database (Denmark)

    Kupisiewicz, Katarzyna; Boissy, Patrice; Abdallah, Basem M;

    2010-01-01

    The plant phytoalexin resveratrol was previously demonstrated to inhibit the differentiation and bone resorbing activity of osteoclasts, to promote the formation of osteoblasts from mesenchymal precursors in cultures, and inhibit myeloma cell proliferation, when used at high concentrations....... In the current study, we screened five structurally modified resveratrol analogues for their ability to modify the differentiation of osteoclasts and osteoblasts and proliferation of myeloma cells. Compared to resveratrol, analogues showed an up to 5,000-fold increased potency to inhibit osteoclast...... differentiation. To a lesser extent, resveratrol analogues also promoted osteoblast maturation. However, they did not antagonize the proliferation of myeloma cells. The potency of the best-performing candidate in vitro was tested in vivo in an ovariectomy-induced model of osteoporosis, but an effect on bone loss...

  15. 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 studi......, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring....

  16. A hypersaline spring analogue in Manitoba, Canada for potential ancient spring deposits on Mars

    Science.gov (United States)

    Berard, Genevieve; Applin, Daniel; Cloutis, Edward; Stromberg, Jessica; Sharma, Raven; Mann, Paul; Grasby, Stephen; Bezys, Ruth; Horgan, Briony; Londry, Kathleen; Rice, Melissa; Last, Bill; Last, Fawn; Badiou, Pascal; Goldsborough, Gordon; Bell, James

    2013-06-01

    This study explores the possible applications of a spring complex, East German Creek (EGC), Manitoba, Canada, as a terrestrial analogue for similar environments on Mars. Potential ancient spring deposits have been identified by Allen and Oehler (Allen, C.C., Oehler, D.Z. [2008]. Astrobiology 8, 1093-1112) in Vernal Crater, Arabia Terra, as well as in the intercrater plains of Terra Sirenum by Wray et al. (Wray et al. [2011]. J. Geophys. Res., 116, 1-41). EGC can provide guidance in the search for fossil spring deposits on Mars by using comparative mineralogy to contrast mineral identification from field studies to that available from remote sensing instruments such as the CRISM instrument aboard the Mars Reconnaissance Orbiter. The formation processes of EGC are also useful for finding spring-like environments on Mars. A variety of techniques were employed (X-ray diffractometry, reflectance spectra, water chemistry analysis) to analyze mineralogical changes in spring water precipitates with distance from the main springs at EGC, which were compared with concentrations of dissolved species in outflow water. Biosignatures in outflow stream sediments as well as the effect of surficial Fe oxyhydroxide coatings on the detection of underlying carbonate absorption features have also been spectrally characterized. Halite is the main mineral precipitated at EGC, followed by gypsum, and calcite. The presence of gypsum is readily detected in surficial precipitate spectra while halite does not have a diagnostic spectral signature in the 0.35-2.5 μm region. An absorption feature indicative of chlorophyll a is present in stream sediment spectra from most sampling stations and on outwash plain sediments. Carbonates appear to be spectrally detectable through a coating of ferric minerals, such as goethite by a characteristic absorption band near 2.3 μm. We attempted to detect significant spectral changes over an area of potential spring features in Vernal Crater on Mars using

  17. Current Status of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases

    Directory of Open Access Journals (Sweden)

    Pawel Robak

    2009-03-01

    Full Text Available For the past few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and become available for either in vitro studies or clinical trials. Among them the class of antineoplastic drugs belonging to the purine nucleoside analogues group (PNAs plays an important role. Three of them: pentostatin (DCF, cladribine (2-CdA and fludarabine (FA were approved by Food and Drug Administration (FDA for the treatment of hematological malignancies. Recently three novel PNAs: clofarabine (CAFdA, nelarabine (ara-G and forodesine (immucillin H, BCX-1777 have been synthesized and introduced into preclinical studies and clinical trials. These agents seem to be useful mainly for the treatment of human T-cell proliferative disorders and they are currently undergoing clinical trials in lymphoid malignancies. However, there are also several studies suggesting the role of these drugs in B-cell malignancies. This review will summarize current knowledge concerning the mechanism of action, pharmacologic properties, clinical activity and toxicity of PNAs accepted for use in clinical practice, as well as new agents available for clinical trials.

  18. 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

  19. N-alkylated aminoacyl sulfamoyladenosines as potential inhibitors of aminoacylation reactions and microcin C analogues containing D-amino acids.

    Directory of Open Access Journals (Sweden)

    Gaston H Vondenhoff

    Full Text Available Microcin C analogues were recently envisaged as important compounds for the development of novel antibiotics. Two issues that may pose problems to these potential antibiotics are possible acquisition of resistance through acetylation and in vivo instability of the peptide chain. N-methylated aminoacyl sulfamoyladenosines were synthesized to investigate their potential as aminoacyl tRNA synthetase inhibitors and to establish whether these N-alkylated analogues would escape the natural inactivation mechanism via acetylation of the alpha amine. It was shown however, that these compounds are not able to effectively inhibit their respective aminoacyl tRNA synthetase. In addition, we showed that (D-aspartyl-sulfamoyladenosine (i.e. with a (D-configuration for the aspartyl moiety, is a potent inhibitor of aspartyl tRNA synthetase. However, we also showed that the inhibitory effect of (D- aspartyl-sulfamoyladenosine is relatively short-lasting. Microcin C analogues with (D-amino acids throughout from positions two to six proved inactive. They were shown to be resistant against metabolism by the different peptidases and therefore not able to release the active moiety. This observation could not be reversed by incorporation of (L-amino acids at position six, showing that none of the available peptidases exhibit endopeptidase activity.

  20. Urodynamic parameters and plasma LH/FSH in spayed Beagle bitches before and 8 weeks after GnRH depot analogue treatment.

    Science.gov (United States)

    Reichler, Iris Margaret; Barth, Andrea; Piché, Claude A; Jöchle, Wolfgang; Roos, Malgorzata; Hubler, Madeleine; Arnold, Susi

    2006-12-01

    The pathophysiology of urinary incontinence due to spaying remains unknown. Incontinent bitches can be treated successfully with depot preparations of GnRH-analogues and there are differences in plasma gonadotropin levels between continent and incontinent spayed bitches. It is therefore assumed that the supraordinated hormones, GnRH, FSH, and/or LH, have an effect on the urodynamic parameters. In this study, the potential influence of these hormones on the lower urinary tract was investigated by measuring urethral pressure profiles and cystometry. Simultaneously, plasma concentrations in 10 spayed Beagle bitches were determined 5 weeks prior to and 8 weeks after treatment with the GnRH analogue leuprolide. Within 1 week of GnRH analogue administration, plasma FSH and LH levels decreased from 72.5 and 7.7 to 7.75 and 0.72ng/mL, respectively. These plasma gonadotropin levels correspond with those of intact bitches during anoestrus. Urethral pressure profiles indicated that the treatment had no significant effect on maximum urethral closure pressure, functional and total length of the urethra, or area of the closure pressure curve. The data obtained by cystometry regarding mean bladder threshold volume showed a significant increase from 109 to 172mL. The improvement in bladder function after the application of GnRH-application is presumably a direct effect of the GnRH as a relationship between the plasma gonadotropin levels and the urodynamic parameters could not demonstrated. PMID:16876857

  1. 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. PMID:25778708

  2. Squalamine analogues as potential anti-trypanosomal and anti-leishmanial compounds.

    Science.gov (United States)

    Khabnadideh, S; Tan, C L; Croft, S L; Kendrick, H; Yardley, V; Gilbert, I H

    2000-06-01

    This paper concerns the synthesis of various simplified analogues of the novel anti-microbial agent, squalamine. The compounds were then investigated for activity against Trypanosoma brucei, the causative agent of African trypanosomiasis, Trypanosoma cruzi, the causative agent of Chagas disease and Leishmania donovani, the causative agent of visceral leishmaniasis. Several compounds showed in vitro activity, especially against T. brucei and L. donovani. However, one compound showed poor in vivo activity. PMID:10866389

  3. 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.

  4. The potential use of natural analogue studies in radioactive waste disposal: a review

    International Nuclear Information System (INIS)

    Radioactive waste must be disposed of in such a way that it remains safe for periods of time which are often well beyond our ability to guarantee control and surveillance. The performance of the repository cannot, of course, be demonstrated practically nor by experiment because of the long time scales involved. Model predictions should be valid for thousands of years and, in the case of very long-lived radionuclides, even hundreds of thousands of years. Consequently, safety analysts over the past 10 years have recognised that the study of natural systems (or natural analogues) provides opportunities to test, by observation and measurement, many of the geochemical processes that are expected to influence the predicted reliability of radioactive waste containment over realistically long periods of geological time. In addition to the time scale factor, these analogue studies attempt to understand the multiprocess complexity of the natural system by an interdisciplinary approach, which contrasts with the limitations of the laboratory. This paper reviews the application of natural analogue studies to demonstrate the safety of deep radioactive waste disposal; emphasis has been put on the Swedish disposal concept as an example. Examples of such applications are described and finally the main performance assessment objectives are discussed. Future areas of improvement are also addressed. (authors). 69 refs., 4 figs., 1 tab

  5. Methods to assess the biodistribution of radiolabelled somatostatin analogues and treatment response of neuroendocrine tumours

    Science.gov (United States)

    Gnanasegaran, Gopinath

    Introduction: During the past decade, proof of the principle that somatostatin receptors can be successfully used for in vivo targeting of neuroendocrine tumours (NETs) has been provided. These tumours are imaged with 111Indium-pentetreotide and treated with 90Yttrium labeled somatostatin analogues. The aim of this study was to assess (a) the biodistribution and residency of 90Y labelled agents using the brehmsstrahlung imaging technique (b) the tumour response to various treatment modalities using a simplified scintigraphic method [Functional SPECT tumour volume (STV)]. Material and methods: 1) 19 patients with NETs were imaged with 111In-pentetreotide and 14 of them underwent treatment with 90Y-lanreotide. The rest underwent treatment with 90Y-SMT. All the patients were imaged 24 hours post-therapy. Brehmsstrahlung images obtained post therapies were used to assess the 90Y-lanreotide biodistribution in 14 patients and the 5 patients treated with 90Y-SMT, comparing them with 111In-pentetreotide. 2) In 42 patients with NETs a retrospective analysis was performed of the 111In-pentetreotide imaging and CT scan in patients treated with different therapies. A simplified scintigraphic method using 111In-pentetreotide SPECT liver imaging was used to monitor changes in tumour response and to determine how this correlates with CT scan and clinical response. Results: 1) 90Y-lanreotide and 90Y-SMT (with amino acids) have much lower uptake in the kidney (p 0.000 and 0.041 respectively) than 111In-pentetreotide. G Gnanasegaran MD 2 2) 22/42 patients had a good clinical response. A mean fall in total functional STV of 37% was seen in patients with symptomatic relief and a mean increase of 72 % was seen in patients with no symptomatic relief STV predicted the clinical outcome in 34 patients (81%) and CT predicted the outcome in 21 (50%) patients. Conclusion: There was a difference in biodistribution between 111In-pentetreotide and 90Y-lanreotide/ 90Y-SMT, especially in the

  6. Attitudes and preferences in patients with acromegaly on long-term treatment with somatostatin analogues

    Directory of Open Access Journals (Sweden)

    Cecilia Follin

    2016-08-01

    Full Text Available Introduction: Patients with acromegaly can be treated with surgery, medical therapy and/or radiation therapy. For the patients not being cured with surgery, treatment with somatostatin analogues (SSAs is the primary therapy. SSA can be taken by self- or partner-administered injections in addition to being given by a nurse at a clinic. The aim was to assess if patients with acromegaly prefer self-injections and to investigate their attitudes towards long-term medical therapy. Method: All patients in the southern medical region of Sweden with a diagnosis of acromegaly and treated with SSA were eligible for the study (n = 24. The study is based on a questionnaire asking about the patients’ attitudes and preferences for injections with SSA, including their attitudes towards self-injection with SSA. Results: The patients’ (23 included median age was 68.5 years and the patients had been treated with SSA for 13 (1–38 years. One patient was currently self-injecting. All of the other patients were receiving injections from a nurse at a clinic. Three patients preferred self-injections, one preferred partner injections and 19 patients did not prefer self- or partner injections. The most frequent arguments to not preferring self-injections were ‘feeling more secure with an educated nurse’ and ‘preferring regular contact with a specialised nurse’. Conclusion: Patients with acromegaly prefer regular contact with the endocrine team to the independence offered by self-injections. These findings might mirror the patients’ desires for continuity and safety. We need to address patients’ concerns regarding injections with SSA and support them in their choices.

  7. Climate analogues suggest limited potential for intensification of production on current croplands under climate change.

    Science.gov (United States)

    Pugh, T A M; Müller, 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. PMID:27646707

  8. Design, synthesis and biological evaluation of new rhodacyanine analogues as potential antitumor agents

    Institute of Scientific and Technical Information of China (English)

    Yang Xiong Li; Xin Zhai; Wei Ke Liao; Wu Fu Zhu; Ying He; Ping Gong

    2012-01-01

    In an attempt to develop potent antitumor agents,new rhodacyanine analogues containing the pyridinium ring (5a-5h),the isoquinolinium ring (6a-6c) and the quinolinium ring (7a-7e) linked to the rhodanine ring via N-N covalent bond were designed,synthesized and evaluated for antitumor activity against human lung cancer cell line (H460) by MTT assay in vitro.Most of the tested compounds showed enhanced antitumor activity with IC50 values ranging from 0.006 to 9.2 μmol/L as compared to the lead compound MKT-077.Among them,the most promising compound 7d (IC50 =0.006 μmol/L) was 216.7 times more active than MKT-077 (IC50 =1.3 μmol/L).The preliminary structure-activity relationship of the target compounds was discussed.

  9. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

    International Nuclear Information System (INIS)

    Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29±0.11). The size ratio for the hypointense tumors was 0.82±0.14, and 0.82±0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

  10. 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. PMID:26785848

  11. Prostaglandins and its analogues : An approach for treatment of anoestrus and to enhance breeding efficiency

    Directory of Open Access Journals (Sweden)

    G B Dudhatra

    2012-12-01

    Full Text Available Cloprostenol is a synthetic prostaglandin F analogue. It is a FP (Prostaglandin F receptor agonist, which shows 2á powerful luteolytic effects. It also stimulates the contraction of uterine and bronchial smooth muscle and produces vasoconstriction in some vessels. Anoestrous may be due to some conditions like abnormal pregnancy, early pregnancy, pyometra, endometritis, retention of placenta, maceration and mummification. So, get rid of this conditions cloprostenol is widely used. It has been now in vogue to administer PGF or its analogue in early 2á postpartum cows and buffaloes in order to hasten early resumption of cyclic ovarian activity and thereby to increase the reproductive efficiency. To improve reproductive efficiency, it is necessary to inseminate cows early in the breeding season so that, thereby achieving a more compact calving season. Breeding efficiency is increased by means of synchronization of estrus, conception rate and pregnancy rate. Estrus synchronization can be achieved by lysis of corpus luteum by administration of prostaglandin (PGF or its synthetic analogue on 5-17 2á days of the estrus cycle. The cows will return to estrus within 3-5 days. The effective therapeutic doses for cloprostenol are 500 μg in cattle and 175 μg in pigs. However, for R-cloprostenol, the recommended doses are: 150 μg in cattle and 75 μg in pigs. In both cases, it is administered by the intramuscular route. [Vet. World 2012; 5(6.000: 378-384

  12. Suramin analogues with a 2-phenylbenzimidazole moiety as partial structure; potential anti HIV- and angiostatic drugs, 2: Sulfanilic acid-, benzenedisulfonic acid-, and naphthalenetrisulfonic acid analogues.

    Science.gov (United States)

    Kreimeyer, A; Müller, G; Kassack, M; Nickel, P; Gagliardi, A R

    1998-03-01

    The synthesis of suramin analogues bearing a 2-phenyl-benzimidazole moiety is described. Aminoarene sulfonic acids 2a-e are acylated with 3,4-dinitrobenzoyl chloride 3 yielding the amides 4a-e which are hydrogenated to the corresponding diamines 5a-e. These are treated with 3-nitrobenzaldehyde, yielding the azomethines 7a-e and their isomers 8a-e and 9a-e. Key step in the synthesis of the target compounds 12a-e is the oxidation of the azomethines with oxygen to the benzimidazoles 10a-e. These are hydrogenated to the amines 11a-e reacting with phosgene to yield the symmetric ureas 12a-e. Results of the anti-HIV, cytostatic, and antiangiogenic screening are presented.

  13. Redox potential tuning by redox-inactive cations in nature's water oxidizing catalyst and synthetic analogues.

    Science.gov (United States)

    Krewald, Vera; Neese, Frank; Pantazis, Dimitrios A

    2016-04-28

    The redox potential of synthetic oligonuclear transition metal complexes has been shown to correlate with the Lewis acidity of a redox-inactive cation connected to the redox-active transition metals of the cluster via oxo or hydroxo bridges. Such heterometallic clusters are important cofactors in many metalloenzymes, where it is speculated that the redox-inactive constituent ion of the cluster serves to optimize its redox potential for electron transfer or catalysis. A principal example is the oxygen-evolving complex in photosystem II of natural photosynthesis, a Mn4CaO5 cofactor that oxidizes water into dioxygen, protons and electrons. Calcium is critical for catalytic function, but its precise role is not yet established. In analogy to synthetic complexes it has been suggested that Ca(2+) fine-tunes the redox potential of the manganese cluster. Here we evaluate this hypothesis by computing the relative redox potentials of substituted derivatives of the oxygen-evolving complex with the cations Sr(2+), Gd(3+), Cd(2+), Zn(2+), Mg(2+), Sc(3+), Na(+) and Y(3+) for two sequential transitions of its catalytic cycle. The theoretical approach is validated with a series of experimentally well-characterized Mn3AO4 cubane complexes that are structural mimics of the enzymatic cluster. Our results reproduce perfectly the experimentally observed correlation between the redox potential and the Lewis acidities of redox-inactive cations for the synthetic complexes. However, it is conclusively demonstrated that this correlation does not hold for the oxygen evolving complex. In the enzyme the redox potential of the cluster only responds to the charge of the redox-inactive cations and remains otherwise insensitive to their precise identity, precluding redox-tuning of the metal cluster as a primary role for Ca(2+) in biological water oxidation.

  14. Evaluation of technetium-99m/rhenium labelled nucleoside analogues as potential radiotracers in oncology

    International Nuclear Information System (INIS)

    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-[18F]fluoro-3-(hydroxymethyl)butyl]guanine [18F]FHBG) or [124I]iodo-2'-fluoro-2'-deoxy-l-β-D-arabino-furanosyluracil (124I]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 (t1/2 = 6.02 h; Eγ = 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 (∼ 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 [ReBr3(CO)3]2- and [99mTc(OH2)3(CO)3]+ 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 Kiu values ranging from 4.4-334 μM. 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 (Ki = 16.3 ± 4.6 μM). This compound also exhibited a mixed inhibition of the hTK1 with Kic = 73 ± 20 μM. When tested in vitro for cell uptake in transfected

  15. Total synthesis of furospongolide and related furanolipid analogues as potential anti-tumour agents

    OpenAIRE

    Harrold, Donal Patrick

    2014-01-01

    This thesis details the design, development and execution of innovative methodology in the total synthesis of the terpene-derived marine natural product, furospongolide. It also outlines the synthetic routes used to prepare a novel range of furanolipids derivatives and subsequent evaluation of their potential as antitumour agents. The first chapter is a review of the literature describing efforts undertaken towards the synthesis of biologically active furanosesterterpenoid marine natural prod...

  16. Second-Harmonic Generation Imaging of Membrane Potential with Retinal Analogues

    OpenAIRE

    Theer, Patrick; Denk, Winfried; Sheves, Mordechai; Lewis, Aaron; Detwiler, Peter B.

    2011-01-01

    Second-harmonic generation (SHG) by membrane-incorporated probes is a nonlinear optical signal that is voltage-sensitive and the basis of a sensitive method for imaging membrane potential. The voltage dependence of SHG by four different probes, three retinoids (all-trans retinal), and two new retinal analogs, 3-methyl-7-(4′-dimethylamino-phenyl)-2,4,6-heptatrienal (AR-3) and 3,7-dimethyl-9-(4′-dimethylamino-phenyl)-2,4,6,8-nonatetraenal (AR-4), and a styryl dye (FM4-64), were compared in HEK-...

  17. Can a new ultra-long-acting insulin analogue improve patient care? Investigating the potential role of insulin degludec.

    Science.gov (United States)

    Robinson, Jennifer D; Neumiller, Joshua J; Campbell, R Keith

    2012-12-24

    The basal-bolus concept of delivering insulin to diabetic patients makes physiological sense, as it mimics normal insulin release in people without diabetes. In line with this concept, a major effort put forth by insulin manufacturers has been to develop the ideal exogenous basal insulin product. The perfect basal insulin product would be injected into subcutaneous tissue without causing irritation, release insulin continuously at a constant rate for at least 24 hours, be stable, not contribute to weight gain, have a low risk of allergic reactions and, very importantly, minimize the risk of hypoglycaemia. While the perfect insulin has not yet been discovered, advancements are still being made. Insulin degludec is an ultra-long-acting basal insulin analogue that possesses a flat, stable glucose-lowering effect in patients with type 1 or type 2 diabetes mellitus. Insulin degludec achieves these pharmacokinetic properties by forming soluble multihexamers upon subcutaneous injection, resulting in the formation of a depot in the subcutaneous tissue that is slowly released and absorbed into circulation. Insulin degludec has been associated with slightly less weight gain and fewer nocturnal hypoglycaemic episodes when compared with insulin glargine in some, but not all, clinical studies. This article briefly reviews current evidence for the use of insulin degludec in patients with type 1 or type 2 diabetes mellitus and discusses the potential impact of this new basal insulin on clinical practice. PMID:23145524

  18. 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

  19. 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.

  20. Radiolabeled somatostatin analogues

    International Nuclear Information System (INIS)

    Somatostatin is a naturally occurring tetradecapeptide that inhibits the secretion of many hormones. Large numbers of binding sites with high affinity for somatostatin have been reported in a variety of tumors. An octapeptide analogue of somatostatin, octreotide (Sandostatin), is currently used in the treatment of patients with somatostatin receptor-positive tumors to limit hormonal hyper secretion. In an effort to utilize the high specificity of octreotide for scintigraphic imaging of somatostatin receptor-positive tumors, a tyrosine derivative of octreotide was prepared and labeled with the radioactive isotope, I-123. While the early clinical results obtained with this radiopharmaceutical were encouraging, the I-123 labeling procedure proved cumbersome and variable. To circumvent these difficulties, researchers at University Hospital Rotterdam (Holland) and Sandoz Research Institute (Switzerland) developed an In-111 labeled analogue of octreotide. This radiopharmaceutical is easy to prepare and has proven to be even more effective than the I-123 derivative in the scintigraphic imaging of tumors. These radiopharmaceutical developments and clinical observations are discussed in light of their relevance to the generation of new radiolabeled peptides for the diagnosis and potential radiotherapy of cancer. (authors). 30 refs., 5 figs

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

    International Nuclear Information System (INIS)

    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)

  2. 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.

  3. 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...

  4. Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors.

    Science.gov (United States)

    Jarończyk, Małgorzata; Wołosewicz, Karol; Gabrielsen, Mari; Nowak, Gabriel; Kufareva, Irina; Mazurek, Aleksander P; Ravna, Aina W; Abagyan, Ruben; Bojarski, Andrzej J; Sylte, Ingebrigt; Chilmonczyk, Zdzisław

    2012-03-01

    It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D docking). The crystal structures of leucine transporter from Aquifex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro- and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators. PMID:22309909

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

    International Nuclear Information System (INIS)

    Many of the processes which will lead to the breakdown of engineered barriers and the mobilisation 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. Existing studies are assessed and possibilities considered for additional analogues. 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 considerable amount of the information reviewed and presented could be used in the assessment of disposal of other waste types in other host rocks. (Auth.)

  6. 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....

  7. Current status of thiopurine analogues in the treatment in Crohn's disease

    OpenAIRE

    Lakatos, Peter Laszlo; Kiss, Lajos S

    2011-01-01

    In the last decades, with the development of biological therapy, the treatment paradigms in patients with Crohn’s disease have continuously evolved. Several studies focusing on the optimal use of both traditional immunosuppressants and biological therapy have been published, investigating conventional, accelerated step-up and top-down approaches. In addition, much emphasis has been placed in recent years on the determination of important predictive factors that could enable early patient stra...

  8. 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.

  9. 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.

  10. Current status of thiopurine analogues in the treatment in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos; Lajos S Kiss

    2011-01-01

    In the last decades, with the development of biological therapy, the treatment paradigms in patients with Crohn's disease have continuously evolved. Several studies focusing on the optimal use of both traditional immunosuppressants and biological therapy have been published, investigating conventional, accelerated step-up and top-down approaches. In addition, much emphasis has been placed in recent years on the determination of important predictive factors that could enable early patient stratification, which would lead to a tailored management strategy. In this review, the authors try to highlight new evidence on the optimal timing, benefits, and risks of immunosuppressants alone, or in combination, in patients with Crohn's disease.

  11. Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment.

    Science.gov (United States)

    Jordan, Brian C; Mock, Charlotta D; Thilagavathi, Ramasamy; Selvam, Chelliah

    2016-05-01

    Primary prostate cancer, also known as prostate adenocarcinoma (PCa), is a devastating cancer in men worldwide. Europe and developing countries of Asia have fewer reported cases of prostate cancer compared to increasing cases in the United States with higher incidence in Black men. Risk factors associated with prostate cancer are aging, genetics, lifestyle, high body mass index as well as carcinogenic exposure to carbon-containing fuels, tobacco, and charbroiled meats. Hormone therapy and radical prostatectomy are commonly implemented treatments. The >20.000 prostate cancer deaths of 2013 suggest that there exists a need for enhanced chemopreventive and therapeutic agents for prostate cancer treatment. Fruits, vegetables, and red wines contain high levels of polyphenolic levels. Consumption of these products may provide chemoprevetion of PCa. Curcumin, the major compound from the turmeric rhizome Curcuma longa has long been used for medicinal purposes as an antiseptic and wound healing. This review focuses on curcumin's therapeutic effectiveness in vitro and in vivo in prostate cancer models. The review will highlight the mechanisms of actions of curcumin in the signaling pathways of prostate cancer. PMID:27018446

  12. Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide.

    Science.gov (United States)

    Page, M D; Millward, M E; Taylor, A; Preece, M; Hourihan, M; Hall, R; Scanlon, M F

    1990-02-01

    We have treated 16 acromegalic patients for up to 44 months with octreotide in varying doses. Growth hormone levels were suppressed in 14 patients with associated clinical improvement. IGF-1 levels were measured in 12 and fell into the normal range in 10. Prolactin was suppressed in six hyperprolactinaemic patients but was unaltered in normoprolactinaemic acromegalic patients. Post-prandial hyperglycaemia with impaired insulin secretion was noted in all patients, and one patient required oral hypoglycaemic agents. Octreotide did not affect thyroid function. CT scans from before and after six months of treatment demonstrated minimal tumour shrinkage in only two patients. Octreotide was well tolerated with no serious haematological or biochemical disturbance and no evidence of malabsorption. Two patients developed gallstones. Octreotide is effective in acromegaly. The development of gallstones is the only serious adverse event we have encountered.

  13. Biological and quantitative-SAR evaluations, and docking studies of (E)-N -benzylidenebenzohydrazide analogues as potential antibacterial agents.

    Science.gov (United States)

    Alam, Mohammad Sayed; Jebin, Sefat; Rahman, M Mostafizur; Bari, Md Latiful; Lee, Dong-Ung

    2016-01-01

    A series of 15 (E)-N'-benzylidenebenzohydrazide analogues were evaluated for their antimicrobial activities against eleven pathogenic and food-borne microbes, namely, S. aureus (G(+)), L. monocytogenes (G(+)), B. subtilis (G(+)), K. pneumonia (G¯), C. sakazakii (G¯), C. freundii (G¯), S. enterica (G¯), S. enteritidis (G¯), E. coli (G¯), Y. pestis (G¯), and P. aeruginosa (G¯). Most of the compounds exhibited selective activity against some Gram-negative bacterial strains. Of the compounds tested (3a-o), 3b and 3g were most active against C. freundii (MIC = ~19 µg mL(-1)). Whereas, compounds 3d, 3i, 3k and 3n exhibited MIC values ranging from 37.5 to 75 μg mL(-1) against C. freundii, and compounds 3e, 3l and 3n had MIC values of ~75 μg mL(-1) against K. pneumonia. Quantitative structure-antibacterial activity relationships were studied using physicochemical parameters and a good correlation was found between calculated octanol-water partition coefficients (clogP; a lipophilic parameter) and antibacterial activities. In silico screening was also performed by docking high (3b and 3g) and low (3n) activity compounds on the active site of E. coli FabH receptor, which is an important therapeutic target. The findings of these in silico screening studies provide a theoretical basis for the design and synthesis of novel benzylidenebenzohydrazide analogues that inhibit bacterial FabH. PMID:27540348

  14. Analogue mouse pointer control via an online steady state visual evoked potential (SSVEP) brain-computer interface

    Science.gov (United States)

    Wilson, John J.; Palaniappan, Ramaswamy

    2011-04-01

    The steady state visual evoked protocol has recently become a popular paradigm in brain-computer interface (BCI) applications. Typically (regardless of function) these applications offer the user a binary selection of targets that perform correspondingly discrete actions. Such discrete control systems are appropriate for applications that are inherently isolated in nature, such as selecting numbers from a keypad to be dialled or letters from an alphabet to be spelled. However motivation exists for users to employ proportional control methods in intrinsically analogue tasks such as the movement of a mouse pointer. This paper introduces an online BCI in which control of a mouse pointer is directly proportional to a user's intent. Performance is measured over a series of pointer movement tasks and compared to the traditional discrete output approach. Analogue control allowed subjects to move the pointer faster to the cued target location compared to discrete output but suffers more undesired movements overall. Best performance is achieved when combining the threshold to movement of traditional discrete techniques with the range of movement offered by proportional control.

  15. Decreased keratocyte density and central corneal thickness in primary open-angle glaucoma patients undergoing treatment with topical prostaglandin analogues

    Directory of Open Access Journals (Sweden)

    Sibel Kocabeyoglu

    2015-01-01

    Full Text Available Purpose: To evaluate whether prostaglandin (PG analogue use is associated with alterations in keratocyte density and central corneal thickness (CCT in subjects with primary open-angle glaucoma (POAG. Materials and Methods: Thirty-five POAG patients treated with PG analogues for >2 years and 35 control subjects without glaucoma were included in this cross-sectional study. All subjects were underwent CCT measurements using ultrasound pachymetry. Keratocyte densities of each stromal layer were determined by in vivo confocal microscopy. Student′s t-test and Chi-square test were used for statistical evaluations. Correlations between keratocyte densities and CCT were analyzed using Pearson′s correlation analysis. Results: Keratocyte densities in each stromal layer were significantly lower in glaucoma patients receiving PG analogues as compared to those of controls (P < 0.001. The mean CCT was also lower in glaucoma patients (515.2 ± 18.8 μ than control subjects (549.6 ± 21.1 μ, P < 0.001. A positive correlation between keratocyte densities in each stromal layer and CCT was observed in POAG patients. Conclusions: Long-term administration of topical PG analogues may adversely influence keratocyte densities and CCT. Further prospective studies are required clarify the relationship between PG analogues and their effects on the cornea.

  16. 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.

  17. Exploring the effect of N-substitution in nor-lobelane on the interaction with VMAT2: discovery of a potential clinical candidate for treatment of methamphetamine abuse.

    Science.gov (United States)

    Zheng, Guangrong; Horton, David B; Penthala, Narsimha Reddy; Nickell, Justin R; Culver, John P; Deaciuc, Agripina G; Dwoskin, Linda P; Crooks, Peter A

    2013-03-01

    A series of N-substituted lobelane analogues was synthesized and evaluated for their [(3)H]dihydrotetrabenazine binding affinity at the vesicular monoamine transporter and for their inhibition of vesicular [(3)H]dopamine uptake. Compound 19a, which contains an N-1,2(R)-dihydroxypropyl group, had been identified as a potential clinical candidate for the treatment of methamphetamine abuse.

  18. 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

    : 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...... to a limited number of reported estimates, a meta-analysis was performed for glargine only. A comprehensive overview was composed for in vitro and animal studies. Protein and gene expression was analysed for the cell lines most frequently used in the included in vitro studies. RESULTS: In total 16 in vitro, 5...... animal, 2 in vivo human and 29 epidemiological papers were included. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. However...

  19. Intravenous prostacyclin analogue iloprost (Ilomedin® in the treatment of a patient with Buerger’s disease

    Directory of Open Access Journals (Sweden)

    Ilshat Ravilevich Gaisin

    2013-01-01

    Full Text Available Buerger’s disease, or thromboangiitis obliterans, is a severe disabling systemic disease of vessels. The paper describes a case of thromboangiitis obliterans in a patient with three extremities amputated during vascular therapy. The course intravenous administration of the stable prostacyclin analogue iloprost (Ilomedin® allows the only extremity to be preserved.

  20. 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.

  1. NATURAL ANALOGUE SYNTHESIS REPORT

    International Nuclear Information System (INIS)

    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

  2. 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. PMID:26974371

  3. Role of premixed insulin analogues in the treatment of patients with type 2 diabetes mellitus: A narrative review

    OpenAIRE

    Elizarova, Svetlana; Galstyan, Gagik R; Wolffenbuttel, Bruce HR

    2014-01-01

    Because of the progressive nature of type 2 diabetes mellitus (T2DM), insulin therapy will eventually become necessary in most patients. Recent evidence suggests that maintaining optimal glycemic control by early insulin therapy can reduce the risk of microvascular and macrovascular complications in patients with T2DM. The present review focuses on relevant clinical evidence supporting the use of premixed insulin analogues in T2DM when intensifying therapy, and as starter insulins in insulin-...

  4. Monochromatic excimer light versus combination of topical steroid with vitamin D3 analogue in the treatment of nonsegmental vitiligo: a randomized blinded comparative study.

    Science.gov (United States)

    Abdel Latif, Azmy Ahmed; Ibrahim, Shady Mahmoud Attia

    2015-01-01

    Vitiligo is a difficult disease to treat, socially stigmatizing its patients. Monochromatic excimer light (MEL) was developed for use in dermatology and adapted for the treatment of vitiligo. Comparing the efficacy of MEL versus topical combination therapy of vitamin D3 analogue and steroid in the treatment of nonsegmental vitiligo. Forty-four patients with localized and stable nonsegmental vitiligo participated in the present study. In each patient, two lesions were selected and divided randomly into two groups, group A was treated with daily topical combination of calcipotriol and betamethasone and group B was treated with biweekly sessions of MEL for 3 months. Efficacy based on repigmentation percentages were blindly evaluated by two independent physicians and patient's satisfaction. There was significant improvement in both treatment modalities at the end of the study, but without significant differences in both groups. There was a significant difference between both groups regarding the onset of repigmentation (p-value vitiligo.

  5. Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    International Nuclear Information System (INIS)

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe1-Tyr3-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T1/2 =9.5 hr; β+=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67Ga- and 68Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPETTM images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0±0.7, 13.2±2.1 and 9.8±1.5 for 66Ga-, 67Ga-, and 68Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio 1.64), and high kidney uptake must be eliminated

  6. 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...

  7. [Contemporary potential of nonmedical treatment in ophthalmology].

    Science.gov (United States)

    Drakon, A K; Elfimov, M A; Illarionov, V E; Ivanova, I I; Portnov, V V

    2016-01-01

    The article covers treatment results of 90 patients with primary glaucoma simplex of stage 1 and 2 (137 eyes). The authors proved that using a specified magnetotherapy method, when compared to regular medical therapy, causes more fast and marked regression in clinical symptoms and improvement of vision in patients with primary glaucoma simplex of stages 1 and 2. PMID:27164744

  8. Photochemical Wastewater Treatment for Potential Agricultural Use

    Directory of Open Access Journals (Sweden)

    Sandra García

    2014-12-01

    Full Text Available The urban wastewaters after advanced primary treatment (APT are again discharged into the river without any use. In the present research in a soilless culture system where maize seedlings were tested three different treatments were planted: 1. Obtained from the effluent water of an APT, 2. Photochemically treated wastewater (PCT and 3. Urban water network (UW. A block randomly distributed design was tested, with five repetitions where the experimental unit was formed by a 36 cavities filled with Peat Moss and the useful plot was considered by 16 central plants for each experimental unit. Irrigations were scheduled since the first time of the planting, employed 27 mL/cavity. The removal of the organic contaminants present into the water was conducted by the employment of a Batch photoreactor, adapted with a recirculation system (UV/H2O2/O3, evaluated to determine UV-Vis spectra, pH, color and turbidity parameters initial and final samples. Measurements of height and percentage of germination in plants, where is determined that the seedlings irrigated with water PCT were reached the highest average compared to APT and UW irrigated; After the 50 cm growing plant, a determination of the presence of heavy metal, via atomic absorption method, were carried on analyzing the leaves, roots and stalks of the samples. Concluding that the presences of heavy metals into the APT were higher than PCT treatments, it can be an impediment for the normal growing of the plants. Therefore, the application of the photochemical treatment using (UV/H2O2/O3 system, represent a viable alternative for the wastewater treatment after the APT process to possible use of irrigation.

  9. Lithofacies and spectral gamma-ray analysis of a potential outcrop analogue for a secondary reservoir in the McCully Gas Field, Sussex, NB

    Energy Technology Data Exchange (ETDEWEB)

    Keighley, D.; Mohan, D. [New Brunswick Univ., Fredericton, NB (Canada). Dept. of Geology

    2006-07-01

    The McCully Gas Field in New Brunswick, comprises a succession of gas-filled sandstone units with organic shale. Core data from the reservoir interval in the gas field indicates that the sandstones are the deposits of lacustrine deltas, shorelines and fluvial systems. This study attempted to provide a more detailed interpretation of the lithofacies and sequence stratigraphy of outcrops and to better correlate the outcrops with producing horizons in the subsurface. The primary producing horizon in the McCully field is the A-sand, for which an equivalent outcrop analogue has yet to be identified. Overlying secondary targets include sandstone packages that appear to coarsen upward over a scale of several tens of metres. An outcrop of a coarsening upward succession within a roadcut has been identified as potentially correlative. Detailed sedimentological logging and spectral gamma ray data was collected over a 40 m thick interval of the outcrop succession. It appears that sedimentation occurred in a periodically and progressively shallowing wave-dominated lake shoreface. A possible root horizon near the top of the succession could indicate a temporary lowering of lake-level and development of a shallow lagoon. An overlying limestone conglomerate was identified as a storm-beach deposit. Conclusive evidence of fluvial deposition within the succession was not found. Spectral gamma-ray data suggests that radioactive uranium and thorium, as well as potassium all decrease upsection together with an overall increase in grain size.

  10. 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

  11. Occurrence and profiles of bisphenol analogues in municipal sewage sludge in China.

    Science.gov (United States)

    Song, Shanjun; Song, Maoyong; Zeng, Luzhe; Wang, Thanh; Liu, Runzeng; Ruan, Ting; Jiang, Guibin

    2014-03-01

    Extensive use of bisphenol A and its analogues has caused increasing concern over the potential adverse health impacts of these chemicals. In this study, the presence and profiles of 13 bisphenols (BPs) were investigated in 52 municipal sewage sludge samples collected from 30 cities in China. Tetrabromobisphenol A was the most frequently observed analogue (geometric mean: 20.5 ng/g dw). Bisphenol A (4.69 ng/g dw), bisphenol S (3.02 ng/g dw), and bisphenol F (3.84 ng/g dw) were found with similar frequency. Other BP analogues such as tetrachlorobisphenol A, bisphenol AF, bisphenol E, and dihydroxybiphenyl were identified for the first time in sewage sludge in China. Significant correlations were found among BP concentrations, but no relationships were found with wastewater treatment plant characteristics. Profiles of the relative estradiol equivalents suggested that the estrogenic potential of BP mixtures may be associated with the occurrence and contributions of specific analogues.

  12. 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

  13. Separation of Variable Treatment for Solving Time—Dependent Potentials

    Institute of Scientific and Technical Information of China (English)

    QIANShang-Wu; GUZhi-Yu; 等

    2001-01-01

    We use the separation of variable treatment to treat some time-dependent systems,and point out that the condition of separability is the same as the condition of existence of invariant,and the separation of variable treatment is interrelated with the quantum-invariant method and the propagator method.We directly use the separation of variable treatment to obtain the wavefunctions of the time-dependent Coulomb potential and the time-dependent Hulthen potential.

  14. 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......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...

  15. 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

  16. 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 gro

  17. 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.

  18. 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.

  19. Separation of Variable Treatment for Solving Time-Dependent Potentials

    Institute of Scientific and Technical Information of China (English)

    QIAN Shang-Wu; GU Zhi-Yu; XIE Guo-Qiang

    2001-01-01

    We use the separation of variable treatment to treat some time-dependent systems, and point out that the condition of separability is the same as the condition of existence of invariant, and the separation of variable treatment is interrelated with the quantum-invariant method and the propagator method. We directly use the separation of potential.

  20. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    Science.gov (United States)

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  1. Bacteriophages-potential for application in wastewater treatment processes

    Energy Technology Data Exchange (ETDEWEB)

    Withey, S. [School of Water Sciences, Cranfield University, Cranfield, Bedfordshire, MK43 0AL (United Kingdom); Cartmell, E. [School of Water Sciences, Cranfield University, Cranfield, Bedfordshire, MK43 0AL (United Kingdom)]. E-mail: e.cartmell@cranfield.ac.uk; Avery, L.M. [School of Water Sciences, Cranfield University, Cranfield, Bedfordshire, MK43 0AL (United Kingdom); Stephenson, T. [School of Water Sciences, Cranfield University, Cranfield, Bedfordshire, MK43 0AL (United Kingdom)

    2005-03-01

    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.

  2. 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.

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

    Science.gov (United States)

    Lunagariya, Jignesh; Zhong, Shenghui; Chen, Jianwei; Bai, Defa; Bhadja, Poonam; Long, Weili; Liao, Xiaojian; Tang, Xiaoli; Xu, Shihai

    2016-01-01

    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. PMID:27598177

  4. 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.

  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. 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.)

  7. Predication of Fhhh potential in PTA wastewater treatment

    Institute of Scientific and Technical Information of China (English)

    CHENG Shu-pei; SHI Lei; ZHANG Xu-xiang; YAN Jun; DING Zhong-hai; HAO Chun-bo

    2004-01-01

    Ebis is the intelligent environmental biotechnological informatics software developed for judging the effectiveness of the microorganism strain in the industrial wastewater treatment system(IWTS) at the optimal status. The parameter, as the objective function for the judgment, is the minimum reactor volume ( Vmin ) calculated by Ebis for microorganism required in wastewater treatment. The rationality and the universality of Ebis were demonstrated in the domestic sewage treatment system(DSTS) with the data published in USA and China at first, then Fhhh strain's potential for treating the purified terephthalic acid(PTA) was proved. It suggests that Ebis would be useful and universal for predicating the technique effectiveness in both DSTS and IWTS.

  8. Mapping Thermal Energy Resource Potentials from Wastewater Treatment Plants

    OpenAIRE

    Georg Neugebauer; Florian Kretschmer; René Kollmann; Michael Narodoslawsky; Thomas Ertl; Gernot Stoeglehner

    2015-01-01

    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 ca...

  9. Remarks on the treatments of non-solvable potentials

    CERN Document Server

    Gonul, B

    2016-01-01

    The recently introduced scheme [20,21] is extended to propose an algebraic non-perturbative approach for the analytical treatment of Schr\\"odinger equations with non-solvable potentials involving an exactly solvable potential form together with an additional piece. As an illustration the procedure is successfully applied to the Cornell potential by means of very simple algebraic manipulations. However, instead of providing numerical eigenvalues for the only consideration of the small strength of the related linear potential as in the previous reports, the present model puts forward a clean route to interpret related experimental or precise numerical results involving wide range of the linear potential strengths. We hope this new technique will shed some light on the questions concerning with the limitations of the traditional perturbation techniques.

  10. Survey of analogue spacetimes

    CERN Document Server

    Visser, Matt

    2013-01-01

    Analogue spacetimes, (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole, (mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid --- and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: Analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this introductory chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  11. Efficacy and safety of treatment with human insulin analogues in daily management of insulin naive patients with type 2 diabetes mellitus: results of multicenter 52-week observational study A1chive

    Directory of Open Access Journals (Sweden)

    Marina Vladimirovna Shestakova

    2012-12-01

    Full Text Available Modern insulin analogues allow safe improvement of glycemic control (not accompanied with increase in body mass or rate of severe hypoglycemic events and its efficient maintenance during long period of time. In this paper we present results of multicenter 52-week prospective observational study A1chive (Russian cohort, n=9342, designed to assess safety and efficacy of treatment with human insulin analogues (Levemir®, NovoMix® 30 and NovoRapid® (Novo Nordisk in daily management of insulin naive patients with type 2 diabetes mellitus. Prescription of human insulin analogues resulted in clinically and statistically significant improvement of glycemic control irrespective of initial insulin regimen. Therapy by various regimens (Levemir®, NovoMix® 30 or Levemir® + NovoRapid® under conditions of daily clinical practice leads to marked improvement in glycemic control as measured by HbA1c (-2.9% in 12 month with no evidence for negative influence on tolerability and short-term safety of the treatment. Furthermore, decrease in HbA1c levels was associated with pronounced and stable decrease in fasting and postprandial glucose levels (-5.0 mmol/L and -5.7 mmol/L, respectively. By the end of the follow-up all regimen groups reported improvement of QoL by treatment satisfaction criterion.

  12. Potential applications of synchrotron radiation to the treatment of cancer

    International Nuclear Information System (INIS)

    Although conventional radiotherapy remains to be one of the most useful treatments for cancer, it is not the best strategy to maximize the effects on the tumors and minimize the damage to the surrounding tissues due to its physical and biological characteristics. Synchrotron radiation (SR) with uniquely physical and biological advantages may represent an innovative approach for cancer treatment. In recent years, SR-based photon activation therapy, stereotactic synchrotron radiation therapy and micro-beam radiation treatment have been developed, and the results of in vitro and in vivo experiments are very promising. It is necessary to understand the physical and radiobiological principle of those novel strategies before the approach is applied to the clinic. In this paper, we summarize the advances of SR in terms of physical, radiobiological advantages and its potential clinical applications. With the successful operation of shanghai synchrotron radiation, good opportunities in China have been provided for investigations on the treatment of cancer with synchrotron radiation. (authors)

  13. Occurrence and profiles of bisphenol analogues in municipal sewage sludge in China

    International Nuclear Information System (INIS)

    Extensive use of bisphenol A and its analogues has caused increasing concern over the potential adverse health impacts of these chemicals. In this study, the presence and profiles of 13 bisphenols (BPs) were investigated in 52 municipal sewage sludge samples collected from 30 cities in China. Tetrabromobisphenol A was the most frequently observed analogue (geometric mean: 20.5 ng/g dw). Bisphenol A (4.69 ng/g dw), bisphenol S (3.02 ng/g dw), and bisphenol F (3.84 ng/g dw) were found with similar frequency. Other BP analogues such as tetrachlorobisphenol A, bisphenol AF, bisphenol E, and dihydroxybiphenyl were identified for the first time in sewage sludge in China. Significant correlations were found among BP concentrations, but no relationships were found with wastewater treatment plant characteristics. Profiles of the relative estradiol equivalents suggested that the estrogenic potential of BP mixtures may be associated with the occurrence and contributions of specific analogues. -- Highlights: • The profiles of various bisphenols were studied initially in sludge in China. • Analogous abundances were found for BPA, BPS and BPF. • Halo-substituted BPs have similar portions with BPA and its ascendant alternatives. • BPAF, TCBPA, BPE and DHBP were identified for the first time in sludge in China. -- We analyzed the profiles of bisphenol analogues in 52 sewage sludge samples with several bisphenols identified for the first time in wastewater treatment plants in China

  14. Aquaponics and its potential aquaculture wastewater treatment and human urine treatment

    OpenAIRE

    Sánchez, Henrique Junior Aiveca

    2014-01-01

    The main objective of this thesis is to study the developing fields of aquaponics and its potential for aquaculture wastewater treatment and human urine treatment. Aquaponics is a food production system which combines fish farming (aquaculture) with soilless crop farming (hydroponics). In this thesis the concept of aquaponics and the underlying processes are explained. Research on aquaculture wastewater and human urine wastewater is reviewed and its potential application with aquaponic sys...

  15. The Potential of Extended Aeration System for Sago Effluent Treatment

    Directory of Open Access Journals (Sweden)

    Wahi A. Rashid

    2010-01-01

    Full Text Available Problem statement: Sago effluent contains large amount of organic material which has a potential to cause water pollution. In order to reduce this problem, an experiment was conducted to remove organic material from sago effluent using lab scale of Extended Aeration (EA system. Approach: The EA system consisted of the combination of physical and biological treatment unit. For Physical Treatment Unit (PTU, the sago effluent was filtered using 710 µm mesh size filter. For Biological Treatment Unit (BTU, the effluent were mixed and aerated with activated sago sludge for 48 h. The treatment efficiency with respect to Biological Oxygen Demand (BOD, Chemical Oxygen Demand (COD and Total Suspended Solid (TSS removal were evaluated and compared with regulatory requirement by Department of Environment, Malaysia. Results: The result showed, the EA system could reduce BOD, COD and TSS up to 84, 87.8 and 73% respectively, however it did not comply with the regulatory requirement. Conclusion: This study suggested the EA system have potential to be apply on sago effluent, however it should be integrated with additional treatment unit to achieve the effluent quality standard.

  16. 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.

  17. 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. PMID:24619620

  18. In vivo pharmacological evaluations of novel olanzapine analogues in rats: a potential new avenue for the treatment of schizophrenia.

    Science.gov (United States)

    Jafari, Somayeh; Huang, Xu-Feng; Andrews, Jessica L; Fernandez-Enright, Francesca

    2013-01-01

    Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4'-methylpiperazin-1'-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4'-methyl-1',4'-diazepan-1'-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally with Olz, OlzEt, OlzHomo (3 or 6 mg/kg/day), or vehicle (n = 8), three times daily at eight-hour intervals for 5 weeks. Furthermore, a phencyclidine (PCP)-treated rat model was used to examine the prevention of PCP-induced hyperlocomotor activity relevant for schizophrenia therapy. Male Sprague Dawley rats were pre-treated with a single dose (3 mg/kg/day) of Olz, OlzEt, OlzHomo, or vehicle (n = 12), for 2 weeks. Locomotor activity was recorded following a subcutaneous injection with either saline or PCP (10 mg/kg). Olz was found to induce weight gain, hyperphagia, visceral fat accumulation, and metabolic changes associated with reduced histamatergic H1 receptor density in the hypothalamus of treated rats. In contrast, OlzEt and OlzHomo presented promising antipsychotic effects, which did not induce weight gain or fat deposition in the treated animals. Behavioural analysis showed OlzEt to attenuate PCP-induced hyperactivity to a level similar to that of Olz; however, OlzHomo showed a lower propensity to inhibit these stereotyped behaviours. Our data suggest that the therapeutic effectiveness of OlzHomo may be delivered at a higher dose than that of Olz and OlzEt. Overall, OlzEt and OlzHomo may offer a better pharmacological profile than Olz for treating patients with schizophrenia. Clinical trials are needed to test this hypothesis.

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

    Science.gov (United States)

    Klinger, Neil V.

    2016-01-01

    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.

  20. Raxibacumab: potential role in the treatment of inhalational anthrax

    OpenAIRE

    Kummerfeldt, Carlos

    2014-01-01

    Carlos E KummerfeldtDivision of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USAAbstract: Anthrax is a highly contagious and potentially fatal human disease caused by Bacillus anthracis, an aerobic, Gram-positive, spore-forming rod-shaped bacterium with worldwide distribution as a zoonotic infection in herbivore animals. Bioterrorist attacks with inhalational anthrax have prompted the development of more effective treatments. Anti...

  1. 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.

  2. Natural analogues and radionuclide transport model validation

    International Nuclear Information System (INIS)

    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)

  3. Synthesis of Tonghaosu Analogues

    Institute of Scientific and Technical Information of China (English)

    SUN Hai; LIN Yingjie; WU Yulin; WU Yikang

    2009-01-01

    Several new analogues of natural antifeedant tonghaosu were synthesized via m-CPBA (m-chloroperoxybenzoic acid) oxidation of corresponding 3-(a-furyl)propanols, Luche reduction of the resulting enone, epoxidation, acid-mediated spiroketalization, and radical mediated dehydration.

  4. An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation.

    Science.gov (United States)

    Shang, Luqing; Wang, Yaxin; Qing, Jie; Shu, Bo; Cao, Lin; Lou, Zhiyong; Gong, Peng; Sun, Yuna; Yin, Zheng

    2014-12-01

    Enterovirus 71 (EV71), one of the major causative agents of Hand-Foot-Mouth Disease (HFMD), causes severe pandemics and hundreds of deaths in the Asia-Pacific region annually and is an enormous public health threat. However, effective therapeutic antiviral drugs against EV71 are rare. Nucleoside analogues have been successfully used in the clinic for the treatment of various viral infections. We evaluated a total of 27 nucleoside analogues and discovered that an adenosine nucleoside analogue NITD008, which has been reported to be an antiviral reagent that specifically inhibits flaviviruses, effectively suppressed the propagation of different strains of EV71 in RD, 293T and Vero cells with a relatively high selectivity index. Triphosphorylated NITD008 (ppp-NITD008) functions as a chain terminator to directly inhibit the RNA-dependent RNA polymerase activity of EV71, and it does not affect the EV71 VPg uridylylation process. A significant synergistic anti-EV71 effect of NITD008 with rupintrivir (AG7088) (a protease inhibitor) was documented, supporting the potential combination therapy of NITD008 with other inhibitors for the treatment of EV71 infections.

  5. Synthesis of piperlongumine analogues and discovery of nuclear factor erythroid 2-related factor 2 (Nrf2) activators as potential neuroprotective agents.

    Science.gov (United States)

    Peng, Shoujiao; Zhang, Baoxin; Meng, Xianke; Yao, Juan; Fang, Jianguo

    2015-07-01

    The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells. PMID:26079183

  6. The Potential of Curcumin in Treatment of Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Raghavendra Sanivarapu

    2016-01-01

    Full Text Available Current treatment for spinal cord injury (SCI is supportive at best; despite great efforts, the lack of better treatment solutions looms large on neurological science and medicine. Curcumin, the active ingredient in turmeric, a spice known for its medicinal and anti-inflammatory properties, has been validated to harbor immense effects for a multitude of inflammatory-based diseases. However, to date there has not been a review on curcumin’s effects on SCI. Herein, we systematically review all known data on this topic and juxtapose results of curcumin with standard therapies such as corticosteroids. Because all studies that compare the two show superior results for curcumin over corticosteroids, it could be true that curcumin better acts at the inflammatory source of SCI-mediated neurological injury, although this question remains unanswered in patients. Because curcumin has shown improvements from current standards of care in other diseases with few true treatment options (e.g., osteoarthritis, there is immense potential for this compound in treating SCI. We critically and systematically summarize available data, discuss clinical implications, and propose further testing of this well-tolerated compound in both the preclinical and the clinical realms. Analyzing preclinical data from a clinical perspective, we hope to create awareness of the incredible potential that curcumin shows for SCI in a patient population that direly needs improvements on current therapy.

  7. The Potential of Curcumin in Treatment of Spinal Cord Injury.

    Science.gov (United States)

    Sanivarapu, Raghavendra; Vallabhaneni, Vijayalakshmi; Verma, Vivek

    2016-01-01

    Current treatment for spinal cord injury (SCI) is supportive at best; despite great efforts, the lack of better treatment solutions looms large on neurological science and medicine. Curcumin, the active ingredient in turmeric, a spice known for its medicinal and anti-inflammatory properties, has been validated to harbor immense effects for a multitude of inflammatory-based diseases. However, to date there has not been a review on curcumin's effects on SCI. Herein, we systematically review all known data on this topic and juxtapose results of curcumin with standard therapies such as corticosteroids. Because all studies that compare the two show superior results for curcumin over corticosteroids, it could be true that curcumin better acts at the inflammatory source of SCI-mediated neurological injury, although this question remains unanswered in patients. Because curcumin has shown improvements from current standards of care in other diseases with few true treatment options (e.g., osteoarthritis), there is immense potential for this compound in treating SCI. We critically and systematically summarize available data, discuss clinical implications, and propose further testing of this well-tolerated compound in both the preclinical and the clinical realms. Analyzing preclinical data from a clinical perspective, we hope to create awareness of the incredible potential that curcumin shows for SCI in a patient population that direly needs improvements on current therapy. PMID:27298735

  8. TRPM8: a potential target for cancer treatment.

    Science.gov (United States)

    Liu, Zhaoguo; Wu, Hongyan; Wei, Zhonghong; Wang, Xu; Shen, Peiliang; Wang, Siliang; Wang, Aiyun; Chen, Wenxing; Lu, Yin

    2016-09-01

    Transient receptor potential (TRP) cation channel superfamily plays critical roles in variety of processes, including temperature perception, pain transduction, vasorelaxation, male fertility, and tumorigenesis. One of seven families within the TRP superfamily of ion channels, the melastatin, or TRPM family comprises a group of eight structurally and functionally diverse channels. Of all the members of TRPM subfamily, TRPM8 is the most notable one. A lot of literatures have demonstrated that transient receptor potential melastatin 8 (TRPM8) could perform a myriad of functions in vertebrates and invertebrates alike. In addition to its well-known function in cold sensation, TRPM8 has an emerging role in a variety of biological systems, including thermoregulation, cancer, bladder function, and asthma. Recent studies have shown that TRPM8 is necessary to the initiation and progression of tumors, and the aberrant expression of TRPM8 was found in varieties of tumors, such as prostate tumor, melanoma, breast adenocarcinoma, bladder cancer, and colorectal cancer, making it a novel molecular target potentially useful in the diagnosis and treatment of cancer. This review outlines our current understanding on the role of TRPM8 in occurrence and development of different kinds of tumor and also includes discussion about the regulation of TRPM8 during carcinogenesis as well as therapeutic potential of targeting TRPM8 in tumor, which may be utilized for a potential pharmacological use as a target for anti-cancer therapy. PMID:26803314

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Polyphenols: Potential Future Arsenals in the Treatment of Diabetes.

    Science.gov (United States)

    Solayman, Md; Ali, Yousuf; Alam, Fahmida; Islam, Md Asiful; Alam, Nadia; Khalil, Md Ibrahim; Gan, Siew Hua

    2016-01-01

    Diabetes mellitus (DM) is one of the most common endocrine metabolic disorders. In addition to exercise and diet, oral anti-diabetic drugs have been used as a part of the management strategy worldwide. Unfortunately, none of the conventional anti-diabetic drugs are without side effects, and these drugs pose an economic burden. Therefore, the investigation of novel anti-diabetic regimens is a major challenge for researchers, in which nature has been the primary resource for the discovery of potential therapeutics. Many plants have been shown to act as anti-diabetic agents, in which the main active constituents are believed to be polyphenols. Natural products containing high polyphenol levels can control carbohydrate metabolism by various mechanisms, such as protecting and restoring beta-cell integrity, enhancing insulin releasing activity, and increasing cellular glucose uptake. Blackberries, red grapes, apricots, eggplant and popular drinks such as coffee, cocoa and green tea are all rich in polyphenols, which may dampen insulin resistance and be natural alternatives in the treatment of diabetes. Therefore, the aim of this review is to report on the available anti-diabetic polyphenols (medicinal plants, fruits and vegetables), their mechanisms in the various pathways of DM and their correlations with DM. Additionally, this review emphasizes the types of polyphenols that could be potential future resources in the treatment of DM via either novel regimens or as supplementary agents.

  14. Polyphenols: Potential Future Arsenals in the Treatment of Diabetes.

    Science.gov (United States)

    Solayman, Md; Ali, Yousuf; Alam, Fahmida; Islam, Md Asiful; Alam, Nadia; Khalil, Md Ibrahim; Gan, Siew Hua

    2016-01-01

    Diabetes mellitus (DM) is one of the most common endocrine metabolic disorders. In addition to exercise and diet, oral anti-diabetic drugs have been used as a part of the management strategy worldwide. Unfortunately, none of the conventional anti-diabetic drugs are without side effects, and these drugs pose an economic burden. Therefore, the investigation of novel anti-diabetic regimens is a major challenge for researchers, in which nature has been the primary resource for the discovery of potential therapeutics. Many plants have been shown to act as anti-diabetic agents, in which the main active constituents are believed to be polyphenols. Natural products containing high polyphenol levels can control carbohydrate metabolism by various mechanisms, such as protecting and restoring beta-cell integrity, enhancing insulin releasing activity, and increasing cellular glucose uptake. Blackberries, red grapes, apricots, eggplant and popular drinks such as coffee, cocoa and green tea are all rich in polyphenols, which may dampen insulin resistance and be natural alternatives in the treatment of diabetes. Therefore, the aim of this review is to report on the available anti-diabetic polyphenols (medicinal plants, fruits and vegetables), their mechanisms in the various pathways of DM and their correlations with DM. Additionally, this review emphasizes the types of polyphenols that could be potential future resources in the treatment of DM via either novel regimens or as supplementary agents. PMID:26601968

  15. 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

  16. The design of potential antidiabetic drugs: experimental investigation of a number of beta-D-glucose analogue inhibitors of glycogen phosphorylase.

    Science.gov (United States)

    Oikonomakos, N G; Kontou, M; Zographos, S E; Tsitoura, H S; Johnson, L N; Watson, K A; Mitchell, E P; Fleet, G W; Son, J C; Bichard, C J

    1994-01-01

    alpha-D-glucose is a weak inhibitor (Ki = 1.7 mM) of glycogen phosphorylase (GP) and acts as physiological regulator of hepatic glycogen metabolism; it binds to GP at the catalytic site and stabilizes the inactive T state of the enzyme promoting the action of protein phosphatase 1 and stimulating glycogen synthase. The three-dimensional structures of T state rabbit muscle GPb and the GPb-alpha-D-glucose complex have been exploited in the design of better regulators of GP that could shift the balance between glycogen synthesis and glycogen degradation in favour of the former. Close examination of the catalytic site with alpha-D-glucose bound shows that there is an empty pocket adjacent to the beta-1-C position. beta-D-glucose is a poorer inhibitor (Ki = 7.4 mM) than alpha-D-glucose, but mutarotation has prevented the binding of beta-D-glucose in T state GP crystals. A series of beta-D-glucose analogues has been designed and tested in kinetic and crystallographic experiments. Several compounds have been discovered that have an increased affinity for GP than the parent compound. PMID:7867660

  17. Comparative study of bisphenol A and its analogue bisphenol S on human hepatic cells: a focus on their potential involvement in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Peyre, Ludovic; Rouimi, Patrick; de Sousa, Georges; Héliès-Toussaint, Cécile; Carré, Benjamin; Barcellini, Sylvie; Chagnon, Marie-Christine; Rahmani, Roger

    2014-08-01

    For several decades, people have been in contact with bisphenol A (BPA) primarily through their diet. Nowadays it is gradually replaced by an analogue, bisphenol S (BPS). In this study, we compared the effects of these two bisphenols in parallel with the positive control diethylstilbestrol (DES) on different hepatocyte cell lines. Using a cellular impedance system we have shown that BPS is less cytotoxic than BPA in acute and chronic conditions. We have also demonstrated that, contrary to BPA, BPS is not able to induce an increase in intracellular lipid and does not activate the PXR receptor which is known to be involved in part, in this process. In parallel, it failed to modulate the expression of CYP3A4 and CYP2B6, the drug transporter ABCB1 and other lipid metabolism genes (FASN, PLIN). However, it appears to have a weak effect on GSTA4 protein expression and on the Erk1/2 pathway. In conclusion, in contrast to BPA, BPS does not appear to induce the metabolic syndrome that may lead to non-alcoholic fatty liver disease (NAFLD), in vitro. Although we have to pay special attention to BPS, its use could be less dangerous concerning this toxicological endpoint for human health.

  18. Methane potential and anaerobic treatment feasibility of Sargassum muticum.

    Science.gov (United States)

    Soto, M; Vázquez, M A; de Vega, A; Vilariño, J M; Fernández, G; de Vicente, M E S

    2015-01-01

    The aim of this research was to study the feasibility of anaerobic digestion of the alga Sargassum muticum with special attention to its biodegradability, potential toxicity caused by its salt content, alga components and intermediate process compounds, and potential limitations to continuous treatment. Specific methane potential (SMP) for three samples of S. muticum collected from the Galician coast (Northwest Spain) at different seasons ranged from 166 to 208 mLCH4/gVS while accumulation of toxic compounds was not observed at alga concentrations of up to 100 gTS/L, except for one of the samples in which inhibition started at 80-100 gTS/L. Continuous digestion is feasible at alga concentration up to 100 gTS/L with methane production rates ranging from 0.14 to 0.26 LCH4/Ld at organic loading rates of 3.2 gTS/Ld, but SMP dropped to 113-159 mLCH4/gVS. PMID:25864031

  19. Bioremediation Potential of Bacterial Isolates for Municipal Wastewater Treatment

    Directory of Open Access Journals (Sweden)

    Nilesh A. Sonune

    2015-08-01

    Full Text Available The potential of bacteria for the treatment of municipal wastewater was investigated in present study. Total eight bacterial isolates were used for this study that showed growth on wastewater agar medium. These isolates were identified on the basis of morphological and biochemical test and identified as Bacillus licheniformis NW16, Pseudomonas aeruginosa NS19, Pseudomonas sp. NS20, Planococcus salinarum NS23, Stenotrophomonas maltophilia NS21, Paenibacillus sp. NW9, Paenibacillus borealis NS3 and Aeromonas hydrophilia NS17. The B. licheniformis NW16 showed highest potential to reduce all parameter under study than other isolates except Ammonical nitrogen. B. licheniformis NW16 and Aeromonas hydrophilia NS17 showed maximum reduction (42.86% in BOD each. B. licheniformis NW16 and Paenibacillus sp. NW9 showed 82.76% and 81.61% reduction in COD respectively. B. licheniformis NW16, P. salinarum NS23 and Aeromonas hydrophilia NS17 showed reduction in nitrate ranging from 17.36%-63.64%. All the isolates have potential to reduced phosphate from 17.55% -72.3%. B. licheniformis NW16, Ps. aeruginosa NS19, Pseudomonas sp. NS20, Paenibacillus sp. NW9 and Aeromonas hydrophilia NS17 showed reduction in TSS ranging from 42.69%-79.94%. B. licheniformis NW16, Ps. aeruginosa NS19, Pseudomonas sp. NS20, S. maltophilia NS21 and Paenibacillus sp. NW9 showed reduction in TDS ranging from 14%-81.4%.

  20. Neuroprotective actions of a histidine analogue in models of ischemic stroke.

    Science.gov (United States)

    Tang, Sung-Chun; Arumugam, Thiruma V; Cutler, Roy G; Jo, Dong-Gyu; Magnus, Tim; Chan, Sic L; Mughal, Mohamed R; Telljohann, Richard S; Nassar, Matthew; Ouyang, Xin; Calderan, Andrea; Ruzza, Paolo; Guiotto, Andrea; Mattson, Mark P

    2007-05-01

    Histidine is a naturally occurring amino acid with antioxidant properties, which is present in low amounts in tissues throughout the body. We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE). We now report that the histidine analogue histidyl hydrazide is effective in reducing brain damage and improving functional outcome in a mouse model of focal ischemic stroke when administered intravenously at a dose of 20 mg/kg, either 30 min before or 60 min and 3 h after the onset of middle cerebral artery occlusion. The histidine analogue also protected cultured rat primary neurons against death induced by HNE, chemical hypoxia, glucose deprivation, and combined oxygen and glucose deprivation. The histidine analogue prevented neuronal apoptosis as indicated by decreased production of cleaved caspase-3 protein. These findings suggest a therapeutic potential for HNE-scavenging histidine analogues in the treatment of stroke and related neurodegenerative conditions. PMID:17254011

  1. A critical appraisal of the role of insulin analogues in the management of diabetes mellitus.

    Science.gov (United States)

    Oiknine, Ralph; Bernbaum, Marla; Mooradian, Arshag D

    2005-01-01

    Insulin is one of the oldest and best studied treatments for diabetes mellitus. Despite many improvements in the management of diabetes, the nonphysiological time-action profiles of conventional insulins remain a significant obstacle. However, the advent of recombinant DNA technology made it possible to overcome these limitations in the time-action profiles of conventional insulins. Used as prandial (e.g. insulin lispro or insulin aspart) and basal (e.g. insulin glargine) insulin, the analogues simulate physiological insulin profiles more closely than the older conventional insulins. If rapid-acting insulin analogues are used in the hospital, healthcare providers will need a new mind-set. Any error in coordination between timing of rapid-acting insulin administration and meal ingestion may result in hypoglycaemia. However, guidelines regarding in-hospital use of insulin analogues are few. The safety profile of insulin analogues is still not completely established in long-term clinical studies. Several studies have shown conflicting results with respect to the tumourigenic potential of this new class of agents. The clinical implications of these findings are not clear. Although novel insulin analogues are promising 'designer drugs' in our armamentarium to overcome some of the limitations of conventional insulin therapy, cost may be a limiting factor for some patients. PMID:15669878

  2. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    Science.gov (United States)

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment.

  3. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    Science.gov (United States)

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. PMID:27301366

  4. Potential role of odanacatib in the treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Ng KW

    2012-07-01

    Full Text Available Kong Wah NgDepartment of Endocrinology and Diabetes and St Vincent’s Institute, St Vincent’s Hospital, Fitzroy, Victoria, AustraliaAbstract: Cathepsin K is a key enzyme involved in the degradation of organic bone matrix by osteoclasts. Inhibition of bone resorption observed in human and animal models deficient for cathepsin K has identified this enzyme as a suitable target for intervention by small molecules with the potential to be used as therapeutic agents in the treatment of osteoporosis. Odanacatib (ODN is a nonbasic selective cathepsin K inhibitor with good pharmacokinetic parameters such as minimal in vitro metabolism, long half-life, and oral bioavailability. In preclinical studies, ovariectomized monkeys and rabbits treated with ODN showed substantial inhibition of bone resorption markers along with increases in bone mineral density (BMD. Significant differences were observed in the effects of ODN treatment compared with those of other antiresorptive agents such as bisphosphonates and denosumab. ODN displayed compartment-specific effects on trabecular versus cortical bone formation, with treatment resulting in marked increases in periosteal bone formation and cortical thickness in ovariectomized monkeys whereas trabecular bone formation was reduced. Furthermore, osteoclasts remained viable. Phase I and II studies conducted in postmenopausal women showed ODN to be safe and well tolerated. After 5 years, women who received ODN 50 mg weekly continuously from year 1 (n = 13, showed BMD increases from baseline of 11.9% at the lumbar spine, 9.8% at the femoral neck, 10.9% at the hip trochanter, and 8.5% at the total hip. Additionally, these subjects maintained a low level of the urine bone resorption marker N-terminal telopeptide/creatinine (-67.4% from baseline through 5 years of treatment, while levels of serum bone-specific alkaline phosphatase remained only slightly reduced relative to baseline (-15.3%. In women who were switched from

  5. 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

  6. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    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...

  7. 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 ...

  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. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    International Nuclear Information System (INIS)

    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

  10. CEC natural analogue working group

    International Nuclear Information System (INIS)

    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

  11. CEC Natural Analogue Working Group

    International Nuclear Information System (INIS)

    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

  12. 胰高血糖素样肽1及其类似物治疗阿尔茨海默病作用机制研究进展%Alzheimer’s Disease and Treatment Progress of GLP-1 Analogues

    Institute of Scientific and Technical Information of China (English)

    唐晶; 董齐; 伊然

    2015-01-01

    Alzheimer’s disease (AD) was found many pathological features and cognitive decline that may be associated with insulin resistance in the brain. The study of AD animal models and patients with mild cognitive dysfunction (MCI) of brain tissue showed that insulin resistance and many pathological features may be reduced or reversed after the treatment with glucagon-likepeptide 1 analogue such as liraglutide, exenatide lyxumia. This is a theoretical basis for the potential treatment of GLP-1 analogues on the results of this study for AD. GLP-1 and its analogues’ potential therapeutic role in AD were reviewed.%研究发现阿尔茨海默病(AD)的许多病理特征和认知功能下降可能与脑内胰岛素抵抗有关。对AD动物模型和轻度认知功能障碍患者的脑组织进行研究,结果表明应用胰高血糖素样肽1(GLP-1)类似物如利拉鲁肽、艾塞那肽治疗后,脑内胰岛素抵抗和许多病理特征减少或是逆转。这一研究结果为GLP-1类似物对AD的潜在治疗研究提供理论基础。对GLP-1及其类似物在AD中的潜在治疗作用做一综述。

  13. 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.

  14. ARE THE MELATONIN SUPPLEMENTS POTENTIAL TREATMENT OPTIONS? A SYSTEMATIC REVIEW

    Directory of Open Access Journals (Sweden)

    Subhranil Saha*, Munmun Koley and Sandip Patra

    2013-10-01

    Full Text Available Introduction: Melatonin is a neuro-hormone secreted from the pineal gland and involved in various regulatory activities in body. Ever-increasing use of melatonin supplements and enlarging research evidences make the authors undertook the review to arrive at a qualitative conclusion whether melatonin supplements can act as potential treatment options or not.Methodology: A comprehensive search was undertaken in different electronic databases using various search terms. A total of 225 studies were identified including clinical research studies and basic experiments. Data were extracted individually from the studies and compiled in the end.Results: Melatonin has been used successfully in chronic insomnia and as an anti-oxidant in cancer and other age-related neuro-degenerative disorders, especially Alzheimer’s disease and Autistic disorders. Its evidences of use in other conditions remained insufficient and inconclusive.Conclusion: Melatonin therapy may be considered as efficacious and safe in insomnia and as an anti-oxidant; however, other roles needs to be evaluated in further studies.

  15. Microwave treatment and struvite recovery potential of dairy manure.

    Science.gov (United States)

    Qureshi, Asif; Lo, Kwang Victor; Liao, Ping Huang

    2008-05-01

    Microwave digestion of liquid dairy manure was tested for the release of nutrients, such as orthophosphates, ammonia-nitrogen, magnesium, calcium and potassium, both with and without the aid of an oxidizing agent (hydrogen peroxide). The orthophosphate to total phosphorus ratio of the manure increased from 21% to greater than 80% with 5 minutes of microwave treatment. More than 36% of total chemical oxygen demand (t-COD) of the manure was reduced when microwave digestion was assisted with peroxide addition. In addition, the volatile fatty acids (VFAs) distribution shifted to simpler chain acids (acetic acid in particular) with an increase in operating temperature. In the second part of the study, digested manure with increased soluble phosphate was tested for the recovery of struvite (magnesium ammonium phosphate) at different pH. It was found that up to 90% of orthophosphate can be removed from the solution. Overall, it was concluded that the oxidizing agent-assisted microwave digestion process can be used upstream of anaerobic digestion, following which the anaerobically digested manure can be used for struvite recovery. Thus, this microwave digestion process presents the potential for enhanced efficiencies in both manure digestion and struvite recovery. PMID:18437623

  16. 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.

  17. Gastric inhibitory polypeptide analogues

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2002-01-01

    of GIP and GLP-1 receptors, the incretin effect is essential for normal glucose tolerance. In patients with type 2 diabetes mellitus it turns out that the incretin effect is severely impaired or abolished. The explanation seems to be that both the secretion of GLP-1 and the effect of GIP are impaired...... (whereas both the secretion of GIP and the effect of GLP-1 are near normal). The impaired GLP-1 secretion is probably a consequence of diabetic metabolic disturbances. The known genetic variations in the GIP receptor sequence are not associated with type 2 diabetes mellitus, but a defective insulinotropic...... and its analogues are attractive as therapeutic agents for type 2 diabetes mellitus, analogues of GIP are unlikely to be effective. On the other hand, GIP seems to play an important role in lipid metabolism, promoting the disposal of ingested lipids, and mice with a targeted deletion of the GIP receptor...

  18. Natural analogue working group

    International Nuclear Information System (INIS)

    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

  19. The Palmottu analogue project

    International Nuclear Information System (INIS)

    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.)

  20. 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.

  1. Ruxolitinib for the treatment of myelofibrosis: its clinical potential

    Directory of Open Access Journals (Sweden)

    Ostojic A

    2012-03-01

    Full Text Available Alen Ostojic1, Radovan Vrhovac1, Srdan Verstovsek21Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb, Zagreb, Croatia; 2Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, USAAbstract: Ruxolitinib is an orally bioavailable, selective Janus kinase (JAK 1 and 2 inhibitor approved for the treatment of myelofibrosis (MF, a bone marrow disease in which the JAK pathway is dysregulated, leading to impaired hematopoiesis and immune function. By inhibiting JAK1 and JAK2, ruxolitinib modulates cytokine-stimulated intracellular signaling. In a phase II clinical trial in patients with MF, ruxolitinib recipients exhibited durable reductions in spleen size, reductions in circulating pro-inflammatory cytokines, improvements in physical activity, weight gain, and alleviation of symptoms (including constitutional symptoms in patients with and without JAK2 mutation. These findings were confirmed by two phase III clinical MF studies, in which a greater proportion of ruxolitinib recipients achieved a spleen volume reduction of ≥35% from baseline at week 24, compared with placebo in one study (41.9% versus 0.7%; P < 0.0001 and with best available therapy in the other (31.9% versus 0%; P < 0.0001. Alleviation of MF symptoms and improvements in quality of life were also significantly greater in ruxolitinib recipients. Overall survival of patients treated with ruxolitinib was significantly longer than of those receiving the placebo. Owing to risks of potentially serious adverse effects, eg, myelosuppression, ruxolitinib should be used under close physician supervision. Longer follow-up of the phase III MF studies is needed to reach firm conclusions regarding ruxolitinib’s capacity to modify the natural disease course.Keywords: myelofibrosis, JAK2 inhibitor, ruxolitinib

  2. Effects of 1-MCP and Its Structural Analogues Treatment on Post-harvest Storage of Tomato%1-MCP及其结构相似物处理对番茄采后贮藏效果的影响

    Institute of Scientific and Technical Information of China (English)

    付琳; 程顺昌; 魏宝东; 冷俊颖; 冯叙桥

    2012-01-01

    Effect of Treatments with 1-MCP and its Structural Analogues on Post-harvest Storage of Tomato was investigated.The effect of three cyclopropene compounds were used as ethylene action inhibitors on postharvest storage and senescence of tomato fruits.Green mature tomato fruits were treated with 1-MCP(1-methylcyclopropene),or its structural analogue 1-PentCP(1-pentylcyclopropene) or 1-OCP(1-octylcyclopropene) and stored at ambient temperature.Physiological and biochemical analyses related to fruit ripening and senescence were conducted every three days during fruit storage.The results indicate that treatment with 1-MCP or its structural analogues inhibited the respiration rate and ethylene production rate of tomato fruits,restrained the decline of fruit firmness remarkably,delayed the raise of soluble solid contents.The activity of POD and CAT in after-ripening stage fruits were inhibited effectively as well.Therefore,the ripening and softening of tomato fruits were postponed by treatment with the compounds.However,the effect decreased when the side chain changed from methyl to pentyl and to octyl.%为了研究环丙烯类乙烯抑制剂的作用效果,以绿熟期番茄为试材,用1-甲基环丙烯(1-MCP)、1-戊基环丙烯(1-PentCP)、1-辛基环丙烯(1-OCP)处理后,常温(18℃±2℃)贮藏,每隔3 d测定1次理化指标,研究三者对番茄果实后熟衰老和贮藏效果的影响。结果表明:1-MCP及其结构相似物处理番茄不同程度地降低了呼吸强度和乙烯释放量的峰值,抑制了番茄果实硬度的下降,延缓了可溶性固形物含量的上升,同时也有效抑制了后熟期番茄果实过氧化氢酶(CAT)活性、过氧化物酶(POD)活性,延缓了果实的后熟衰老。3种试验的抑制剂中,1-MCP、1-PentCP和1-OCP处理随支链长度的增加,抑制后熟衰老的效果依次降低。

  3. The development of somatostatin analogues mediated tumor targeting and therapy

    International Nuclear Information System (INIS)

    Radionuclide labelled somatostatin analogues have been widely used in the detection of neuro-endocrine tumors. Till now, most of somatostatin analogues only have high affinity to somatostatin receptor 2 (SSTR2), further clinical applications was limitted. A new generation of somatostatin analogues such as 1, 4, 7, 10-tetraazacyclodocecane-N, N', N'', N''' -tetaraacetic acid-Na 13- octertide (DOTA-NOC) etc, binding to somatostatin receptors not only SSTR2 but other subtypes has been used mainly in preclinical study. In this review, we discussed these new somatostatin analogues, chelating agent, and their new labelled compounds, these new radionuclide labelled somatostatin analogues may hold great promise for the receptor-mediated tumor imaging and treatments. (authors)

  4. Hepatitis B virus mutations potentially conferring adefovir/ tenofovir resistance in treatment-naive patients

    Institute of Scientific and Technical Information of China (English)

    Rebecca Pastor; Fran(c)ois Habersetzer; Samira Fafi-Kremer; Michel Doffo(e)l; Thomas F Baumert; Jean-Pierre Gut; Fran(c)oise Stoll-Keller; Evelyne Schvoerer

    2009-01-01

    Anti-hepatitis B virus (HBV) therapy leads to the emergence of mutant viral strains during the treatment of chronic hepatitis B with nucleos(t)ides analogues. The existence of HBV variants with primary antiviral resistance may be important for treatment choice. We studied two patients with chronic HBV infection by sequencing the HBV polymerase gene. They had adefovir- and tenofovir-related mutations in the viral polymerase, although they had never been treated. These mutations were rtV214A/rtN238T in one patient and rtA194T in the other. Thus, mutations in untreated patients deserve cautious surveillance. These data indicate that mutations that can theoretically confer adefovir or tenofovir resistance may emerge in treatmentnaive patients.

  5. Synthesis of Novel Isoxazole-contained Analogues of Losartan

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of novel isoxazole-contained analogues of Losartan were designed and synthesized with 1,3-DC reaction. The regioselectivity of the reaction was discussed and the compounds are potential antihypertensive.

  6. Fully analogue photonic reservoir computer.

    Science.gov (United States)

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-01-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers.

  7. 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...... adverse events were other prespecified outcomes. RESULTS: Carotid IMT change did not differ between groups (biphasic -0.009 mm (95% CI -0.022 to 0.004), aspart+detemir 0.000 mm (95% CI -0.013 to 0.013), detemir -0.012 mm (95% CI -0.025 to 0.000)). HbA1c was more reduced with biphasic (-1.0% (95% CI -1.2...

  8. College students' acceptance of potential treatments for ADHD.

    Science.gov (United States)

    Carter, Stacy L

    2005-08-01

    The purpose of the current study was to investigate the influence that the professional occupation of a consultant making a treatment recommendation may have on college students' (82 women and 52 men) acceptance of a proposed treatment for a child displaying characteristics of Attention Deficit/Hyperactivity Disorder. Consultants were special education teachers, school psychologists, or physicians. The study also examined college students' ratings of treatment acceptability associated with three frequently implemented interventions of either nonspecific medication, token economy with response cost, or time-out for children with characteristics of Attention Deficit/Hyperactivity Disorder. Analysis indicated college students found a token economy intervention was the least acceptable recommendation by a physician.

  9. Preparation of 186 Re-MIBI Complex for Myocardial Perfusion Imaging as Potential Replacement of Analogues 99mTc-MIBI

    International Nuclear Information System (INIS)

    The aim of the present study is to label 2-methoxy isobutyl-isonitrile (MIBI) compound with pure 186 Re and study the optimum conditions to prepare the 186 Re-MIBI complex as a stable contrast agent for myocardial perfusion imaging. From the obtained data the complexation of MIBI with 186 Re was carried out of using 1 mg MIBI, 1 mg SnCl2, 3 mg gentesic acid and 1 ml 186 Re(37 MBq) at ph 2 in a boiling water bath for 30 min. The biodistribution studies in mice indicate that, the complex was cleared from the body by kidneys to urinary bladder and finally was eliminated from the body by urine. 186 Re-MIBI demonstrated satisfactory heart uptake and retention like 99mTc-MIBI (8.94% dose/organ at 5 minutes), blood clearance was fast, while liver activity decreased by time and negligible activity in the lunges. The obtained data showed that 186 Re-MIBI as a potential replacement of 99mTc-MIBI for myocardial perfusion imaging

  10. The Potential of Curcumin in Treatment of Spinal Cord Injury

    OpenAIRE

    Raghavendra Sanivarapu; Vijayalakshmi Vallabhaneni; Vivek Verma

    2016-01-01

    Current treatment for spinal cord injury (SCI) is supportive at best; despite great efforts, the lack of better treatment solutions looms large on neurological science and medicine. Curcumin, the active ingredient in turmeric, a spice known for its medicinal and anti-inflammatory properties, has been validated to harbor immense effects for a multitude of inflammatory-based diseases. However, to date there has not been a review on curcumin's effects on SCI. Herein, we systematically review all...

  11. Highly Efficient Synthesis of Two Hyaluronan Trisaccharide Analogues for Potential Hyaluronic Acid Synthases Inhibitors%透明质酸三糖模拟物的高效合成

    Institute of Scientific and Technical Information of China (English)

    魏国华; 杜宇国; Khushi L. Matta

    2009-01-01

    The syntheses of two hyaluronan trisaccharide analogues, naphthyl 0-(3-methoxy-B-D-glucopy-ranosyluronic acid)-(1,3)-O-(2-acetamido-2-deoxy-B-D-glucopyranosyl)-(1,4)-0-B-D-glucopyranosyluronic acid and naphthyl O-(3-methoxy-2-acetamido-2-deoxy-B-D-glucopyranosyl)-(1,4)-O-(B-D-glucopyranosylu-ronic acid)-(1,3 )-O-2-acetamido-2-deoxy-B-D-glucopyranoside, were described. Construction of the target molecules was achieved through a combination of BF_3·Et_2O/toluene system and trichloroacetimidate glycosyia-tion methodology. This is the first report on the synthesis of the 3-methoxyl derivatives, which represent the smallest fragments that incorporate all the structural features of polymeric hyaluronan and can be used for potential hyaluronic acid synthases inhibitors.%设计合成了2个透明质酸(HA)模拟物1和2, 通过最小基团MeO的引入修饰, 模拟天然HA片段的特性, 用于透明质酸合成酶(HAS)催化机理与抑制剂的研究.

  12. 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...

  13. 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.

  14. Present municipal water treatment and potential removal methods

    International Nuclear Information System (INIS)

    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

  15. 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.

  16. Sale of fluoroquinolones in northern Tanzania: a potential threat for fluoroquinolone use in tuberculosis treatment.

    NARCIS (Netherlands)

    Boogaard, J. van den; Semvua, H.H.; Boeree, M.J.; Aarnoutse, R.E.; Kibiki, G.S.

    2010-01-01

    OBJECTIVES: 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

  17. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    Directory of Open Access Journals (Sweden)

    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  18. 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…

  19. 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

  20. The treatment of convected vortices in compressible potential flow

    Science.gov (United States)

    Steinhoff, J.; Ramachandran, K.; Suryanarayanan, K.

    1983-01-01

    A method is described for incorporating line vortices into the three dimensional compressible potential flow equation. A modified Biot-Savart law is used to compute a vortical velocity field, which is added to the gradient of the potential to form a total velocity. A rapidly converging approximate factorization (AFZ) scheme is then used to compute a potential such that the modified potential flow equation as well as the appropriate boundary conditions, based on total velocity, are satisfied. As part of a coupled iteration procedure, the positions of the line vortices are computed so that they convect with the total flow. The method is used to compute the field due to a single line vortex convecting past a wing. This represents an approximation of the effect of a canard or other lifting surface ahead of the wing, which sheds a tip vortex. It is seen that the flow field is substantially modified by the passage of the vortex. Unlike Euler equation schemes, which are also used to compute these flows, the solutions exhibit no numerical diffusion: The convected vortices retain their initial upstream width. Euler solutions, on the other hand, involve a vorticity which is numerically convected in an Eulerian frame and, unless extensive adaptive grid refinement is used they result in vortices with spread as they convect. Also, the potential flow method requires approximately two orders of magnitude less computing time and much less computer storage than the Euler methods.

  1. 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...

  2. Applying Acylated Fucose Analogues to Metabolic Glycoengineering

    OpenAIRE

    Julia Rosenlöcher; Verena Böhrsch; Michael Sacharjat; Véronique Blanchard; Christoph Giese; Volker Sandig; Christian P R Hackenberger; Stephan Hinderlich

    2015-01-01

    Manipulations of cell surface glycosylation or glycan decoration of selected proteins hold immense potential for exploring structure-activity relations or increasing glycoprotein quality. Metabolic glycoengineering describes the strategy where exogenously supplied sugar analogues intercept biosynthetic pathways and are incorporated into glycoconjugates. Low membrane permeability, which so far limited the large-scale adaption of this technology, can be addressed by the introduction of acylated...

  3. Immunotherapy as a Potential Treatment for Chordoma: a Review.

    Science.gov (United States)

    Patel, Shalin S; Schwab, Joseph H

    2016-09-01

    Chordoma is a locally aggressive primary malignancy of the axial skeleton. The gold standard for treatment is en bloc resection, with some centers now advocating for the use of radiation to help mitigate the risk of recurrence. Local recurrence is common, and salvaging local failures is quite difficult. Chemotherapy has been ineffective and small molecule targeted therapy has had only marginal benefits in small subsets of patients with rare tumor phenotypes or refractory disease. Recent successes utilizing immunotherapy in a variety of cancers has led to a resurgence of interest in modifying the host immune system to develop new ways to treat tumors. This review will discuss these studies and will highlight the early studies employing immune strategies for the treatment of chordoma.

  4. 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...

  5. Immunotherapy as a Potential Treatment for Chordoma: a Review.

    Science.gov (United States)

    Patel, Shalin S; Schwab, Joseph H

    2016-09-01

    Chordoma is a locally aggressive primary malignancy of the axial skeleton. The gold standard for treatment is en bloc resection, with some centers now advocating for the use of radiation to help mitigate the risk of recurrence. Local recurrence is common, and salvaging local failures is quite difficult. Chemotherapy has been ineffective and small molecule targeted therapy has had only marginal benefits in small subsets of patients with rare tumor phenotypes or refractory disease. Recent successes utilizing immunotherapy in a variety of cancers has led to a resurgence of interest in modifying the host immune system to develop new ways to treat tumors. This review will discuss these studies and will highlight the early studies employing immune strategies for the treatment of chordoma. PMID:27475804

  6. Vorticity in analogue gravity

    CERN Document Server

    Cropp, Bethan; Turcati, Rodrigo

    2015-01-01

    In the analogue gravity framework, the acoustic disturbances in a moving fluid can be described by an equation of motion identical to a relativistic scalar massless field propagating in a curved spacetime. This description is possible only when the fluid under consideration is barotropic, inviscid and irrotational. In this case, the propagation of the perturbations is governed by an acoustic metric which depends algebrically on the local speed of sound, density and the background flow velocity, the latter assumed to be vorticity free. In this work we provide an straightforward extension in order to go beyond the irrotational constraint. Using a charged --- relativistic and non-relativistic --- Bose--Einstein condensate as a physical system, we show that in the low momentum limit and performing the eikonal approximation we can derive a d'Alembertian equation of motion for the charged phonons where the emergent acoustic metric depends on a flow velocity in the presence of vorticity.

  7. Alligator Rivers analogue project

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    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 rates. Membrane filtration represents an alternative way to achieve biomass retention. In membrane bioreactors, complete biomass retention can be achieved, irrespective of cells capacity to form bi...

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

    OpenAIRE

    Wen Xiong; Derk, Chris T.

    2009-01-01

    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. Multipo...

  10. Review of Natural Compounds for Potential Skin Cancer Treatment

    OpenAIRE

    Chinembiri, Tawona N; Du Plessis, Lissinda H.; Minja Gerber; Hamman, Josias H.; Jeanetta du Plessis

    2014-01-01

    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 melano...

  11. Potential applications of plasma science techniques for water treatment systems

    International Nuclear Information System (INIS)

    The historical evolution of water treatment techniques and their impact on man and his environment are presented. Ancient man recognized the relationship between good water and good health. However, it was not until the late 1800's that man's own contribution to the pollution of water via biological and chemical contamination of the water stream was recognized as having adverse affects on water quality. Since that time virtually every nation has adopted laws and regulations to ensure that safe sources of unpolluted water are available to its citizens. In the United States, water quality is governed by the Clean Water Act of 1972 administered at the federal level by the Environmental Protection Agency (EPA). Further, each state has established its equivalent agency which administers its own laws and regulations. Different biological and chemical biohazards present in the water system are discussed. Biological contaminants include various types of viruses, bacteria, fungii, molds, yeasts, algae, amoebas, and parasites. Chemical contaminates include elemental heavy metals and other organic and inorganic compounds which interfere with normal biological functions. Conventional water treatments for both consumption and sewage effluent commonly employ four different principals: mechanical filtration, quiescent gravity settling, biological oxidation, and chemical treatment. Although these techniques have greatly reduced the incidence of water-borne disease recent studies suggest that more effective means of eliminating biohazards are needed. Regulatory requirements for more aggressive treatment and elimination of residual contaminants present a significant opportunity for the application of various forms of electromagnetic radiation techniques. A comparison between conventional techniques and more advanced methods using various forms of electromagnetic radiation is discussed

  12. Potential of Decentralised Wastewater Treatment Systems Applicable to India

    Directory of Open Access Journals (Sweden)

    Jitesh Arora

    2016-08-01

    Full Text Available Appropriate sanitation facilities are still a challenge in many parts of the world, particularly in developing countries. With regard to almost 950 million people defecating in the open, the question arises whether the existing treatment facilities are sufficient to provide for a healthy sanitation in the world. This paper mainly emphasizes on developing countries (particularly, India where cost is generally a very important parameter of judgment for choosing the appropriate system. This makes decentralized treatment systems much more suitable for installation as they are easier to build and operate, both financially and technically. This paper includes basic differences and fundamental explanations about the processes involved in different decentralized treatment systems and their comparison on the basis of installation cost carried out by using a technology ranking method. It is concluded that waste stabilisation ponds would be most cost effective solution from capital investment point of view. However, Multi Criteria Analysis (MCA should be carried out for appropriate technology selection in different scenarios on the basis of different criteria. New developments in sanitation technologies can play an important role in selecting appropriate sanitation technology for a particular scenario.

  13. 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.

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

    International Nuclear Information System (INIS)

    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

  15. 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

  16. Pyridine analogues of curcumin exhibit high activity for inhibiting CWR-22Rv1 human prostate cancer cell growth and androgen receptor activation

    Science.gov (United States)

    ZHOU, DAI-YING; ZHAO, SU-QING; DU, ZHI-YUN; ZHENG, XI; ZHANG, KUN

    2016-01-01

    The concentrations required for curcumin to exert its anticancer activity (IC50, 20 µM) are difficult to achieve in the blood plasma of patients, due to the low bioavailability of the compound. Therefore, much effort has been devoted to the development of curcumin analogues that exhibit stronger anticancer activity and a lower IC50 than curcumin. The present study investigated twelve pyridine analogues of curcumin, labeled as groups AN, BN, EN and FN, to determine their effects in CWR-22Rv1 human prostate cancer cells. The inhibitory effects of these compounds on testosterone (TT)-induced androgen receptor (AR) activity was determined by performing an AR-linked luciferase assay and by TT-induced expression of prostate-specific antigen. The results of the current study suggested that the FN group of analogues had the strongest inhibitory effect of growth on CWR-22Rv1 cultured cells, and were the most potent inhibitor of AR activity compared with curcumin, and the AN, BN and EN analogues. Thus, the results of the present study indicate the inhibition of the AR pathways as a potential mechanism for the anticancer effect of curcumin analogues in human prostate cancer cells. Furthermore, curcumin analogues with pyridine as a distal ring and tetrahydrothiopyran-4-one as a linker may be good candidates for the development of novel drugs for the treatment of prostate cancer, by targeting the AR signaling pathway. PMID:27313760

  17. Potential role of odanacatib in the treatment of osteoporosis

    OpenAIRE

    Ng KW

    2012-01-01

    Kong Wah NgDepartment of Endocrinology and Diabetes and St Vincent’s Institute, St Vincent’s Hospital, Fitzroy, Victoria, AustraliaAbstract: Cathepsin K is a key enzyme involved in the degradation of organic bone matrix by osteoclasts. Inhibition of bone resorption observed in human and animal models deficient for cathepsin K has identified this enzyme as a suitable target for intervention by small molecules with the potential to be used as therapeutic agents in the treatm...

  18. Synthesis and evaluation of novel carbocyclic carbohydrate analogues

    OpenAIRE

    Adamson, Christopher William

    2016-01-01

    Carbohydrate analogues play an indispensible role in the study of glycan processing enzymes. These compounds have attracted attention as probes of enzyme mechanisms, as chemical tools for the elucidation of enzyme function and as potential pharmaceuticals. The development of organocatalytic aldol chemistry has fundamentally altered the way chemists approach the synthesis of carbohydrate analogues. In this thesis I highlight a novel strategy toward the synthesis of carbocyclic carbohydrate ana...

  19. Global Warming Potential Of A Waste Refinery Using Enzymatic Treatment

    DEFF Research Database (Denmark)

    Tonini, Davide; Astrup, Thomas

    2010-01-01

    Decrease of fossil fuel dependence and resource saving has become increasingly important during the last years. In this perspective, higher recycling rates for valuable materials as well as energy recovery from waste streams could play a significant role substituting for virgin material production...... treatment of municipal solid waste (MSW) was presented. The refinery produced a liquid (liquefied organic materials and paper) and a solid fraction (non-degradable materials) from the initial waste. A number of scenarios for the utilization of the two outputs were analyzed. Co-combustion in existing power...

  20. Blue-Print Autophagy: Potential for Cancer Treatment.

    Science.gov (United States)

    Ruocco, Nadia; Costantini, Susan; Costantini, Maria

    2016-07-21

    The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine natural products involved in stimulation and inhibition of autophagy (a type of programmed cell death) linked to pharmacological and pathological conditions. Autophagy represents a complex multistep cellular process, wherein a double membrane vesicle (the autophagosome) captures organelles and proteins and delivers them to the lysosome. This natural and destructive mechanism allows the cells to degrade and recycle its cellular components, such as amino acids, monosaccharides, and lipids. Autophagy is an important mechanism used by cells to clear pathogenic organism and deal with stresses. Therefore, it has also been implicated in several diseases, predominantly in cancer. In fact, pharmacological stimulation or inhibition of autophagy have been proposed as approaches to develop new therapeutic treatments of cancers. In conclusion, this blue-print autophagy (so defined because it is induced and/or inhibited by marine natural products) represents a new strategy for the future of biomedicine and of biotechnology in cancer treatment.

  1. Blue-Print Autophagy: Potential for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Nadia Ruocco

    2016-07-01

    Full Text Available The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine natural products involved in stimulation and inhibition of autophagy (a type of programmed cell death linked to pharmacological and pathological conditions. Autophagy represents a complex multistep cellular process, wherein a double membrane vesicle (the autophagosome captures organelles and proteins and delivers them to the lysosome. This natural and destructive mechanism allows the cells to degrade and recycle its cellular components, such as amino acids, monosaccharides, and lipids. Autophagy is an important mechanism used by cells to clear pathogenic organism and deal with stresses. Therefore, it has also been implicated in several diseases, predominantly in cancer. In fact, pharmacological stimulation or inhibition of autophagy have been proposed as approaches to develop new therapeutic treatments of cancers. In conclusion, this blue-print autophagy (so defined because it is induced and/or inhibited by marine natural products represents a new strategy for the future of biomedicine and of biotechnology in cancer treatment.

  2. IL-35: a potential target for the treatment of atherosclerosis.

    Science.gov (United States)

    Huang, Ying; Lin, Ying-Zhong; Shi, Ying; Ji, Qing-Wei

    2013-10-01

    The imbalance of anti- inflammatory/pro-inflammatory cytokines plays an important role in the process of atherosclerosis. IL-35 is an anti-inflammatory cytokine comprising the p35 subunit of IL-12 and the subunit Epstein-Barr virus (EBV) -induced gene 3(EBI3). Accumulating evidence showed that IL-35 up-regulates the expression of anti-inflammatory cytokines, induces the generation of CD4 + regulatory T cells, inhibits CD4 + effector T cells response and other target cells activity, and reduces the progression of inflammatory and autoimmune diseases. In addition, it has been found that Ebi3 and p35 strongly coexpressed in human advanced lesions. Therefore, we hypothesize that IL-35 may become a novel target for the treatment of atherosclerosis. Further studies are required to investigate the precise effect and the signaling pathway of IL-35 in atherosclerosis process.

  3. Bone Marrow Stem Cell as a Potential Treatment for Diabetes

    Directory of Open Access Journals (Sweden)

    Ming Li

    2013-01-01

    Full Text Available Diabetes mellitus (DM is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs and tissue stem cells (TSCs to generate functional β cells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM.

  4. Potential of rapid heat treatment of titanium alloys and steels

    Energy Technology Data Exchange (ETDEWEB)

    Ivasishin, O.M.; Teliovich, R.V. [Institute of Metal Physics, Kiev (Ukraine)

    1999-05-15

    Rapid heat treatment (RHT) of titanium alloys and steels, which includes rapid heating into the single-phase field, {beta} and {gamma} of titanium alloys and steels, respectively, is reviewed. Heating rate is an important parameter that affects the mechanism and kinetics of phase and/or structural transformation. Refinement of grain structure, formation of micro-chemical inhomogeneity and substructure in the high temperature phase following RHT are addressed. Thermo-kinetic effects during rapid heating of material with an initial metastable (quenched or deformed) microstructure are discussed. The response of titanium alloys and steels to RHT is compared. The improvement in mechanical properties of both material system following RHT is also presented. (orig.) 48 refs.

  5. Synthetic Routes and Biological Evaluation of Largazole and Its Analogues as Potent Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Sheng Jiang

    2011-06-01

    Full Text Available Natural products with interesting biological properties and structural diversity have often served as valuable lead drug candidates for the treatment of various human diseases. Largazole, isolated from the marine cyanobacterium Symploca sp. has exhibited potent inhibitory activity against many cancer cell lines. Besides, it shows remarkable selectivity between transformed and nontransformed cells, which is the main disadvantage of other antitumor natural products such as paclitaxel and actinomycin D. Due to its potential as a potent and selective anticancer drug candidate, a great deal of attention has been focused on largazole and its analogues. It is the aim of this review to highlight synthetic aspects of largazole and its analogues as well as their preliminary structure–activity relationship studies.

  6. Studies of natural analogues and geological systems

    International Nuclear Information System (INIS)

    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

  7. Nutrient Abatement Potential and Abatement Costs of Waste Water Treatment Plants in the Baltic Sea Region

    OpenAIRE

    Hautakangas, Sami; Ollikainen, Markku; Aarnos, Kari; Rantanen, Pirjo

    2013-01-01

    We assess the physical potential to reduce nutrient loads from waste water treatment plants in the Baltic Sea region and determine the costs of abating nutrients based on the estimated potential. We take a sample of waste water treatment plants of different size classes and generalize its properties to the whole population of waste water treatment plants. Based on a detailed investment and operational cost data on actual plants, we develop the total and marginal abatement cost functions for b...

  8. 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.

  9. Neem components as potential agents for cancer prevention and treatment.

    Science.gov (United States)

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2014-08-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  10. Emerging potential treatments: new hope for idiopathic pulmonary fibrosis patients?

    Directory of Open Access Journals (Sweden)

    U. Costabel

    2011-09-01

    Full Text Available Currently, there are no approved pharmacological treatments for the management of patients with idiopathic pulmonary fibrosis (IPF in the USA or Europe. Pirfenidone is an orally bio-available small molecule that exhibits antifibrotic and anti-inflammatory properties in a variety of in vitro and animal models. Pirfenidone has been evaluated in four randomised, double-blind, placebo-controlled clinical trials conducted in Japan, North America and Europe. The totality of the data from these trials indicates that pirfenidone is able to reduce the rate of decline in lung function, measured as change in per cent predicted forced vital capacity (FVC or vital capacity. There was also an effect on secondary end-points of progression free survival, categorical change in per cent predicted FVC, and the 6-min walk test. A recent meta-analysis of the three phase III studies in IPF demonstrated that pirfenidone significantly reduced the risk of disease progression by 30%. The efficacy of pirfenidone is associated with an acceptable tolerability and safety profile.

  11. Neem components as potential agents for cancer prevention and treatment.

    Science.gov (United States)

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2014-08-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment.

  12. Clinical potential of apremilast in the treatment of psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Cauli A

    2014-06-01

    Full Text Available Alberto Cauli, Giovanni Porru, Matteo Piga, Alessandra Vacca, Grazia Dessole, Alessandro MathieuRheumatology Unit, Department of Medical Sciences, Policlinico of University of Cagliari, Monserrato, ItalyAbstract: Psoriatic arthritis (PsA is a frequent chronic inflammatory disease characterized by joint and skin involvement, and by typical extra-articular manifestations. Although the pathogenesis of PsA is still under investigation, the available evidence suggests the importance of the patient's genetic background, microbial or environmental triggers, and an imbalance in the adaptive and acquired immune system, resulting in the production of inflammatory mediators. New therapeutic approaches have been proposed, among them the use of modulators of intracellular signals and gene transcription such as PDE4-inhibiting compounds, which are able to modulate the activity of transcription factors such as CREB and NF-κB and therefore the synthesis of inflammatory mediators, resulting in immunoregulation. This paper summarizes the mechanism of action of apremilast, a PDE4 inhibitor, and the clinical data available on its clinical efficacy and safety profile in the treatment of PsA patients.Keywords: psoriatic arthritis, apremilast, therapy

  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. DYRK1A inhibition as potential treatment for Alzheimer's disease.

    Science.gov (United States)

    Stotani, Silvia; Giordanetto, Fabrizio; Medda, Federico

    2016-04-01

    In total, 47,500,000 people worldwide are affected by dementia and this number is estimated to double by 2030 and triple within 2050 resulting in a huge burden on public health. Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia, accounting for 60-70% of all the cases. The cause of AD is still poorly understood but several brain abnormalities (e.g., loss of neuronal connections and neuronal death) have been identified in affected patients. In addition to the accumulation of β-amyloid plaques in the brain tissue, aberrant phosphorylation of tau proteins has proved to increase neuronal death. DYRK1A phosphorylates tau on 11 different Ser/Thr residues, resulting in the formation of aggregates called 'neurofibrillary tangles' which, together with amyloid plaques, could be responsible for dementia, neuronal degeneration and cell death. Small molecule inhibition of DYRK1A could thus represent an interesting approach toward the treatment of Alzheimer's and other neurodegenerative diseases. Herein we review the current progress in the identification and development of DYRK1A inhibitors. PMID:27073990

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Francesco Landi

    2016-01-01

    Full Text Available 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. 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

    2016-02-01

    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

  18. Is Selenium a Potential Treatment for Cancer Metastasis?

    Directory of Open Access Journals (Sweden)

    Yu-Chi Chen

    2013-04-01

    Full Text Available Selenium (Se is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent.

  19. 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.

  20. Aβ-degrading enzymes: potential for treatment of Alzheimer disease.

    Science.gov (United States)

    Miners, James Scott; Barua, Neil; Kehoe, Patrick Gavin; Gill, Steven; Love, Seth

    2011-11-01

    There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), insulin-degrading enzyme, and endothelin-converting enzyme reduce Aβ levels and protect against cognitive impairment in mouse models of AD. The activity of several Aβ-degrading enzymes rises with age and increases still further in AD, perhaps as a physiological response to minimize the buildup of Aβ. The age- and disease-related changes in expression of more recently recognized Aβ-degrading enzymes (e.g. NEP-2 and cathepsin B) remain to be investigated, and there is strong evidence that reduced NEP activity contributes to the development of cerebral amyloid angiopathy. Regardless of the role of Aβ-degrading enzymes in the development of AD, experimental data indicate that increasing the activity of these enzymes (NEP in particular) has therapeutic potential in AD, although targeting their delivery to the brain remains a major challenge. The most promising current approaches include the peripheral administration of agents that enhance the activity of Aβ-degrading enzymes and the direct intracerebral delivery of NEP by convection-enhanced delivery. In the longer term, genetic approaches to increasing the intracerebral expression of NEP or other Aβ-degrading enzymes may offer advantages.

  1. 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

  2. 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

  3. Multiple sclerosis : MRI diagnosis, potential treatment and future potential for nanoparticle applications

    OpenAIRE

    Wu, Xingchen

    2005-01-01

    Multiple Sclerosis is an inflammatory demyelinating and neurodegenerative disease of the central nervous system. Magnetic resonance imaging is an important tool for diagnosing of Multiple Sclerosis and for, in vivo, monitoring its evolution of pathology. The introduction of interferon (IFN)-beta therapy has altered the natural course of Multiple Sclerosis. We investigated the effect of low-dose low-frequency and high-dose highfrequency IFNbeta- 1a treatment in patients w...

  4. From BPA to its analogues: Is it a safe journey?

    Science.gov (United States)

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? PMID:27262103

  5. Synthesis and biological evaluation of CTP synthetase inhibitors as potential agents for the treatment of African trypanosomiasis.

    Science.gov (United States)

    Tamborini, Lucia; Pinto, Andrea; Smith, Terry K; Major, Louise L; Iannuzzi, Maria C; Cosconati, Sandro; Marinelli, Luciana; Novellino, Ettore; Lo Presti, Leonardo; Wong, Pui E; Barrett, Michael P; De Micheli, Carlo; Conti, Paola

    2012-09-01

    Acivicin analogues with an increased affinity for CTP synthetase (CTPS) were designed as potential new trypanocidal agents. The inhibitory activity against CTPS can be improved by increasing molecular complexity, by inserting groups able to establish additional interactions with the binding pocket of the enzyme. This strategy has been pursued with the synthesis of α-amino-substituted analogues of Acivicin and N1-substituted pyrazoline derivatives. In general, there is direct correlation between the enzymatic activity and the in vitro anti-trypanosomal efficacy of the derivatives studied here. However, this cannot be taken as a general rule, as other important factors may play a role, notably the ability of uptake/diffusion of the molecules into the trypanosomes. PMID:22865834

  6. Synthesis and biological evaluation of CTP synthetase inhibitors as new potential agents for the treatment of African Trypanosomiasis

    Science.gov (United States)

    Tamborini, L.

    2013-01-01

    Acivicin analogues with an increased affinity for CTP synthetase (CTPS) were designed as potential new trypanocidal agents. The inhibitory activity against CTPS can be improved by increasing the molecular complexity, by inserting groups able to establish additional interaction with the binding pocket of the enzyme. This strategy has been pursued with the synthesis of α-amino-substituted analogues of Acivicin and N1-substituted-pyrazoline derivatives. In general, there is a direct correlation between the enzymatic activity and the in vitro anti-trypanosomal efficacy of the derivatives studied here. However, this cannot be taken as a general rule, since other important factors may play a role, notably the ability of uptake / diffusion of the molecules into the trypanosomes. PMID:22865834

  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. Thymidine Analogues for Tracking DNA Synthesis

    Directory of Open Access Journals (Sweden)

    Brenton L. Cavanagh

    2011-09-01

    Full Text Available Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in “tagging DNA synthesis” is the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU. The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using ‘Huisgen’s reaction’ (1,3-dipolar cycloaddition or ‘click chemistry’. This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other “unnatural bases”. These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.

  9. 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...... axis, the half-life of LH was estimated to be 1.3 h and that of testosterone 7.69 h, which corresponds well with literature values. The estimated potency of LH with respect to testosterone secretion was 5.18 IU l-1, with a maximal stimulation of 77.5 times basal testosterone production. The estimated...

  10. Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment.

    Science.gov (United States)

    Brohée, Laura; Demine, Stéphane; Willems, Jérome; Arnould, Thierry; Colige, Alain C; Deroanne, Christophe F

    2015-05-10

    Lipogenesis inhibition was reported to induce apoptosis and repress proliferation of cancer cells while barely affecting normal cells. Lipins exhibit dual function as enzymes catalyzing the dephosphorylation of phosphatidic acid to diacylglycerol and as co-transcriptional regulators. Thus, they are able to regulate lipid homeostasis at several nodal points. Here, we show that lipin-1 is up-regulated in several cancer cell lines and overexpressed in 50 % of high grade prostate cancers. The proliferation of prostate and breast cancer cells, but not of non-tumorigenic cells, was repressed upon lipin-1 knock-down. Lipin-1 depletion also decreased cancer cell migration through RhoA activation. Lipin-1 silencing did not significantly affect global lipid synthesis but enhanced the cellular concentration of phosphatidic acid. In parallel, autophagy was induced while AKT and ribosomal protein S6 phosphorylation were repressed. We also observed a compensatory regulation between lipin-1 and lipin-2 and demonstrated that their co-silencing aggravates the phenotype induced by lipin-1 silencing alone. Most interestingly, lipin-1 depletion or lipins inhibition with propranolol sensitized cancer cells to rapamycin. These data indicate that lipin-1 controls main cellular processes involved in cancer progression and that its targeting, alone or in combination with other treatments, could open new avenues in anticancer therapy.

  11. Long-acting insulin analogues (insulin glargine or determir) and continuous subcutaneous insulin infusion in the treatment of type 1 diabetes mellitus in the paediatric population.

    Science.gov (United States)

    Barrio Castellanos, Raquel

    2005-12-01

    Despite many improvements in the treatment of type 1 diabetes mellitus (DM1), the non-physiological time-action profiles of conventional insulins remain a significant obstacle. In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular and NPH insulin. The rapid insulin analogs used as prandial and the long-acting insulin analogs used as basal simulate physiological insulin profiles more closely than the older conventional insulins. The efficacy of insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in DM1 has been established in pediatric patients. Insulin pumps have improved since they were first introduced. CSII therapy may provide an effective alternative for selected pediatric patients with DM1. In most studies at pediatric age, CSII therapy resulted in a improvement in HbA1c, a decreased rate of hypoglycemia without an abnormal increase in BMI, and without adversely affecting psychosocial outcomes in children and adolescents with DM1. PMID:16398447

  12. Central effects of angiotensin II, its fragment and analogues.

    Science.gov (United States)

    Georgiev, V P; Klousha, V E; Petkov, V D; Markovska, V L; Svirskis, S V; Mountsinietse, R K; Anouans, Z E

    1984-01-01

    The effects of the octapeptide angiotensin II (AT II), its fragment Ile8 AT3-8 and the analogues Sar1 Ala8 AT II, Ala8 AT II and Ile8 AT II were studied with respect to: the level of biogenic amines (DA, 5-HT and their metabolites HVA and 5-HIAA) in the forebrain; the behaviour of the animals--haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction (UJR), convulsive threshold. Good correlation was found between the biochemical and behavioural effects. The fragment of AT II where phenylalanine is substituted at the C-terminal by Ile reduces the haloperidol-increased content of HVA, potentiates apomorphine stereotypy and reduces catalepsy, whereas the AT II analogues (where the C-terminal phenylalanine is substituted by Ala, and the N-terminal--by Sar) potentiate the effect of haloperidol increasing the HVA content, reduce apomorphine stereotypy and potentiate catalepsy; saralasine independently applied induces brief catalepsy; AT II, its fragment and analogues inhibit UJR, in combination with amphetamine and PTZ this effect becomes deeper; the duration of hexobarbital sleep is increased. The peptides investigated increase the convulsive threshold. The results show that the hexapeptide fragment has preserved the effects of AT II, whereas in the analogues (with changed C- and N-terminals) they are changed. The results obtained may be explained with the modulating influence of AT II-receptors on the DA-ergic receptors in the brain structures with which AT II and its fragment and analogues enter in contact.

  13. 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.

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

    International Nuclear Information System (INIS)

    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

  15. Assessment of potential greenhouse gas mitigation of available household solid waste treatment technologies

    OpenAIRE

    Hoang Minh Giang; guyen Duc Luong; Luong Thi Mai Huong

    2013-01-01

    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 compost...

  16. 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...

  17. Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity

    DEFF Research Database (Denmark)

    Laursen, Jane B.; De Visser, Peter C.; Nielsen, Henrik K.;

    2002-01-01

    in parallel with a series of differently substituted benzoic acid derivatives. Treatment with TFA-CH2Cl2 (5:995) released the expected saphenamycin analogues into solution. These new analogues were purified, characterized and screened for antimicrobial activity against Bacillus subtilis and Proteus mirabilis...

  18. 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

  19. The Potential of Osteopathic Manipulative Treatment in Antimicrobial Stewardship: A Narrative Review.

    Science.gov (United States)

    Noll, Donald R

    2016-09-01

    The contemporary management of infectious diseases is built around antimicrobial therapy. However, the development of antimicrobial resistance threatens to create a post-antibiotic era. Antimicrobial stewardship attempts to reduce the development of antimicrobial resistance by improving their appropriate use. Osteopathic manipulative treatment as an adjunctive treatment has the potential for enhancing antimicrobial stewardship by enhancing the human immune system, shortening the duration of antimicrobial therapy, reducing complications, and improving treatment outcomes. The present article reviews the evidence published in the literature since this unique treatment approach was first developed more than 100 years ago. The evidence suggests that adjunctive osteopathic manipulative treatment has great potential for enhancing antimicrobial stewardship and should be further investigated.

  20. 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...

  1. 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

  2. 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.

  3. Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

    Science.gov (United States)

    López-Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T; Beutler, John A; Echavarren, Antonio M

    2016-05-01

    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).

  4. Effects of thermal pre-treatments on solid slaughterhouse waste methane potential

    OpenAIRE

    Rodríguez-Abalde, Ángela; Fernández García, Belén; Silvestre, Gracia; Flotats Ripoll, Xavier

    2011-01-01

    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 ºC for 60 min) and sterilization (133 ºC and 3 bars for 20 min), are included in the current European regulations for the dispo...

  5. Latrepirdine, a potential novel treatment for Alzheimer’s disease and Huntington’s chorea

    OpenAIRE

    Sabbagh, Marwan N.; Shill, Holly A.

    2010-01-01

    Latrepirdine (Dimebon) is a novel compound currently under development by Medivation Inc and Pfizer Inc for the treatment of Alzheimer’s disease and Huntington’s chorea. Originally developed and marketed as an antihistamine in Russia, it has potential for the treatment of neurodegenerative diseases. Early research suggested that the mechanism of action is centered on AChE inhibition and NMDA antagonism. Newer research casts some doubt regarding these early findings and other mechanisms of act...

  6. [Prevention and Information for Patients Undergoing Periodontal Treatment: Potentials for Improvement from the Patients' Perspective].

    Science.gov (United States)

    Klingenberg, A; Walther, W; Dörfer, C E; Szecsenyi, J

    2016-05-01

    2 334 patients from 29 dental practices took part in a written survey on their experiences with dental treatment in general as well as treatment of periodontal disease (response rate 80.8%). 72.6% of all participating patients fully agreed that they could recommend their dentist to their friends. 63.6% of patients undergoing treatment of periodontitis (N=328) rated this treatment as "excellent". However, for important aspects (prevention, patient information, treatment) potentials for improvement became obvious. 43.7% of patients treated for periodontitis were not completely satisfied with information on how this disease develops; 40.7% saw potentials for better information on preventive care (dental-hygiene, nutrition). An even higher percentage of patients actually not treated for periodontitis was interested in more information on prevention (51.4%). The results of the survey show that dentists should offer information and exercise on how to prevent periodontal desease more actively. There is a lack of research on the present state of affairs and potentials for improvement concerning treatment and prevention of periodontitis including the patients' perspective. PMID:26086539

  7. Analogue Kerr-like geometries in a MHD inflow

    CERN Document Server

    Noda, Sousuke; Takahashi, Masaaki

    2016-01-01

    We present a model of the analogue black hole in magnetohydrodynamic (MHD) flow. For a two dimensional axisymmetric stationary trans-magnetosonic inflow with a sink, using the dispersion relation of the MHD waves, we introduce the effective geometries for magnetoacoustic waves propagating in the MHD flow. Investigating the properties of the effective potentials for magnetoacoustic rays, we find that the effective geometries can be classified into five types which include analogue spacetimes of the Kerr black hole, ultra spinning stars with ergoregions and spinning stars without ergoregions. We address the effects of the magnetic pressure and the magnetic tension on each magnetoacoustic geometries.

  8. Perspectives on purine analogues.

    Science.gov (United States)

    Cheson, B D

    1996-12-01

    The purine analogs, fludarabine, 2-chlorodeoxy-adenosine, and 2'-deoxycoformycin, have revolutionized our approach to the treatment of a variety of indolent lymphoid malignancies. Because of their impressive single agent activity, they should be considered as an initial therapeutic option, not only for hairy cell leukemia, but also for chronic lymphocytic leukemia, indolent non-Hodgkin's lymphomas, and Waldenström's macroglobulenemia. Combinations of purine analogs with alkylatng agents, topisomerase II inhibitors, and other new compounds are in development, and their role as radiation sensitizers is being explored in clinical trials. Substantial activity has also been noted in several of the rheumatologic and immunologic disorders, and in multiple sclerosis. Continued progress requires innovative strategies which can modulate the biology and immunology of these diseases toward the goal of curing these patients. PMID:9137964

  9. Anti-inflammatory and Immune Regulatory Properties of 5-Androsten-3{beta}, 17{beta}-Diol (HE2100), and Synthetic Analogue HE3204: Implications for Treatment of Autoimmune Diseases.

    NARCIS (Netherlands)

    Auci, D.; Nicoletti, F.; Mangano, K.; Pieters, R.; Nierkens, S.; Morgan, L.; Offner, H.; Frincke, J.; Reading, C.

    2005-01-01

    5-Androsten-3beta, 17beta-diol (HE2100), and a synthetic analogue HE3204 are regarded as immune-regulating hormones, because both induce changes in the reporter antigen-popliteal lymph node assay (RA-PLNA). Mice were injected in the footpad with either HE2100 or HE3204 (0.01-3 mg), and a nonsensitiz

  10. 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.

  11. Conception, synthesis, and biological evaluation of original discodermolide analogues.

    Science.gov (United States)

    de Lemos, Elsa; Agouridas, Evangelos; Sorin, Geoffroy; Guerreiro, Antonio; Commerçon, Alain; Pancrazi, Ange; Betzer, Jean-François; Lannou, Marie-Isabelle; Ardisson, Janick

    2011-08-29

    Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive "U" shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)-diene moiety, of the methyl group at the C14-position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.

  12. Synthesis and cytotoxic activity of novel curcumin analogues

    Institute of Scientific and Technical Information of China (English)

    Qin Zhang; Yao Fu; Hao Wei Wang; Tao Gong; Yong Qin; Zhi Rong Zhang

    2008-01-01

    Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues (1A-1C, 1E) with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.

  13. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    Science.gov (United States)

    Tadpetch, Kwanruthai; Kaewmee, Benyapa; Chantakaew, Kittisak; Kantee, Kawalee; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines.

  14. 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.

  15. Novel analogue of colchicine induces selective pro-death autophagy and necrosis in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Kristen Larocque

    Full Text Available Colchicine, a natural product of Colchicum autumnae currently used for gout treatment, is a tubulin targeting compound which inhibits microtubule formation by targeting fast dividing cells. This tubulin-targeting property has lead researchers to investigate the potential of colchicine and analogs as possible cancer therapies. One major study conducted on an analogue of allocolchicine, ZD 6126, was halted in phase 2 clinical trials due to severe cardio-toxicity associated with treatment. This study involves the development and testing of novel allocolchicine analogues that hold non-toxic anti-cancer properties. Currently we have synthesized and evaluated the anti-cancer activities of two analogues; N-acetyl-O-methylcolchinol (NSC 51046 or NCME, which is structurally similar to ZD 6126, and (S-3,8,9,10-tetramethoxyallocolchicine (Green 1, which is a novel derivative of allocolchicine that is isomeric in the A ring. NSC 51046 was found to be non-selective as it induced apoptosis in both BxPC-3 and PANC-1 pancreatic cancer cells and in normal human fibroblasts. Interestingly, we found that Green 1 was able to modestly induce pro-death autophagy in these pancreatic cancer cells and E6-1 leukemia cells but not in normal human fibroblasts. Unlike colchicine and NSC 51046, Green 1 does not appear to affect tubulin polymerization indicating that it has a different molecular target. Green 1 also caused increased reactive oxygen species (ROS production in mitochondria isolated from pancreatic cancer cells. Furthermore, in vivo studies revealed that Green 1 was well tolerated in mice. Our findings suggest that a small change in the structure of colchicine has apparently changed the mechanism of action and lead to improved selectivity. This may lead to better selective treatments in cancer therapy.

  16. 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

  17. Sensitivity of Escherichia albertii, a potential foodborne pathogen, to food preservation treatments

    Science.gov (United States)

    Escherichia albertii is a potential foodborne pathogen because of its documented ability to cause diarrheal disease by producing attachment and effacement lesions. Its tolerance to food preservation treatments has not been investigated. Heat, acid, and pressure tolerance were determined for stationa...

  18. Accurate, noninvasive detection of Helicobacter pylori DNA from stool samples: potential usefulness for monitoring treatment.

    Science.gov (United States)

    Shuber, Anthony P; Ascaño, Jennifer J; Boynton, Kevin A; Mitchell, Anastasia; Frierson, Henry F; El-Rifai, Wa'el; Powell, Steven M

    2002-01-01

    A novel DNA assay demonstrating sensitive and accurate detection of Helicobacter pylori from stool samples is reported. Moreover, in three individuals tested for therapeutic response, the assay showed the disappearance of H. pylori DNA during treatment. Thus, this noninvasive molecular biology-based assay has the potential to be a powerful diagnostic tool given its ability to specifically identify H. pylori DNA.

  19. Accurate, Noninvasive Detection of Helicobacter pylori DNA from Stool Samples: Potential Usefulness for Monitoring Treatment

    OpenAIRE

    Shuber, Anthony P; Ascaño, Jennifer J.; Boynton, Kevin A.; Mitchell, Anastasia; Frierson, Henry F.; El-Rifai, Wa’el; Powell, Steven M

    2002-01-01

    A novel DNA assay demonstrating sensitive and accurate detection of Helicobacter pylori from stool samples is reported. Moreover, in three individuals tested for therapeutic response, the assay showed the disappearance of H. pylori DNA during treatment. Thus, this noninvasive molecular biology-based assay has the potential to be a powerful diagnostic tool given its ability to specifically identify H. pylori DNA.

  20. Bio-electro catalytic treatment of petroleum produced water: Influence of cathode potential upliftment.

    Science.gov (United States)

    Jain, Pratiksha; Srikanth, Sandipam; Kumar, Manoj; Sarma, Priyangshu M; Singh, M P; Lal, Banwari

    2016-11-01

    Treatment of petroleum produced water (PPW) was studied using bioelectrochemical system (BES) under uplifted cathode potential. The treatment efficiency in terms of COD and hydrocarbon removal was observed at 91.25% and 76.60% respectively, along with the reduction in TDS during BES operation under 400mV of cathode potential. There was also a reduction in concentration of sulfates, however, it was not significant at, since oxidative conditions are being maintained at anode. Improved oxidation of PPW at anode also resulted in good power output (-20.47mA) and also depicted improved fuel cell behaviour. The electrochemical analysis in terms of cyclic/linear sweep voltammetry also showed well correlation with the observed treatment efficiencies. The microbial dynamics of the BES after loading real field wastewater showed the dominance of species that are reported to be effective for petroleum crude oil degradation. PMID:27544915

  1. Metabolomics and its potential in diagnosis, prognosis and treatment of rheumatic diseases.

    Science.gov (United States)

    Smoleńska, Żaneta; Zdrojewski, Zbigniew

    2015-01-01

    The main aim of metabolomics is to make a comprehensive study of metabolites, the intermediates of biochemical processes in living organisms. Any pathophysiological mechanism caused by disease will inevitably lead to related changes in the concentrations of specific metabolites. In line with this, metabolomics offers a promising laboratory tool for the analysis of potential diagnostic biomarkers that may be used to assess susceptibility to a disease and to evaluate the prognosis and therapeutic response to treatment. Recent data have shown that metabolomics analysis in rheumatoid arthritis has made possible more efficient diagnosis, discrimination between patients with regard to disease activity, prediction of the response to a particular treatment approach, differentiation between rheumatic disease subtypes and greater understanding of the pathophysiology of this disease. Here we characterize metabolomics as a comprehensive laboratory tool and review its potential in the diagnosis, prognosis and treatment of rheumatic diseases such as rheumatoid arthritis.

  2. Enhanced biomethane potential from wheat straw by low temperature alkaline calcium hydroxide pre-treatment.

    Science.gov (United States)

    Reilly, Matthew; Dinsdale, Richard; Guwy, Alan

    2015-08-01

    A factorially designed experiment to examine the effectiveness of Ca(OH)2 pre-treatment, enzyme addition and particle size, on the mesophilic (35 °C) anaerobic digestion of wheat straw was conducted. Experiments used a 48 h pre-treatment with Ca(OH)2 7.4% (w/w), addition of Accellerase®-1500, with four particle sizes of wheat straw (1.25, 2, 3 and 10mm) and three digestion time periods (5, 15 and 30 days). By combining particle size reduction and Ca(OH)2 pre-treatment, the average methane potential was increased by 315% (from 48 NmL-CH4 g-VS(-1) to 202 NmL-CH4 g-VS(-1)) after 5 days of anaerobic digestion compared to the control. Enzyme addition or Ca(OH)2 pre-treatment with 3, 2 and 1.25 mm particle sizes had 30-day batch yields of between 301 and 335 NmL-CH4 g-VS(-1). Alkali pre-treatment of 3mm straw was shown to have the most potential as a cost effective pre-treatment and achieved 290 NmL-CH4 g-VS(-1), after only 15 days of digestion. PMID:25898087

  3. C1-esterase inhibitor treatment: preclinical safety aspects on the potential prothrombotic risk.

    Science.gov (United States)

    Schürmann, Daniel; Herzog, Eva; Raquet, Elmar; Nolte, Marc W; May, Frauke; Müller-Cohrs, Jochen; Björkqvist, Jenny; Dickneite, Gerhard; Pragst, Ingo

    2014-11-01

    Human plasma-derived C1-esterase inhibitor (C1-INH) is an efficacious and safe treatment for hereditary angioedema. However, thrombotic events in subjects treated with C1-INH at recommended or off-label, high doses have been reported. In this study, we addressed the potential prothrombotic risk of C1-INH treatment in high doses using a non-clinical rabbit model. Following intravenous infusion of C1-INH to rabbits at doses up to 800 IU/kg, the exposure and the pharmacodynamic efficacy of C1-INH in rabbits were confirmed by activity measurements of C1-esterase, and coagulation factors XIa and XIIa, respectively. Potential prothrombotic effects were assessed following induction of venous and arterial thrombosis using in vivo models of venous and arterial stasis, complemented by various in vitro assays of coagulation markers. Administration of C1-INH at doses up to 800 IU/kg did not potentiate thrombus formation during venous stasis. In contrast, inhibition of arterial occlusion was observed upon C1-INH administration when compared with isotonic saline treatment, indicating antithrombotic rather than prothrombotic activity of high dose C1-INH treatment in vivo. This was further confirmed in vitro by decreased thrombin generation, increased activated partial thromboplastin time, clotting time and clot formation time, and inhibition of platelet aggregation. No relevant changes in fibrinolysis or in the levels of thrombin-antithrombin complexes, and prothrombin fragment 1+2 were observed upon high dose C1-INH treatment. The data suggest that treatment of healthy rabbits with high doses of C1-INH could potentially inhibit coagulation and thrombus formation rather than induce a prothrombotic risk.

  4. Policy issues in space analogues

    Science.gov (United States)

    Auger, Robin N.; Facktor, Debra D.

    Space mission planning is increasingly focusing on destinations beyond Earth orbit. Advancements in technology will inevitably be required to enable long-duration human spaceflight missions, and breakthroughs in the policy arena will also be needed to achieve success in such missions. By exploring how policy issues have been addressed in analogous extreme environments, policymakers can develop a framework for addressing these issues as they apply to long-term human spaceflight. Policy issues that need to be addressed include: crew selection, training, organization, and activities, medical testing, illness, injury, and death; communication; legal accountability and liability; mission safety and risk management; and environmental contamination. This paper outlines the approach of a study underway by The George Washington University and ANSER to examine how these policy issues have been addressed in several analogues and how the experiences of these analogues can help formulate policies for long-duration human spaceflight missions. Analogues being studied include Antarctic bases, submarine voyages, undersea stations, Biosphere 2, and the U.S. Skylab and Russian Mir space stations.

  5. Dasatinib: the emerging evidence of its potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Sonya Haslam

    2005-03-01

    Full Text Available Sonya HaslamCore Medical Publishing, Mere House, Brook Street, Knutsford, Cheshire WA16 8GP, UKIntroduction: Current therapy options for chronic myeloid leukemia (CML include conventional chemotherapy, allogeneic stem cell transplant, interferon-alfa, and imatinib mesylate, which has recently achieved gold standard status. Although the majority of patients initially respond well to treatment with imatinib, wider clinical experience with this drug has resulted in the development of imatinib resistance being increasingly documented. There is therefore an unmet medical need for novel therapies to override imatinib resistance in CML.Aims: This review summarizes the emerging evidence for the potential use of dasatinib in the treatment of imatinib-resistant CML. Disease and treatment: Dasatinib is a novel small molecule that has shown potent antileukemic activity in imatinib-resistant cell lines, malignant marrow cells isolated from patients with imatinib-resistant CML, and in mouse xenograft models of imatinib-resistant CML. Preliminary data from an initial phase I dose escalation trial have been encouraging, indicating that dasatinib is generally well tolerated and produces hematologic and cytogenetic responses in patients with imatinib-resistant CML in all phases of the disease. The maximum tolerated dose (MTD has not yet been reached, and dose escalation continues to determine the dose range that yields optimal results.Profile: Although dasatinib is still in the early stages of development, the potential impact of this molecule on the treatment of CML could be revolutionary, not only providing a much needed treatment option for patients with imatinib-resistant CML, but also, combined with imatinib, could possibly prove useful in delaying the onset of resistance to treatment. Furthermore, combined with other agents active in CML, dasatinib could have potential utility in purging residual leukemic cells in patients whose disease is controlled by

  6. [Dmt(1)]DALDA analogues with enhanced μ opioid agonist potency and with a mixed μ/κ opioid activity profile.

    Science.gov (United States)

    Bai, Longxiang; Li, Ziyuan; Chen, Jiajia; Chung, Nga N; Wilkes, Brian C; Li, Tingyou; Schiller, Peter W

    2014-04-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity, were prepared by replacing Phe(3) with various 2',6'-dialkylated Phe analogues, including 2',6'-dimethylphenylalanine (Dmp), 2',4',6'-trimethylphenylalanine (Tmp), 2'-isopropyl-6'-methylphenylalanine (Imp) and 2'-ethyl-6'-methylphenylalanine (Emp), or with the bulky amino acids 3'-(1-naphthyl)alanine (1-Nal), 3'-(2-naphthyl)alanine (2-Nal) or Trp. Several compounds showed significantly increased μ agonist potency, retained μ receptor selectivity and are of interest as drug candidates for neuropathic pain treatment. Surprisingly, the Dmp(3)-, Imp(3)-, Emp(3)- and 1-Nal(3)-containing analogues showed much increased κ receptor binding affinity and had mixed μ/κ properties. In these cases, molecular dynamics studies indicated conformational preorganization of the unbound peptide ligands due to rotational restriction around the C(β)C(γ) bond of the Xxx(3) residue, in correlation with the observed κ receptor binding enhancement. Compounds with a mixed μ/κ opioid activity profile are known to have therapeutic potential for treatment of cocaine abuse.

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Haque, Md Mominul; Smith, Warren T; Wong, Danny K Y

    2015-01-01

    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(-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.

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

    International Nuclear Information System (INIS)

    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

  11. 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.

  12. 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

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

    Institute of Scientific and Technical Information of China (English)

    MA Zhan-Yun; FENG Peng; GAO Qing-Xian; LU Yan-Na; LIU Jun-Rong; LI Wen-Tao

    2015-01-01

    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.

  14. Long term in-line sludge storage in wastewater treatment plants: the potential for phosphorus release.

    Science.gov (United States)

    Johannessen, Erik; Eikum, Arild Schanke; Krogstad, Tore

    2012-12-01

    Phosphorus removal in on-site wastewater treatment plants is normally obtained by chemical precipitation. Aluminium-based chemicals are the favoured coagulants as they are not affected by redox potential. On-site wastewater treatment package plants do not have separate sludge treatment facilities, and sludge is normally collected on an annual basis. This can potentially increase the risk of phosphorus release into the water phase, subsequently reducing treatment efficiency. This study aimed to detect release of phosphorus as a result of chemical and biological processes. Variables in the study were time, aluminium dosage and pH. Wastewater sludge was monitored for 46 weeks to investigate the different mechanisms of phosphorus release and the longevity of the aluminium treatment involving varying aluminium dosages. Phosphorus compounds were analysed based on a modified Psenner sequential fractionation method. Both pH and aluminium dosage affect the longevity of the phosphorus retention of chemically precipitated wastewater sludge, where sufficient longevity is obtained with pH control and increased aluminium dosages. Chemical dosages similar to what is considered normal levels are sufficient to retain the phosphorus in the sludge for annual sludge collection intervals. Release of soluble phosphorus was attributed to microbial activity and crystallization of Al-hydroxide complexes. PMID:23437673

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Mars Methane Analogue Mission (M3): Near Subsurface Electromagnetic Techniques and Analysis

    Science.gov (United States)

    Boivin, A.; Samson, C.; Holladay, J. S.; Cloutis, E. A.; Ernst, R. E.

    2012-03-01

    As part of the Canadian Space Agency's Mars Methane Analogue Mission, a micro-rover mission, an Electromagnetic Induction Sounder (EMIS) was used with the goal of demonstrating its value as a potential science instrument onboard future rovers.

  1. Potential of cystamine and cysteamine in the treatment of neurodegenerative diseases.

    Science.gov (United States)

    Gibrat, C; Cicchetti, F

    2011-03-30

    Neurodegenerative disorders are a subset of disabling pathologies characterized, in part, by a progressive and specific loss of certain brain cell populations. Current therapeutic approaches for the treatment of these disorders are mainly designed towards symptom management and do not manifestly block their typified neuronal loss. However, research conducted over the past decade has reflected the increasing interest and need to find disease-modifying molecules. Among the several neuroprotective agents emerging from experimental animal work, cystamine, as well as its reduced form cysteamine, have been identified as potential candidate drugs. Given the significant benefits observed in a Huntington's disease (HD) model, cysteamine has recently leaped to clinical trial. Here, we review the beneficial properties of these compounds as reported in animal studies, their mechanistic underpinnings, and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically for HD and Parkinson's disease (PD). PMID:21111020

  2. Algal wastewater treatment and biomass producing potential: nutrient removal efficiency and cell physiological responses

    OpenAIRE

    Samorì, Giulia

    2012-01-01

    Microalgae are sun - light cell factories that convert carbon dioxide to biofuels, foods, feeds, and other bioproducts. The concept of microalgae cultivation as an integrated system in wastewater treatment has optimized the potential of the microalgae - based biofuel production. These microorganisms contains lipids, polysaccharides, proteins, pigments and other cell compounds, and their biomass can provide different kinds of biofuels such as biodiesel, biomethane and ethanol. The algal biomas...

  3. Potential of energy and nutrient recovery from biodegradable waste by co-treatment in Lithuania

    OpenAIRE

    Havukainen, Jouni; Zavarauskas, Kestutis; Denafas, Gintaras; Luoranen, Mika; Kahiluoto, Helena; Kuisma, Miia; Horttanainen, Mika

    2012-01-01

    Biodegradable waste quantities in Lithuania and their potential for the co-treatment in renewable energy and organic fertilizer production are investigated. Two scenarios are formulated to study the differences of the amounts of obtainable energy and fertilizers between different ways of utilization. In the first scenario, only digestion is used, and in the second scenario, other materials than straw are digested, and straw and the solid fraction of sewage sludge digestate are combusted. As a...

  4. Design, synthesis and characterisation of gurmarin and melanocortin analogues of gurmarin

    DEFF Research Database (Denmark)

    Eliasen, Rasmus

    In this Ph.D. project the possibility of grafting melanocortin receptor binding sequences into the inhibitor cystine knotted peptide gurmarin was investigated. The goal of designing these analogues was to produce highly stable peptide agonists with potential for obesity treatment Inhibitor cystine...... knotted peptides are a group of peptides found in a variety of plant and animal species. They all contain six cysteines forming three disulphides which determine their tertiary structure and provide them with exceptional proteolytic stability. It has been demonstrated that these peptides can be used...... it regulates appetite and energy expenditure. The melanocortin receptors are activated by peptides containing a His-Phe-Arg-Trp tetrapeptide sequence. Consequently, inhibitor cystine knotted peptides in which this tetrapeptide are grafted could provide novel appetite regulating peptides for the treatment...

  5. 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.

  6. Cannabinoids As Potential Treatment for Chemotherapy-Induced Nausea and Vomiting.

    Science.gov (United States)

    Rock, Erin M; Parker, Linda A

    2016-01-01

    Despite the advent of classic anti-emetics, chemotherapy-induced nausea is still problematic, with vomiting being somewhat better managed in the clinic. If post-treatment nausea and vomiting are not properly controlled, anticipatory nausea-a conditioned response to the contextual cues associated with illness-inducing chemotherapy-can develop. Once it develops, anticipatory nausea is refractive to current anti-emetics, highlighting the need for alternative treatment options. One of the first documented medicinal uses of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was for the treatment of chemotherapy-induced nausea and vomiting (CINV), and recent evidence is accumulating to suggest a role for the endocannabinoid system in modulating CINV. Here, we review studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system in human patients and pre-clinical animal models of nausea and vomiting. PMID:27507945

  7. 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.

  8. 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.

  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. PMID:27128189

  10. Topical treatment in vitiligo and the potential uses of new drug delivery systems

    Directory of Open Access Journals (Sweden)

    Garg Bhawna

    2010-01-01

    Full Text Available Vitiligo is a psychologically devastating condition. Topical therapy is employed as first-line treatment in localized vitiligo. Currently, several topical agents are available in many forms viz. methoxsalen (solution and cream, trioxsalen (solution, corticosteroids (gel, cream, ointment and solution and calcineurin inhibitors (ointment and cream. Although topical therapy has an important position in vitiligo treatment, side-effects or poor efficacy affect their utility and patient compliance. Novel drug delivery strategies can play a pivotal role in improving the topical delivery of various drugs by enhancing their epidermal localization with a concomitant reduction in their side-effects and improving their effectiveness. The current review emphasizes the potential of various phospholipid based carriers viz. liposomes, transferosomes, ethosomes, lipid emulsions, solid lipid nanoparticles and organogels in optimizing and enhancing the topical delivery of anti-vitiligo agents, whilst reducing the side effects of drugs commonly used in its topical treatment.

  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.

  12. FUNCTION GENERATOR FOR ANALOGUE COMPUTERS

    Science.gov (United States)

    Skramstad, H.K.; Wright, J.H.; Taback, L.

    1961-12-12

    An improved analogue computer is designed which can be used to determine the final ground position of radioactive fallout particles in an atomic cloud. The computer determines the fallout pattern on the basis of known wind velocity and direction at various altitudes, and intensity of radioactivity in the mushroom cloud as a function of particle size and initial height in the cloud. The output is then displayed on a cathode-ray tube so that the average or total luminance of the tube screen at any point represents the intensity of radioactive fallout at the geographical location represented by that point. (AEC)

  13. Effects of melatonin and its analogues on neural stem cells.

    Science.gov (United States)

    Chu, Jiaqi; Tu, Yalin; Chen, Jingkao; Tan, Dunxian; Liu, Xingguo; Pi, Rongbiao

    2016-01-15

    Neural stem cells (NSCs) are multipotent cells which are capable of self-replication and differentiation into neurons, astrocytes or oligodendrocytes in the central nervous system (CNS). NSCs are found in two main regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ). The recent discovery of NSCs in the adult mammalian brain has fostered a plethora of translational and preclinical studies to investigate novel approaches for the therapy of neurodegenerative diseases. Melatonin is the major secretory product synthesized and secreted by the pineal gland and shows both a wide distribution within phylogenetically distant organisms from bacteria to humans and a great functional versatility. Recently, accumulated experimental evidence showed that melatonin plays an important role in NSCs, including its proliferation, differentiation and survival, which are modulated by many factors including MAPK/ERK signaling pathway, histone acetylation, neurotrophic factors, transcription factors, and apoptotic genes. The purpose of this review is to summarize the beneficial effects of melatonin on NSCs and further to discuss the potential usage of melatonin and its derivatives or analogues in the treatment of CNS neurodegenerative diseases. PMID:26499395

  14. What Can We Learn From Analogue Experiments?

    CERN Document Server

    Thebault, Karim P Y

    2016-01-01

    In 1981 Unruh proposed that fluid mechanical experiments could be used to probe key aspects of the quantum phenomenology of black holes. In particular, he claimed that an analogue to Hawking radiation could be created within a fluid mechanical `dumb hole', with the event horizon replaced by a sonic horizon. Since then an entire sub-field of `analogue gravity' has been created. In 2016 Steinhauer reported the experimental observation of quantum Hawking radiation and its entanglement in a Bose-Einstein condensate analogue black hole. What can we learn from such analogue experiments? In particular, in what sense can they provide evidence of novel phenomena such as black hole Hawking radiation?

  15. Potential Use of Polyacrylamide Encapsulation for Treatment of Petroleum Drilling Cuttings and Hydrocarbon Contaminated Soil

    Directory of Open Access Journals (Sweden)

    Randy H. Adams

    2011-07-01

    Full Text Available Mineral soil of alluvial origin, contaminated with diesel+lubricating oil (1:2, was treated with a commercial polyacrylamide product at 100 % of the distributer recommended dosage, producing a reduction in hydrocarbon concentration (EPA 9074 of 76 % that remained stable during the study period (38 days and even after thermal treatment (60 ºC, 18 hrs.. Increasing the dosage to 150 % did not improve the treatment results, but repeating the treatment (at 100 % resulted in a slight additional reduction (4 %. Similar results were obtained with oil-based drilling cuttings (~60 % reduction at both 100 % and 150 %. Pre-drying of the drilling cuttings prior to treatment did not improve the hydrocarbon reduction, but it did produce smaller, potentially more stable aggregates (0.5 – 1-0 mm in diameter. The treatment of organic soil resulted in a similar reduction in hydrocarbon concentration (65 % and a reduction of acute toxicity (Microtox to below background levels, however this effect was not stable. An additional application (including mixing of the polyacrylamide product resulted in partial disintegration of the organic fibres and release of the stabilized hydrocarbons, measuring an overall increase in hydrocarbon concentration of 19 %.

  16. 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.

  17. The Valles natural analogue project

    Energy Technology Data Exchange (ETDEWEB)

    Stockman, H.; Krumhansl, J.; Ho, C. [Sandia National Labs., Albuquerque, NM (United States); McConnell, V. [Alaska Univ., Fairbanks, AK (United States). Geophysical Inst.

    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 {sup 39}Ar/{sup 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.

  18. A Sleeping Beauty DNA transposon-based genetic sensor for functional screening of vitamin D3 analogues

    DEFF Research Database (Denmark)

    Staunstrup, Nicklas Heine; Sharma, Nynne; Bak, Rasmus Otkjær;

    2011-01-01

    Analogues of vitamin D3 are extensively used in the treatment of various illnesses, such as osteoporosis, inflammatory skin diseases, and cancer. Functional testing of new vitamin D3 analogues and formulations for improved systemic and topical administration is supported by sensitive screening me...

  19. Current european regulatory perspectives on insulin analogues

    Directory of Open Access Journals (Sweden)

    Enzmann Harald G

    2011-07-01

    Full Text Available Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions.

  20. Evolving a polymerase for hydrophobic base analogues.

    Science.gov (United States)

    Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

    2009-10-21

    Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity. PMID:19778048

  1. Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder.

    Science.gov (United States)

    Agorastos, Agorastos; Linthorst, Astrid C E

    2016-08-01

    Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune, and autonomic system, similar to chronic stress and may play a central role in the development of stress-related disorders. Recent articles have focused on the role of sleep and circadian disruption in the pathophysiology of posttraumatic stress disorder (PTSD), suggesting that chronodisruption plays a causal role in PTSD development. Direct and indirect human and animal PTSD research suggests circadian system-linked neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Recent experimental findings also support a specific role of the fundamental synchronizing pineal hormone melatonin in mechanisms of sleep, cognition and memory, metabolism, pain, neuroimmunomodulation, stress endocrinology and physiology, circadian gene expression, oxidative stress and epigenetics, all processes affected in PTSD. In the current paper, we review available literature underpinning a potentially beneficiary role of an add-on melatonergic treatment in PTSD pathophysiology and PTSD-related symptoms. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. We conclude that adjuvant melatonergic treatment could provide a potentially promising treatment strategy in the management of PTSD and especially PTSD-related syndromes and comorbidities. Rigorous preclinical and clinical studies are needed to validate this hypothesis. PMID:27061919

  2. Characterization of aluminium-based water treatment residual for potential phosphorus removal in engineered wetlands

    Energy Technology Data Exchange (ETDEWEB)

    Babatunde, A.O., E-mail: akintunde.babatunde@ucd.i [Centre for Water Resources Research, School of Architecture, Landscape and Civil Engineering, Newstead Building, University College Dublin, Belfield, Dublin 4 (Ireland); Zhao, Y.Q. [Centre for Water Resources Research, School of Architecture, Landscape and Civil Engineering, Newstead Building, University College Dublin, Belfield, Dublin 4 (Ireland); Burke, A.M. [Department of Chemistry, University College Cork, Cork (Ireland); Morris, M.A.; Hanrahan, J.P. [Environmental Research Institute (ERI), University College Cork, Lee Road, Cork (Ireland)

    2009-10-15

    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{sup 2} g{sup -1} to 41.4 m{sup 2} g{sup -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{sup -1} to 0.140 dS m{sup -1} respectively, showing that it should support plant growth. Batch tests showed adsorption maxima of 31.9 mg P g{sup -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 wetlandsexclamation

  3. Conversion of sewage treatment plants on sludge digestion. Energetic and economic optimization potential

    International Nuclear Information System (INIS)

    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.

  4. Survey of potential improvements during the course of the radiotherapy treatment. A patient questionnaire

    International Nuclear Information System (INIS)

    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

  5. Research progress of somatostatin analogues in the treatment of Cushing's disease%生长抑素类似物治疗库欣病的研究进展

    Institute of Scientific and Technical Information of China (English)

    周逸亭; 叶红英

    2012-01-01

    垂体促肾上腺皮质激素(ACTH)瘤表达生长抑素受体(SSTR),主要亚型为SSTR2和SSTR5.SSTR2表达可因皮质醇作用而下调.临床上常用的生长抑素类似物奥曲肽和兰瑞肽主要作用于SSTR2,对库欣病无明显治疗作用.帕瑞肽是作用于SSTR多亚型的新型生长抑素类似物,基础和临床研究证实其可有效降低库欣病患者血、尿皮质醇,改善症状,为库欣病带来新的治疗前景.%Somatostatin receptors (SSTR) are expressed in adreno-corticotropic-hormone-secreting adenoma,which are mainly SSTR2 and SSTR5.SSTR2 can be downregulated by cortisol.Octreotide and lanreotide are the clinically approved somatostatin analogues which mainly bind to SSTR2 and show no effect on Cushing's disease.Pasireotide is a novel multi-receptor-targeted somatostatin analogue.It has been proved by basic experiments and clinical trials that pasireotide can efficiently decrease serum and urine cortisol level and improve symptoms,which holds promise for Cushing's disease.

  6. 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.

  7. Idelalisib for the treatment of indolent non-Hodgkin lymphoma: a review of its clinical potential.

    Science.gov (United States)

    Barrientos, Jacqueline C

    2016-01-01

    Idelalisib is a first-in-class, oral, selective phosphatidylinositol 3-kinase δ inhibitor that offers a chemotherapy-free option for patients with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Clinical trials in iNHL have evaluated idelalisib as monotherapy and as combination therapy with rituximab, bendamustine, and rituximab + bendamustine. When administered to heavily pretreated patients with R/R iNHL, idelalisib monotherapy or combination therapy showed durable antitumor activity accompanied by sustained or improved quality-of-life outcomes. Idelalisib has an acceptable safety profile; however, serious or fatal diarrhea/colitis, hepatoxicity, pneumonitis, and intestinal perforation have occurred in treated patients. Selective inhibition of phosphatidylinositol 3-kinase δ with idelalisib is a valuable addition to available treatment options for patients with iNHL, many of whom do not respond to or cannot tolerate chemoimmunotherapy. Two Phase III, randomized, placebo-controlled trials of idelalisib as combination therapy with rituximab or bendamustine + rituximab and a Phase I trial of idelalisib in combination with the Bruton's tyrosine kinase inhibitor ONO/GS-4059 in R/R B-cell malignancies are currently ongoing. A Phase III monotherapy trial in previously treated follicular lymphoma or small lymphocytic lymphoma is planned. The development of other kinase inhibitors for the treatment of iNHL raises the potential for new treatment combinations. Additional research is needed to determine optimal therapy (monotherapy vs combination regimens), treatment sequencing, and long-term management.

  8. Potential utility of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism: a case report

    Science.gov (United States)

    Sato, Takeshi; Muroya, Koji; Hanakawa, Junko; Yamashita, Sumimasa; Nozawa, Kumiko; Masudo, Katsuhiko; Yamakawa, Tadashi; Asakura, Yumi; Hasegawa, Tomonobu; Adachi, Masanori

    2016-01-01

    Abstract. We report a Japanese pedigree with familial primary hyperparathyroidism due to a CDC73 mutation. To our knowledge, this is the first report of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism. The proband had severe psychomotor retardation and received laryngotracheal separation surgery. At 19 yr of age, he developed acute pancreatitis. Hypercalcemia (12.2–13.8 mg/dL), elevated levels of intact PTH (86–160 pg/mL), and a tumor detected upon neck ultrasonography led to the diagnosis of primary hyperparathyroidism. Family history and biochemical examinations revealed that three family members (the proband’s mother, elder brother, and maternal grandfather) had primary hyperparathyroidism. We identified a novel heterozygous mutation, c.240delT, p.Glu81Lysfs*28, in the CDC73 gene in three affected family members, excluding the proband’s elder brother who refused genetic testing. Parathyroidectomy for the proband was considered as high-risk, because the tumor was located close to the tracheostomy orifice. After receiving approval from the institutional review board and obtaining the consent, we initiated cinacalcet treatment. At 22 yr of age, treatment with 100 mg of cinacalcet maintained serum calcium levels below 11.0 mg/dL with no apparent side effects. Our report presents the potential efficacy of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism, in particularly inoperative cases. PMID:27507909

  9. Potential utility of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism: a case report.

    Science.gov (United States)

    Sato, Takeshi; Muroya, Koji; Hanakawa, Junko; Yamashita, Sumimasa; Nozawa, Kumiko; Masudo, Katsuhiko; Yamakawa, Tadashi; Asakura, Yumi; Hasegawa, Tomonobu; Adachi, Masanori

    2016-07-01

    We report a Japanese pedigree with familial primary hyperparathyroidism due to a CDC73 mutation. To our knowledge, this is the first report of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism. The proband had severe psychomotor retardation and received laryngotracheal separation surgery. At 19 yr of age, he developed acute pancreatitis. Hypercalcemia (12.2-13.8 mg/dL), elevated levels of intact PTH (86-160 pg/mL), and a tumor detected upon neck ultrasonography led to the diagnosis of primary hyperparathyroidism. Family history and biochemical examinations revealed that three family members (the proband's mother, elder brother, and maternal grandfather) had primary hyperparathyroidism. We identified a novel heterozygous mutation, c.240delT, p.Glu81Lysfs*28, in the CDC73 gene in three affected family members, excluding the proband's elder brother who refused genetic testing. Parathyroidectomy for the proband was considered as high-risk, because the tumor was located close to the tracheostomy orifice. After receiving approval from the institutional review board and obtaining the consent, we initiated cinacalcet treatment. At 22 yr of age, treatment with 100 mg of cinacalcet maintained serum calcium levels below 11.0 mg/dL with no apparent side effects. Our report presents the potential efficacy of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism, in particularly inoperative cases. PMID:27507909

  10. 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

  11. Potential of targeted drug delivery system for the treatment of bone metastasis.

    Science.gov (United States)

    Vinay, Raichur; KusumDevi, V

    2016-01-01

    Bone metastasis is a devastating complication of cancer that requires an immediate attention. Although our understanding of the metastatic process has improved over the years, yet a number of questions still remain unanswered, and more research is required for complete understanding of the skeletal consequences of metastasis. Furthermore, as no effective treatments are available for some of the most common skeleton disorders such as arthritis, osteoarthritis, osteosarcoma and metastatic bone cancer, there is an urgent need to develop new drugs and drug delivery systems for safe and efficient clinical treatments. Hence this article describes the potential of targeted delivery platforms aimed specifically at bone metastasized tumors. The review gives a brief understanding of the proposed mechanisms of metastasis and focuses primarily on the targeting moieties such as bisphosphonates, which represent the current gold standard in bone metastasis therapies. Special focus has been given to the targeted nanoparticulate systems for treating bone metastasis and its future. Also highlighted are some of the therapeutic targets that can be exploited for designing therapies for bone metastasis. Some of the patented molecules for bone metastasis prevention and treatment have also been discussed. Recently proposed HIFU-CHEM, which utilizes High Intensity Focused ultrasound (HIFU) guided by MRI in combination with temperature-sensitive nanomedicines has also been briefed. The study has been concluded with a focus on the innovations requiring an immediate attention that could improve the treatment modality of bone metastasis.

  12. CO2 Capture with Enzyme Synthetic Analogue

    Energy Technology Data Exchange (ETDEWEB)

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  13. 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.

  14. Surgical treatment for epilepsy: the potential gap between evidence and practice.

    Science.gov (United States)

    Jetté, Nathalie; Sander, Josemir W; Keezer, Mark R

    2016-08-01

    Findings from randomised controlled trials, along with more than 100 case series and observational studies, support the efficacy and safety of resective surgery and, more recently, non-resective surgical interventions for the treatment of drug-resistant epilepsy in appropriately selected individuals. There is an argument that epilepsy surgery remains underused, but the evidence to support this assertion is at times unclear. Results from longitudinal studies show a stagnant or declining rate of epilepsy surgery over time, despite the evidence and guidelines supporting its use. Some suggest that this stagnation is due to a decreasing pool of eligible surgical candidates, whereas others emphasise the numerous barriers to epilepsy surgery. Strategies exist to increase access to surgery and to improve communication about the effectiveness of this potentially life-changing procedure. Further investigation into the nature and causes of the presumed underuse of epilepsy surgery and the elaboration of strategies to address this treatment gap are necessary and pressing. PMID:27478955

  15. 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.

  16. 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

  17. Drug-likeness of Phytic Acid and Its Analogues

    OpenAIRE

    Joy, Amitha; Balaji, S.

    2015-01-01

    Inositol hexakisphosphate is known to be the phosphorous reserve in plants particularly in the seeds. Though it has been known for its antinutrient properties for many years, recent research shed light to reveal it as a novel anticancer agent. Hence the present study investigates the drug-likeness of phytic acid and its analogues through bioinformatics methods. Two potential cancer drug targets such as mitogen activated kinase and inositol 1,4,5-triphosphate receptor are included in the study...

  18. 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.

  19. 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

  20. Axitinib: The evidence of its potential in the treatment of advanced thyroid cancer

    Directory of Open Access Journals (Sweden)

    Hari A Deshpande, Scott Gettinger

    2009-06-01

    Full Text Available Hari A Deshpande1, Scott Gettinger1, Julie Ann Sosa21Yale Cancer Center, Department of Medical Oncology, 2Division of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT, USAIntroduction: Thyroid cancer is a rare disease with an incidence of around 37,000 cases per year. However, its incidence is rising faster than many other cancers and for men this disease ranks highest overall in the rate of increase (2.4% annual increase in cancer deaths. As the number of radioactive iodine-resistant thyroid cancers increases, the need for newer treatments has become more important. Axitinib is one of many new small molecule inhibitors of growth factor receptors that have shown promise in the treatment of many cancers. It targets the vascular endothelial growth factor receptors 1, 2 and 3.Aims: The goal of this article is to review the published evidence for the use of axitinib in the treatment of thyroid cancer and define its therapeutic potential. Evidence review: The major evidence of axitinib activity has appeared in meeting report abstracts. One phase II study has been published. This included patients with any histological type of thyroid cancer that was not amenable to treatment with radioactive iodine. Clinical potential: To date, in phase II clinical studies axitinib has demonstrated antitumor activity in advanced refractory thyroid cancer. As a monotherapy it resulted in a 30% response rate with another 38% of patients having stable disease. Axitinib appears to have a good tolerability profile, with hypertension being the most common grade 3 or greater side effect. Keywords: axitinib, thyroid cancer, vascular endothelial growth factor receptor

  1. Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

    Directory of Open Access Journals (Sweden)

    Michelle Visagie

    Full Text Available 2-Methoxyestradiol (2ME2 is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.

  2. Pre-treatment and ethanol fermentation potential of olive pulp at different dry matter concentrations

    DEFF Research Database (Denmark)

    Haagensen, Frank Drøscher; Skiadas, Ioannis V.; Gavala, Hariklia N.;

    2009-01-01

    potential of the olive pulp, which is the semi solid residue generated from the two-phase processing of the olives for olive oil production. Wet oxidation and enzymatic hydrolysis have been applied aiming at the enhancement of carbohydrates' bioavailability. Different concentrations of enzymes and enzymatic......, implying that wet oxidation is not a recommended pre-treatment process for olive pulp at the conditions tested. It was also showed that increased dry matter concentration did not have a negative effect on the release of sugars, indicating that the cellulose and xylan content of the olive pulp is relatively...

  3. Importance of biological systems in industrial waste treatment potential application to the space station

    Science.gov (United States)

    Revis, Nathaniel; Holdsworth, George

    1990-01-01

    In addition to having applications for waste management issues on planet Earth, microbial systems have application in reducing waste volumes aboard spacecraft. A candidate for such an application is the space station. Many of the planned experiments generate aqueous waste. To recycle air and water the contaminants from previous experiments must be removed before the air and water can be used for other experiments. This can be achieved using microorganisms in a bioreactor. Potential bioreactors (inorganics, organics, and etchants) are discussed. Current technologies that may be applied to waste treatment are described. Examples of how biological systems may be used in treating waste on the space station.

  4. Strategy and methodology of dynamical analogue prediction

    Institute of Scientific and Technical Information of China (English)

    REN; HongLi; CHOU; JiFan

    2007-01-01

    In order to effectively improve numerical prediction level by using current models and data, the strategy and methodology of dynamical analogue prediction (DAP) is deeply studied in the present paper. A new idea to predict the prediction errors of dynamical model on the basis of historical analogue information is put forward so as to transform the dynamical prediction problem into the estimation problem of prediction errors. In terms of such an idea, a new prediction method of final analogue correction of errors (FACE) is developed. Furthermore, the FACE is applied to extra-seasonal prediction experiments on an operational atmosphere-ocean coupled general circulation model. Prediction results of summer mean circulation and total precipitation show that the FACE can to some extent reduce prediction errors, recover prediction variances, and improve prediction skills. Besides, sensitive experiments also show that predictions based on the FACE are evidently influenced by the number of analogues, analogue-selected variables and analogy metric.

  5. Improved Aptamers for the Diagnosis and Potential Treatment of HER2-Positive Cancer

    Science.gov (United States)

    Gijs, Marlies; Penner, Gregory; Blackler, Garth B.; Impens, Nathalie R.E.N.; Baatout, Sarah; Luxen, André; Aerts, An M.

    2016-01-01

    Aptamers provide a potential source of alternative targeting molecules for existing antibody diagnostics and therapeutics. In this work, we selected novel DNA aptamers targeting the HER2 receptor by an adherent whole-cell SELEX approach. Individual aptamers were identified by next generation sequencing and bioinformatics analysis. Two aptamers, HeA2_1 and HeA2_3, were shown to bind the HER2 protein with affinities in the nanomolar range. In addition, both aptamers were able to bind with high specificity to HER2-overexpressing cells and HER2-positive tumor tissue samples. Furthermore, we demonstrated that aptamer HeA2_3 is being internalized into cancer cells and has an inhibitory effect on cancer cell growth and viability. In the end, we selected novel DNA aptamers with great potential for the diagnosis and possible treatment of HER2-positive cancer. PMID:27213406

  6. Improved Aptamers for the Diagnosis and Potential Treatment of HER2-Positive Cancer

    Directory of Open Access Journals (Sweden)

    Marlies Gijs

    2016-05-01

    Full Text Available Aptamers provide a potential source of alternative targeting molecules for existing antibody diagnostics and therapeutics. In this work, we selected novel DNA aptamers targeting the HER2 receptor by an adherent whole-cell SELEX approach. Individual aptamers were identified by next generation sequencing and bioinformatics analysis. Two aptamers, HeA2_1 and HeA2_3, were shown to bind the HER2 protein with affinities in the nanomolar range. In addition, both aptamers were able to bind with high specificity to HER2-overexpressing cells and HER2-positive tumor tissue samples. Furthermore, we demonstrated that aptamer HeA2_3 is being internalized into cancer cells and has an inhibitory effect on cancer cell growth and viability. In the end, we selected novel DNA aptamers with great potential for the diagnosis and possible treatment of HER2-positive cancer.

  7. Clostridium perfringens enterotoxin as a potential drug for intravesical treatment of bladder cancer.

    Science.gov (United States)

    Gabig, Theodore G; Waltzer, Wayne C; Whyard, Terry; Romanov, Victor

    2016-09-16

    phosphorylation status of EphA2 and Src after C-CPE treatment and found changes in expression and phosphorylated status of these regulatory molecules. These observations show that after additional preclinical studies CPE and C-CPE in combinations with other drugs can be considered as a potential modalities for intravesical treatment of BC because of its ability to effectively destroy BC cells expressing claudin 4 and low toxicity against normal urothelium. PMID:27520378

  8. 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. PMID:27108702

  9. Mitochondria-Targeted Analogues of Metformin Exhibit Enhanced Antiproliferative and Radiosensitizing Effects in Pancreatic Cancer Cells.

    Science.gov (United States)

    Cheng, Gang; Zielonka, Jacek; Ouari, Olivier; Lopez, Marcos; McAllister, Donna; Boyle, Kathleen; Barrios, Christy S; Weber, James J; Johnson, Bryon D; Hardy, Micael; Dwinell, Michael B; Kalyanaraman, Balaraman

    2016-07-01

    Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its mitochondria-targeting potential by attaching a positively charged lipophilic substituent would enhance the antitumor activity of Met. In pursuit of this question, we synthesized a set of mitochondria-targeted Met analogues (Mito-Mets) with varying alkyl chain lengths containing a triphenylphosphonium cation (TPP(+)). In particular, the analogue Mito-Met10, synthesized by attaching TPP(+) to Met via a 10-carbon aliphatic side chain, was nearly 1,000 times more efficacious than Met at inhibiting cell proliferation in pancreatic ductal adenocarcinoma (PDAC). Notably, in PDAC cells, Mito-Met10 potently inhibited mitochondrial complex I, stimulating superoxide and AMPK activation, but had no effect in nontransformed control cells. Moreover, Mito-Met10 potently triggered G1 cell-cycle phase arrest in PDAC cells, enhanced their radiosensitivity, and more potently abrogated PDAC growth in preclinical mouse models, compared with Met. Collectively, our findings show how improving the mitochondrial targeting of Met enhances its anticancer activities, including aggressive cancers like PDAC in great need of more effective therapeutic options. Cancer Res; 76(13); 3904-15. ©2016 AACR. PMID:27216187

  10. A Study Of The Potential For Digital Radiographic Data Acquisition For Radiation Therapy Treatment Planning

    Science.gov (United States)

    Edwards, M.; Keller, J.; Hobson, G.

    1983-12-01

    While the quantitative nature of digital fluroscopic and digital radiographic imaging would seem to make possible many radiotherapeutic applications, significant problems must first be solved. The purpose of this study is to examine the potential benefits of digital imaging in radiation therapy, identify what problems must be solved to attain these benefits, and attempt to make some assessment as to the relative merits of developing such technologies. Among the potential benefits are ability to do contrast-subtraction studies for tumor and/or normal structure localization and portal placement, digital simulation of portal placement and treatment delivery, spatial localization and digitization of inhomogeneity boundaries, spatial localization and digitization of brachytherapy sources, and quantitative inhomogeneity acquisition for dosimetry calculations. Significant problems which must be solved include image receptor size limitations, image acquisition geometry related spatial distortion, three dimensional region calculation from limited views, and physical interpretation of digital image grey levels. Maximal benefits of digital imaging in radiation oncology is likely to be obtained by the development of large area image receptors for use in therapy simulators with direct data link to a combined image-analysis/treatment planning computer.

  11. 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 Aβ1–42 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

  12. β-Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: role in the regulation of response to somatostatin analogue treatment in patients with acromegaly.

    Science.gov (United States)

    Gatto, Federico; Feelders, Richard; van der Pas, Rob; Kros, Johan M; Dogan, Fadime; van Koetsveld, Peter M; van der Lelij, Aart-Jan; Neggers, Sebastian J C M M; Minuto, Francesco; de Herder, Wouter; Lamberts, Steven W J; Ferone, Diego; Hofland, Leo J

    2013-12-01

    Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK)2 and β-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. Our aim was to characterize GRK2 and β-arrestins expression in different pituitary adenomas and to investigate their potential role in the response to somatostatin analog (SSA) treatment in GH-secreting adenomas (GHomas). We evaluated mRNA expression of multiple SSTRs, GRK2, β-arrestin 1, and β-arrestin 2 in 41 pituitary adenomas (31 GHomas, 6 nonfunctioning [NFPAs], and 4 prolactinomas [PRLomas]). Within the GHomas group, mRNA data were correlated with the in vivo response to an acute octreotide test and with the GH-lowering effect of SSA in cultured primary cells. β-Arrestin 1 expression was low in all 3 adenoma histotypes. However, its expression was significantly lower in GHomas and PRLomas, compared with NFPAs (P affect GRK2 and β-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. Noteworthy, β-arrestin 1 was significantly lower (P < .05) in tumors responsive to octreotide treatment in vitro, whereas GRK2 and SSTR subtype 2 were significantly higher (P < .05). Likewise, β-arrestin 1 levels were inversely correlated with the in vivo response to acute octreotide test (P = .001), whereas GRK2 and SSTR subtype 2 expression were positively correlated (P < .05). In conclusion, for the first time, we characterized GRK2, β-arrestin 1, and β-arrestin 2 expression in a representative number of pituitary adenomas. β-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment.

  13. 核苷(酸)类似物治疗慢性乙型肝炎部分应答后加用α干扰素继续治疗疗效分析%Serological response of interferon-alpha-1b boasting regimen after virological response to nucleoside analogue treatment in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    林琪; 余雪平; 苏智军; 郭如意

    2013-01-01

    Objective To evaluate the serological response of interferon-alpha-1b (INF-α-1b)boasting regimen after virological response to nucleoside analogue treatment in patients with chronic hepatitis B (CHB).Methods 71 patients with HBeAg-positive CHB were selected,and they had had HBV DNA loss and alanine aminotransferase (ALT)normalization,but had had not HBeAg negativity to nucleoside analogue treatment.Thirtyeight patients were treated with nucleoside analogues they always received and INF-α-lb,while 33 patients continued nucleoside analogues for 48 weeks.Results At the end of 36 weeks of treatment,the negative rate of serum HBeAg in combination group was significantly higher than that in nucleoside group (36.8% vs.15.2%,P=0.039);At 48 weeks,the negative rate of serum HBeAg (42.1%)and HBeAg/anti-HBe seroconversion rate (36.8%) were significantly higher in the former group than those (18.2% and 15.2%,respectively,P=0.030 and 0.039) in the latter;There were no ALT and HBV DNA fluctuation and obvious adverse reactions in the two groups.Conclusion IFN-α might rescue the nucleoside analogues therapy to improve HBeAg/anti-HBe seroconversion rate.%目的 比较核苷(酸)类似物(NA)治疗慢性乙型肝炎(CHB)部分应答后加用α-干扰素组与未加用干扰素组的疗效.方法 筛选出71例经NA抗病毒治疗后出现HBV DNA转阴,ALT复常半年以上,但持续未出现HBeAg血清转换的HBeAg阳性CHB患者,随机分为联合干扰素组(n=38例)和单用NA组(n=33例),观察治疗4、12、24、36和48周两组患者HBeAg阴转率、HBeAg血清转换率、生化及HBV DNA水平的变化.结果 在治疗36周时,联合组HBeAg阴转率为36.8%,高于单用NA组的15.2%(P=0.039);在治疗48周时,联合组HBeAg阴转率和HBeAg血清转换率分别为42.1%和36.8%,明显高于单用NA组的18.2%和15.2%(P=0.030和0.039);治疗过程中两组均未出现ALT、HBV DNA波动及明显的不良反应.结论 干扰素可辅助NA治疗,

  14. 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

  15. Analogue Wormholes and Black Hole LASER Effect in Hydrodynamics

    CERN Document Server

    Peloquin, Cédric; Philbin, Thomas; Rousseaux, Germain

    2015-01-01

    We numerically study water wave packets on a spatially varying counter-current in the presence of surface tension. Depending on the details of the velocity profile, we show that traversable and bi-directional analogue wormholes exist in fluid mechanics. The limitations on traversability of wormholes in general relativity are absent here because of the dispersion of water waves and the ability to form flow profiles that are not solutions of Einstein's equations. We observe that negative energy can be trapped between analogue horizons forming a LASER-like cavity. Six horizons are involved in the trapping cavity because of the existence of two dispersive scales, in contrast to previous treatments which considered two horizons and one dispersive scale.

  16. Antimicrobial Photodynamic Therapy: Study of Bacterial Recovery Viability and Potential Development of Resistance after Treatment

    Science.gov (United States)

    Tavares, Anabela; Carvalho, Carla M. B.; Faustino, Maria A.; Neves, Maria G. P. M. S.; Tomé, João P. C.; Tomé, Augusto C.; Cavaleiro, José A. S.; Cunha, Ângela; Gomes, Newton C. M.; Alves, Eliana; Almeida, Adelaide

    2010-01-01

    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. PMID:20161973

  17. Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib

    Directory of Open Access Journals (Sweden)

    Reck M

    2015-07-01

    Full Text Available Martin Reck,1 Anders Mellemgaard2 1Department of Thoracic Oncology, Lung Clinic Grosshansdorf, and member of the Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 2Department of Oncology, Herlev University Hospital, Copenhagen, Denmark Abstract: There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy. Keywords: nintedanib, non-small cell lung cancer, second-line treatment, docetaxel, adenocarcinoma, antiangiogenesis

  18. 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. PMID:27119007

  19. Therapeutic Potential of Gramicidin S in the Treatment of Root Canal Infections.

    Science.gov (United States)

    Berditsch, Marina; Lux, Hannah; Babii, Oleg; Afonin, Sergii; Ulrich, Anne S

    2016-01-01

    An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix(®) paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20-40 min at a concentration of 40-80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100-200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication. PMID:27618065

  20. New approaches and potential treatments for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Francisco Max Damico

    2012-02-01

    Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  1. 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. PMID:26952432

  2. Lubricin: a novel potential biotherapeutic approaches for the treatment of osteoarthritis.

    Science.gov (United States)

    Bao, Jia-Peng; Chen, Wei-Ping; Wu, Li-Dong

    2011-06-01

    Osteoarthritis (OA) is a multi-factor disorder of sinovial joints, which characterized by escalated degeneration and loss of articular cartilage. Treatment of OA is a critical unmet need in medicine for regeneration of damaged articular cartilage in elderly. On the other hand, lubricin, a glycoprotein specifically synthesized by chondrocytes located at the surface of articular cartilage, has been shown to provide boundary lubrication of congruent articular surfaces under conditions of high contact pressure and near zero sliding speed. Lubrication of these surfaces is critical to normal joint function, while different gene expressions of lubricin had been found in the synovium of rheumatoid arthritis (RA) and OA. Moreover, mutations or lacking of lubricin gene have been shown to link to the joint disease such as camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), synovial hyperplasia and failure of joint function, suggesting an important role of lubricin in the pathogenesis of these joint disease. Recent studies demonstrate that administration with recombinant lubricin in the joint cavity would be effective in the prevention of cartilage degeneration in animal OA models. Therefore, a treatment with lubricin which would protect cartilage in vivo would be desirable. This article reviews recent findings with regard to the possible role of lubricin in the progression of OA, and further discusses lubricin as a novel potential biotherapeutic approaches for the treatment of OA.

  3. 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.

  4. Therapeutic Potential of Gramicidin S in the Treatment of Root Canal Infections

    Directory of Open Access Journals (Sweden)

    Marina Berditsch

    2016-09-01

    Full Text Available An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix® paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20–40 min at a concentration of 40–80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100–200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication.

  5. Therapeutic Potential of Gramicidin S in the Treatment of Root Canal Infections

    Science.gov (United States)

    Berditsch, Marina; Lux, Hannah; Babii, Oleg; Afonin, Sergii; Ulrich, Anne S.

    2016-01-01

    An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix® paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20–40 min at a concentration of 40–80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100–200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication. PMID:27618065

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

    Directory of Open Access Journals (Sweden)

    Laila Zafar

    2012-10-01

    Full Text Available 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 Sewage Treatment Plant (STP as organic fertilizer. For this purpose, chemical analysis of the waste water was carried out to determine the quality of raw waste water (influent and treated waste water (effluent intermittently. Furthermore, post-wastewater treatment, sewage sludge was analyzed for its chemical characteristics, i.e., for Total Nitrogen (TN, Total Phosphorous (TP and Organic Matter (OM contents; and microbial analyses for the presence of Total Coliforms, Fecal Coliforms and E. Coli was also carried out sewage sludge was exposed to sunlight for 0, 3 and 6 months. The results were with commercial compost (control similar characteristics. According to the results, pH, EC, TSS, COD and BOD5 were found very high in the influent however, after the waste water treatment; the effluent quality was found within the limits of National Environmental Quality standards (NEQs. On the other hand, TN, TP and OM content remained high in sewage sludge as compared to the controls. In order to enumerate harmful microbes in sewage sludge, microbial analyses for Total Coliforms, Fecal Coliforms and E. coli was carried out in pre-treated, UV-post-treated and control sludge samples. According to the results, the Total and Fecal Coliforms were found very high (>16000 MPN/g whereas, E. Coli population remained between (7000-12000 MPN/g. The most important aspect noted in this study was: as the sludge aged, this figure (7,000, 12,000, and 1,600 MPN/g after 0, 3 and 6 months

  7. 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

  8. 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

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:26915609

  9. Hydroperiod and hydraulic loading for treatment potential in urban tidal wetlands

    Directory of Open Access Journals (Sweden)

    T. T. Eaton

    2009-01-01

    Full Text Available Conventional methods of estimating water quality improvement due to wetland treatment are not well suited to the dynamic water level and wetted area fluctuations observed in coastal settings. We present a new method to quantify hydroperiod and hydraulic loading at different elevations in a coastal wetland profile in which the principal inflows and outflows are due to tides. We apply our method to an urban coastal setting (part of the New York-New Jersey Harbor Estuary where a major water quality problem persists due to fecal coliform contamination from combined sewer overflow (CSO discharges. Based on three types of simplified hydrograph, we show how such an approach and conceptual model of a terraced tidal wetland with constant mean slope can be used to assess hydrologic constraints for wetland vegetation species and the potential treatment effectiveness for adjacent impaired coastal waters. Resulting hydroperiods and hydraulic loading values decrease approximately exponentially with elevation along the wetland profile with considerable variation in overall slope depending on the hydrograph pattern. Application of a first-order contamination reduction model using our calculated hydraulic loadings indicates that such tidal treatment wetlands could reduce average fecal coliform concentrations in the range of 27% to 94% depending on the pattern of water level fluctuation, wetland surface elevation and vegetation density. Our analysis shows the performance potential for tidal wetlands to treat adjacent coastal waters. Restoration of existing salt marshes, and construction of new tidal wetlands would therefore be a promising part of an ecohydrologic strategy to improve water quality in contaminated urban coastal settings like the New York-New Jersey Harbor Estuary.

  10. Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Chan NC

    2015-06-01

    Full Text Available Noel C Chan,1,2 Vinai Bhagirath,1,3 John W Eikelboom1,3,41Population Health Research Institute, Hamilton, ON, Canada; 2Department of Haematology, Monash Medical Center, Clayton, VIC, Australia; 3Thrombosis and Atherosclerosis Research Institute, 4Department of Medicine, McMaster University, Hamilton, ON, CanadaAbstract: Venous thromboembolism (VTE, which includes deep vein thrombosis and pulmonary embolism, is a common and potentially preventable cause of morbidity and mortality. Unfractionated heparin, low-molecular-weight heparin, and warfarin have been the cornerstone of VTE prevention and treatment but are being replaced by recently approved non-vitamin K antagonist oral anticoagulants (NOACs: dabigatran, rivaroxaban, apixaban, and edoxaban. The NOACs are at least as effective and as safe as heparins and warfarin for VTE prevention and treatment and are more convenient because they have a low propensity for food and drug interactions and are given in fixed doses without routine coagulation monitoring. The remaining limitations of currently available NOACs include their dependence on renal and hepatic function for clearance, and the lack of an approved antidote. Betrixaban is a new NOAC with distinct pharmacological characteristics: minimal renal clearance, minimal hepatic metabolism, and long half-life. It has undergone successful Phase II studies in orthopedic thromboprophylaxis, and in stroke prevention in atrial fibrillation. Currently, it is being evaluated in a Phase III trial of extended thromboprophylaxis in medical patients (APEX study. In this article, we describe the development of betrixaban, review its pharmacological profile, discuss the results of clinical trials, and examine its potential for VTE prevention and treatment.Keywords: betrixaban, factor Xa inhibitors, anticoagulant, pharmacology, venous thromboembolism

  11. Evaluation of antioxidant potential of mango after formalin treatment during preservation

    Directory of Open Access Journals (Sweden)

    G.M. Masud Parvez

    2016-06-01

    Full Text Available Free radicals are producing continuously inside the living cell as a part of normal metabolic process and responsible for the generation of various types of disease such as cancer, cardiovascular disease, neurological disease, pulmonary disease, rheumatoid arthritis, nephropathy, ocular disease etc. Antioxidants are continuously counterbalancing the oxidative radical by breakdown or neutralizing the free radical. Various fruits and plant parts possesses antioxidant activity for example our studied sample mango has antioxidant property but when it treated with formalin it markedly reduces antioxidant potential of it. In phosphomolybdate assay it is found that normal mango peel contains more antioxidant activity than mango flesh, but treatment with formalin, antioxidant potential decreases in both peels and fleshes. Similar result was found in iron reducing power assay and DPPH radical scavenging assay where it is found that normal mango peel has almost similar scavenging property as compared to standard BHT. Normal mango peel (NP exhibits very high radical scavenging activity (IC50 is 4.2. At 100 μg/ml radical scavenging activity of normal mango peel (NP is 93.79%, but formalin treated mango peel (FP at same concentration possess scavenging property 76.36%, where as standard antioxidant scavenges about 93.95%. Scavenging power of normal mango flesh (NF is 39.57% and in formalin treated mango flesh (FF scavenging potential is only 7.12% at 100 μg/ml.

  12. 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. PMID:26810030

  13. Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions.

    Science.gov (United States)

    Sherrill, Joel T

    2016-01-01

    This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing. PMID:27347782

  14. The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds.

    Directory of Open Access Journals (Sweden)

    Allen J Duplantier

    2013-07-01

    Full Text Available Diabetic patients often have ulcers on their lower-limbs that are infected by multiple biofilm-forming genera of bacteria, and the elimination of the biofilm has proven highly successful in resolving such wounds in patients. To that end, antimicrobial peptides have shown potential as a new anti-biofilm approach. The single human cathelicidin peptide LL-37 has been shown to have antimicrobial and antibiofilm activity against multiple gram-positive and gram-negative human pathogens, and have wound-healing effects on the host. The combination of the anti-biofilm effect and wound-healing properties of LL-37 may make it highly effective in resolving polymicrobially infected wounds when topically applied. Such a peptide or its derivatives could be a platform from which to develop new therapeutic strategies to treat biofilm-mediated infections of wounds. This review summarizes known mechanisms that regulate the endogenous levels of LL-37 and discusses the antibiofilm, antibacterial and immunological effects of deficient versus excessive concentrations of LL-37 within the wound environment. Here, we review recent advances in understanding the therapeutic potential of this peptide and other clinically advanced peptides as a potential topical treatment for polymicrobial infected wounds.

  15. Betaine: a potential agent for the treatment of hepatopathy associated with short bowel syndrome

    Directory of Open Access Journals (Sweden)

    Guilherme Teixeira Araújo

    2014-06-01

    Full Text Available Background: The hepatopathy associated with short bowel syndrome (SBS is a multifactorial disease associated with poor prognosis. Besides intestinal transplantation, no other treatment has been shown effective. The current study evaluated the efficacy of betaine for the treatment of hepatopathy associated with SBS. Methods: A prospective, unicentric, non-placebo controlled trial was carried out. After initial evaluation, 10g of betaine anhydrous was administrated to SBS patients in two divided doses for three months. The hepatic steatosis was assessed through nuclear magnetic resonance (NMR, the inflammatory response by interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α and ferritin, besides the hepatic lesion through hepatic enzymes and bilirubin. Furthermore, the effect of betaine on homocysteine was evaluated as well as its safety and tolerability in this group of patients. Results: After three months supplementation, patients showed decreased percentage of hepatic fat (p = 0.03 through triphasic NMR examination. There was no significant reduction of serum levels for inflammatory proteins and hepatic lesion markers. Homocysteinemia also did not present significant decrease. The most prevalent side effects were diarrhea and nausea, reported in 62% of the participants; however, these symptoms were transient and not severe enough to justify the treatment interruption. Parenteral nutrition-dependent patients did not present different hepatic lesion degree compared to patients who do not need the prolonged use of it. Conclusions: Betaine was shown to be a potential agent for the treatment of hepatopathy associated with SBS, which was evidenced by NMR, although the markers for hepatic lesion have not presented significant decrease.

  16. 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.

  17. Geoscience in Support of a Mars Methane Analogue Mission

    Science.gov (United States)

    Boivin, Alexandre

    The Mars Methane Analogue Mission, funded by the Canadian Space Agency through its Analogue Missions program, simulates a Mars rover mission whose purpose is to detect, analyse, and determine the source of methane emissions on the planet's surface. As part of this project, both an electromagnetic induction sounder (EMIS) and a high-resolution triangulation-based 3D laser scanner were tested in the field to demonstrate the benefit of including these instruments on future rover missions. EMIS data was inverted in order to derive information on the conductivity and magnetic susceptibility of the near subsurface. 3D laser scanner data was processed with fracture detection as a goal in order to simplify the search for areas of potential methane seepage. Both instruments were found to be very valuable for future rover missions of this type.

  18. Are structural analogues to bisphenol A a safe alternative?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Gitte Alsing;

    2013-01-01

    Bisphenol A (BPA) is often used in polycarbonate plastics, coatings of food and drink cans, and in thermal papers. Foods are thought to be a major human exposure route and human biomonitoring data suggest widespread exposure. BPA is suspected of contributing to effects such as increased birth...... weight, behavioral changes in children, cardiovascular disease, and diabetes. Regulatory initiatives and increased public awareness, related to the potential adverse effects of BPA, has led to an incitement to find alternative compounds. Structural analogues of BPA are available on the market, some...... of which are found in foods and have been measured in humans. Due to the structural analogy there is an inherent risk that these compounds may lead to similar effects as BPA. The aim of this study was to characterize the toxicological profile of BPA and the five analogues using in vitro assays assessing...

  19. Alligator Rivers Analogue Project an OECD/NEA international project

    International Nuclear Information System (INIS)

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as natural analogue of the far field behaviour of high level waste repository following groundwater ingress. A number of mathematical modelling approaches were developed for processes as divers as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained. 6 refs., 1 tab., 1 fig

  20. Alligator rivers analogue project an OECD/NEA international project

    International Nuclear Information System (INIS)

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as a natural analogue of the far field behaviour of high level waste repositories following groundwater ingress. A number of mathematical modelling approaches were developed for processes as diverse as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained

  1. Synthesis and biological evaluation of febrifugine analogues.

    Science.gov (United States)

    Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

    2014-12-01

    A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity. PMID:25632466

  2. Cross-linked polymeric nanogel formulations of 5'-triphosphates of nucleoside analogues: role of the cellular membrane in drug release.

    Science.gov (United States)

    Vinogradov, Serguei V; Kohli, Ekta; Zeman, Arin D

    2005-01-01

    Activation of cytotoxic nucleoside analogues in vivo depends primarily on their cell-specific phosphorylation. Anticancer chemotherapy using nucleoside analogues may be significantly enhanced by intracellular administration of active phosphorylated drugs. However, the cellular transport of anionic compounds is very ineffective and restricted by many drug efflux transporters. Recently developed cationic nanogel carriers can encapsulate large amounts of nucleoside 5'-triphosphates that form polyionic complexes with protonated amino groups on the polyethylenimine backbone of the nanogels. In this paper, the 5'-triphosphate of an antiviral nucleoside analogue, 3'-azido-2',3'-dideoxythymidine (AZT), was efficiently synthesized and its complexes with nanogels were obtained and evaluated as potential cytotoxic drug formulations for treatment of human breast carcinoma cells. A selective phosphorylating reagent, tris-imidazolylphosphate, was used to convert AZT into the nucleoside analogue 5'-triphosphate using a one-pot procedure. The corresponding 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP) was isolated with high yield (75%). Nanogels encapsulated up to 30% of AZTTP by weight by mixing solutions of the carrier and the drug. The AZTTP/nanogel formulation showed enhanced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB-231, demonstrating IC50 values 130-200 times lower than those values for AZT alone. The exact mechanism of drug release from nanogels remains unclear. One mechanism could involve interaction with negatively charged counterions. A high affinity of nanogels to isolated cellular membranes has been observed, especially for nanogels made of amphiphilic block copolymer, Pluronic P85. Cellular trafficking of nanogel particles, contrasted by polyethylenimine-coordinated copper(II) ions, was studied by transmission electron microscopy (TEM), which revealed membranotropic properties of nanogels. A substantial release of encapsulated drug was

  3. 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

  4. Space analogue studies in Antarctica

    Science.gov (United States)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  5. 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

  6. 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.

  7. 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...

  8. {sup 90}Y-oxine-ethiodol, a potential radiopharmaceutical for the treatment of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu Junfeng; Haefeli, U.O. E-mail: hafeliu@ccf.org; Sands, Mark; Dong Yonghua

    2003-05-01

    Ethiodol (or lipiodol) is selectively retained in hepatocellular carcinoma and is used as a vehicle to deliver radioactive agents following intraarterial hepatic infusion. We prepared the lipophilic complex {sup 90}Y-oxine with a radiolabeling efficiency of 97.6{+-}1.1%. After extraction into ethiodol, a stability test in serum at 37 deg. C showed that 87.8% of the {sup 90}Y remained ethiodol-bound for 7 days. Bremsstrahlung imaging of a rabbit for 48 h confirmed that the homogeneous mixture of radiolabeled {sup 90}Y-oxine and ethiodol stayed in the targeted liver lobe. This radiopharmaceutical is thus a potential candidate for the treatment of non-resectable liver cancer.

  9. 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

  10. Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

    International Nuclear Information System (INIS)

    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

  11. 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

  12. The Greenland Analogue Project. Yearly Report 2009

    International Nuclear Information System (INIS)

    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

  13. 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

  14. Effects of Electric Potential Treatment of a Chromium Hexacyanoferrate Modified Biosensor Based on PQQ-Dependent Glucose Dehydrogenase

    OpenAIRE

    Ta-Feng Tseng; Yang-Li Yang; Yuh-Jiuan Lin; Shyh-Liang Lou

    2010-01-01

    A novel potential treatment technique applied to a glucose biosensor that is based on pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (GDH) and chromium hexacyanoferrate (CrHCF) incorporated into a platinum (Pt) electrode was demonstrated. CrHCF, serving as a mediator, was electrochemically deposited on the Pt electrode as ascertained by CV, SEM, FTIR and XPS measurements. The potential treatment of CrHCF, which converts Fe(II) to Fe(III), enables the glucose detection. The amp...

  15. Profile of pacritinib and its potential in the treatment of hematologic disorders

    Directory of Open Access Journals (Sweden)

    Hatzimichael E

    2014-08-01

    Full Text Available Eleftheria Hatzimichael, Evangelos Tsolas, Evangelos Briasoulis Department of Haematology, University Hospital of Ioannina, Ioannina, Greece Abstract: Pacritinib (previously known as SB-1518 is an innovative selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3 providing potential in the treatment of hematological malignancies such as myeloproliferative neoplasias, acute myeloid leukemia, and various lymphomas. Pacritinib has potent antiproliferative activity in Janus kinase 2 and/or FMS-related tyrosine kinase 3 activity-dependent cell lines and an ability to promote apoptosis and inhibit the signal transducers and activators of transcription (STAT pathway. Pharmacokinetic studies have indicated a good per os bioavailability and favorable kinetic parameters. To date, promising results have been produced in five completed early-phase clinical trials in which pacritinib has been studied. Pacritinib displayed interesting activity and an acceptable safety profile, with mild to moderate gastrointestinal disorders being its most common adverse effects. Keywords: pacritinib, SB-1518, JAK inhibitors, myeloproliferative neoplasms, acute myeloid leukemia, lymphoma, treatment

  16. Potential of combined fungal and bacterial treatment for color removal in textile wastewater.

    Science.gov (United States)

    Novotný, Ceněk; Svobodová, Kateřina; Benada, Oldřich; Kofroňová, Olga; Heissenberger, Andreas; Fuchs, Werner

    2011-01-01

    Low efficiency of dye removal by mixed bacterial communities and high rates of dye decolorization by white-rot fungi suggest a combination of both processes to be an option of treatment of textile wastewaters containing dyes and high concentrations of organics. Bacteria were able to remove mono-azo dye but not other chemically different dyes whereas decolorization rates using Irpex lacteus mostly exceeded 90% within less than one week irrespective of dye structure. Decolorization rates for industrial textile wastewaters containing 2-3 different dyes by fungal trickling filters (FTF) attained 91%, 86%, 35% within 5-12 d. Sequential two-step application of FTF and bacterial reactors resulted in efficient decolorization in 1st step (various single dyes, 94-99% within 5 d; wastewater I, 90% within 7 d) and TOC reduction of 95-97% in the two steps. Large potential of combined use of white-rot fungi and traditional bacterial treatment systems for bioremediation of textile wastewaters was demonstrated.

  17. Potentially pathogenic free-living amoebae (FLA) isolated in Spanish wastewater treatment plants.

    Science.gov (United States)

    García, A; Goñi, P; Clavel, A; Lobez, S; Fernandez, M T; Ormad, M P

    2011-10-01

    This work studies the characterization of pathogenic free-living amoebae (FLA) from sewage effluents. Some of them, such as Acanthamoeba, Naegleria, Hartmannella, Sappinia, Balamuthia and Paravahlkampfia have been reported as a cause of diseases in humans. Therefore, the study of their habitats and their pathogenicity has become necessary. The population of potentially pathogenic FLA was analysed in five Spanish wastewater treatment plants. Five of the seven FLA isolated were identified as genus Acanthamoeba genotypes T3, T4, T7 and T9. Hartmannella and Naegleria were also isolated. Acanthamoeba demonstrated great thermotolerance and osmotolerance. It was also observed that treatment with sodium hypochlorite showed no significative reduction in the number of amoeba at concentrations of 0-100 ppm. The high resistance of FLA cysts to disinfection methods is a trojan horse for public health insofar as they colonize water systems and allow the survival of intracellular microorganisms resistant to FLA. The results of this work advance current knowledge of the FLA population.

  18. Impacts of inoculum pre-treatments on enzyme activity and biochemical methane potential.

    Science.gov (United States)

    Wang, Bing; Strömberg, Sten; Nges, Ivo Achu; Nistor, Mihaela; Liu, Jing

    2016-05-01

    Biochemical methane potential (BMP) tests were carried out to investigate the influence of inoculum pre-treatments (filtration and pre-incubation) on methane production from cellulose and wheat straw. First-order model and Monod model were used to evaluate the kinetic constants of the BMP assays. The results demonstrated that fresh inoculum was the best option to perform BMP tests. This was evidenced by highest enzyme activity (0.11 U/mL) and highest methane yields for cellulose (356 NmL CH4/gVS) as well as wheat straw (261 NmL CH4/gVS). Besides, high biodegradability (85.8% for cellulose and 61.3% for wheat straw) was also obtained when the fresh inoculum was used. Moreover, a kinetic evaluation showed that inoculum pre-incubation at 37°C or storage at 4°C introduced a lag-time whereas the effects on hydrolysis rate were less consequent. In summary, pre-treatments affected the enzyme activity of the inoculum, and further on, significantly influenced the methane production and the degradation kinetics of the investigated substrates. It is recommended that filtration of inoculum should be avoided unless in case too large particles therein. PMID:26526543

  19. Therapeutic Potential of Retinoid X Receptor Modulators for the Treatment of the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Jane A. Pinaire

    2007-01-01

    Full Text Available The increasing prevalence of obesity is a fundamental contributor to the growing prevalence of the metabolic syndrome. Rexinoids, a class of compounds that selectively bind and activate RXR, are being studied as a potential option for the treatment of metabolic syndrome. These compounds have glucose-lowering, insulin-sensitizing, and antiobesity effects in animal models of insulin resistance and type 2 diabetes. However, undesirable side effects such as hypertriglyceridemia and suppression of the thyroid hormone axis also occur. This review examines and compares the effects of four RXR-selective ligands: LGD1069, LG100268, AGN194204, and LG101506, a selective RXR modulator. Similar to selective modulators of other nuclear receptors such as the estrogen receptor (SERMs, LG101506 binding to RXR selectively maintains the desirable characteristic effects of rexinoids while minimizing the undesirable effects. These recent findings suggest that, with continued research efforts, RXR-specific ligands with improved pharmacological profiles may eventually be available as additional treatment options for the current epidemic of obesity, insulin resistance, type 2 diabetes, and all of the associated metabolic sequelae.

  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. PMID:26004052

  1. Sludge-Drying Lagoons: a Potential Significant Methane Source in Wastewater Treatment Plants.

    Science.gov (United States)

    Pan, Yuting; Ye, Liu; van den Akker, Ben; Ganigué Pagès, Ramon; Musenze, Ronald S; Yuan, Zhiguo

    2016-02-01

    "Sludge-drying lagoons" are a preferred sludge treatment and drying method in tropical and subtropical areas due to the low construction and operational costs. However, this method may be a potential significant source of methane (CH4) because some of the organic matter would be microbially metabolized under anaerobic conditions in the lagoon. The quantification of CH4 emissions from lagoons is difficult due to the expected temporal and spatial variations over a lagoon maturing cycle of several years. Sporadic ebullition of CH4, which cannot be easily quantified by conventional methods such as floating hoods, is also expected. In this study, a novel method based on mass balances was developed to estimate the CH4 emissions and was applied to a full-scale sludge-drying lagoon over a three year operational cycle. The results revealed that processes in a sludge-drying lagoon would emit 6.5 kg CO2-e per megaliter of treated sewage. This would represent a quarter to two-thirds of the overall greenhouse gas (GHG) emissions from wastewater-treatment plants (WWTPs). This work highlights the fact that sludge-drying lagoons are a significant source of CH4 that adds substantially to the overall GHG footprint of WWTPs despite being recognized as a cheap and energy-efficient means of drying sludge. PMID:26642353

  2. Therapeutic potential of Gastrodia elata Blume for the treatment of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Guang-Biao Huang; Soo-Hyun Park; Eun-Ock Park; Eun-Kyung Choi; Young-Chul Chung; Tong Zhao; Sushma Shrestha Muna; Hong-Mei Jin; Jong-Il Park; Kyu-Sik Jo; Bo-Hee Lee; Soo-Wan Chae; Sun-Young Kim

    2013-01-01

    Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide (Aβ)-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer's disease, we established a rat model of Alzheimer's disease by injecting Aβ25 35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer's disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while Ellman method showed significant decrease in the activity of acetylcholinesterase in all three regions (prefrontal cortex, medial septum and hippocampus). These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer's disease.

  3. Demethylation of FANCF gene may be a potential treatment through inhibiting the proliferation of cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Min Li; Chanyu Zhang

    2013-01-01

    Objective: The aim of the study was to explore the effect of demethylating agent 5-Aza-2'-deoxycytidine (5-ADC) on expression of Fanconi anemia complementation group F (FANCF) gene and the proliferation of cervical cancer cells, to observe cell's sensitivity to chemotherapeutic drug taxol, and to explore the antitumor effect of 5-ADC as well as the new treatment of cervical cancer. Methods: Cervical cancer cell lines SiHa (FANCF gene full-methylated) and Hela (unmethylated) were treated with 5-ADC. We used the methylation-specific PCR (MSP), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot to detect the FANCF methylation, mRNA and protein respectively. The 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of cells. The cytotoxicity of taxol was measured by flow cytometer. The nude mice bearing SiHa was used to observe the effect of 5-ADC in vivo. Results: Inhibition of DNA promoter methylation by 5-ADC reactivated the expression of FANCF mRNA and protein in SiHa cells, consistent with decreased growth speed and increased taxol resistance. These results were proven in experiments in vivo. Conclusion: The 5-ADC probably become a potential treatment drug through inhibiting the proliferation of cervical cancer cells in taxol-resistant patients.

  4. Sulfur analogues of psychotomimetic agents. Monothio analogues of mescaline and isomescaline.

    Science.gov (United States)

    Jacob, P; Shulgin, A T

    1981-11-01

    Two monothio analogues of mescaline and three monothio analogues of 2,3,4-trimethoxyphenethylamine (isomescaline) have been synthesized and characterized. Only the two mescaline analogues (3-and 4-thiomescaline) were found to be psychotomimetics in man, being 6 and 12 times more potent than mescaline, respectively. All five compounds can serve as substrates for bovine plasma monoamine oxidase in vitro, but no positive correlation is apparent between the extent of enzymatic degradation and human psychotomimetic potency.

  5. Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety.

    Science.gov (United States)

    Litten, Raye Z; Wilford, Bonnie B; Falk, Daniel E; Ryan, Megan L; Fertig, Joanne B

    2016-01-01

    Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM-5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed-some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds. PMID:26928397

  6. The Potential Therapeutic Effect of Green Tea in Treatment of Vernal Keratoconjunctivitis

    Directory of Open Access Journals (Sweden)

    Mahnaz Mosallaei

    2008-05-01

    Full Text Available Vernal keratoconjunctivitis is a chronic, recurrent and severe ocular allergic disease, which is characterized by persistent allergic inflammation of the conjunctiva. It can be accompanied by ocular discomfort and visual disturbance. All forms are characterized by intense itching, tearing, mucous secretions and a severe photophobia, which often forces children to live virtually in dark places. Conjunctival proliferative changes, such as the formation of giant papillae are the characteristic findings of affected individuals. Giant papillae develop as a result of infiltration of inflammatory cells, changes in the epithelial layer, and increased deposition of extracellular matrix molecules such as collagen and proliferation of conjunctival fibroblasts. Currently several therapeutic options such as corticosteroids, mast cell stabilizers and cyclosporine are applied for treatment of Vernal keratoconjunctivitis but in long-term, the chronic and recurrent nature of this problem leads to failure or appearance of side effects of current treatment in many patients. Recently, Green tea extract and its principal active ingredient, epigallocatechin gallate , are gaining attention and increased usage due to its healthful properties. It has considerable anticatactogenic effect by inducing apoptosis in lens epithelial cells and antioxidant effects. Also its great benefits were achieved in attenuation of damaging influences to the retina caused by ischemia/reperfusion. Based on evidences supported beneficial effects of green tea, we hypothesize that local administration of green tea and its extract seems to be a proper substitute or adjunct to current treatments of Vernal keratoconjunctivitis. This plant contains a series of antioxidants that can abolish the process of allergic cascade. Moreover, by suppressing TNF-alpha potentially, it can reduce proinflammatory reaction, as well as fibroblast proliferation and subsequently decrease giant papilla formation

  7. 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. PMID:25917290

  8. Acoustojet: acoustic analogue of photonic jet phenomenon

    CERN Document Server

    Minin, Igor V

    2016-01-01

    It has been demonstrated for the first time that an existence of acoustic analogue of photonic jet phenomenon, called acoustojet, providing for subwavelength localization of acoustic field in the shadow area of arbitrary 3D penetrable mesoscale particle, is possible.

  9. Total Synthesis of the Analogue of Icogenin

    Institute of Scientific and Technical Information of China (English)

    Shu Jie HOU; Peng XU; Liang ZHOU; De Quan YU; Ping Sheng LEI; Chuan Chun ZOU

    2006-01-01

    One of the analogues of icogenin, a natural furostanol saponin showing strong cytotoxic effect on cancer cell, was first synthesized via convergent strategy by using diosgenin and available monosaccharides as starting materials,

  10. Second-Generation Fluorescent Quadracyclic Adenine Analogues

    DEFF Research Database (Denmark)

    Dumat, Blaise; Bood, Mattias; Wranne, Moa S.;

    2015-01-01

    Fluorescent base analogues comprise a group of increasingly important molecules for the investigation of nucleic acid structure, dynamics, and interactions with other molecules. Herein, we report on the quantum chemical calculation aided design, synthesis, and characterization of four new putativ...

  11. Voltammetric and Theoretical Study of the Redox Properties of Rubrolide Analogues

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • The redox properties of rubrolide analogues were investigated by cyclic voltammetry. • A computational method to predict the redox potential of rubrolides was developed. • Prediction of Epc of rubrolides analogues was made by DTF calculations. • Rubrolide Epc correlates to the ability to inhibit the photosynthetic electron flow. - Abstract: To understand and predict the relationship between the redox potential and the inhibitory effect of rubrolide analogues upon the photosynthetic electron transport chain, their redox properties were studied. The reduction potential was determined experimentally in DMSO by means of cyclic voltammetry, and theoretically by using B3LYP/6-31G(d,p) and MPWB1 K/TZVP computational methods. A good correlation was obtained between the two datasets, MPWB1 K/TZVP being the best methodology (correlation coefficient of 0.965 and standard deviation of 0.034, against 0.932 and 0.047 for B3LYP/6-31G(d,p)). A significant relationship was observed between the redox potential of the rubrolide analogues and their ability to interfere with the Hill reaction: the higher the first reduction potential, the more effective the inhibitor. These results will allow for predicting the behavior of novel analogues as inhibitors of the Hill reaction, and directing the synthetic strategy towards more potent inhibitors targeting the photosynthetic electron transport

  12. K-111: the emerging evidence for its potential in the treatment of the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Margaret Duggan-Keen

    2006-03-01

    Full Text Available Margaret Duggan-KeenCore Medical Publishing, Knutsford, UKIntroduction: Prevalence of the metabolic syndrome has increased dramatically in recent years. Optimal patient care demands a multifaceted approach, with many individuals requiring several therapies to minimize the significant associated cardiovascular burden. The need for novel agents in the management of the metabolic syndrome is emphasized by the current lack of drugs to treat insulin resistance, one of the major components of the metabolic syndrome that has several deleterious consequences. Aims: The objective of this review is to assess the emerging evidence for the potential use of K-111 in treatment of the metabolic syndrome.Emerging evidence: K-111 is a peroxisome proliferator-activated receptor (PPAR-alfa agonist that, in preclinical studies, has shown efficacy in improving insulin resistance, reducing bodyweight, and ameliorating atherogenic dyslipidemia. Preliminary evidence suggests that toxicity and adverse events are low.Profile: The improvements in obesity and insulin resistance, together with other beneficial effects following activation of PPAR alfa by K-111 in preclinical models, are encouraging and offer several potential advantages over currently available therapies for patients with the metabolic syndrome. However, K-111 is at an early stage of development and establishment of its role will require full analysis of clinical trials carefully designed to determine its overall benefits in this increasingly important disease area.Key words: BM 17.0744, cardiovascular diseases, insulin resistance, K-111, metabolic syndrome X, PPAR alfa

  13. Novel NSAID-Derived Drugs for the Potential Treatment of Alzheimer’s Disease

    Science.gov (United States)

    Cacciatore, Ivana; Marinelli, Lisa; Fornasari, Erika; Cerasa, Laura S.; Eusepi, Piera; Türkez, Hasan; Pomilio, Cristina; Reale, Marcella; D’Angelo, Chiara; Costantini, Erica; Di Stefano, Antonio

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested for the potential treatment of neurodegenerative diseases, such as Alzheimer’s disease (AD). Prolonged use of NSAIDs, however, produces gastrointestinal (GI) toxicity. To overcome this serious limitation, the aim of this study was to develop novel NSAID-derived drug conjugates (Anti-inflammatory-Lipoyl derivatives, AL4–9) that preserve the beneficial effects of NSAIDS without causing GI problems. As such, we conjugated selected well-known NSAIDs, such as (S)-naproxen and (R)-flurbiprofen, with (R)-α-lipoic acid (LA) through alkylene diamine linkers. The selection of the antioxidant LA was based on the proposed role of oxidative stress in the development and/or progression of AD. Our exploratory studies revealed that AL7 containing the diaminoethylene linker between (R)-flurbiprofen and LA had the most favorable chemical and in vitro enzymatic stability profiles among the synthesized compounds. Upon pretreatment, this compound exhibited excellent antioxidant activity in phorbol 12-miristate 13-acetate (PMA)-stimulated U937 cells (lymphoblast lung from human) and Aβ(25–35)-treated THP-1 cells (leukemic monocytes). Furthermore, AL7 also modulated the expression of COX-2, IL-1β and TNF-α in these cell lines, suggesting anti-inflammatory activity. Taken together, AL7 has emerged as a potential lead worthy of further characterization and testing in suitable in vivo models of AD. PMID:27376271

  14. Novel NSAID-Derived Drugs for the Potential Treatment of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Ivana Cacciatore

    2016-06-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs have been suggested for the potential treatment of neurodegenerative diseases, such as Alzheimer’s disease (AD. Prolonged use of NSAIDs, however, produces gastrointestinal (GI toxicity. To overcome this serious limitation, the aim of this study was to develop novel NSAID-derived drug conjugates (Anti-inflammatory-Lipoyl derivatives, AL4–9 that preserve the beneficial effects of NSAIDS without causing GI problems. As such, we conjugated selected well-known NSAIDs, such as (S-naproxen and (R-flurbiprofen, with (R-α-lipoic acid (LA through alkylene diamine linkers. The selection of the antioxidant LA was based on the proposed role of oxidative stress in the development and/or progression of AD. Our exploratory studies revealed that AL7 containing the diaminoethylene linker between (R-flurbiprofen and LA had the most favorable chemical and in vitro enzymatic stability profiles among the synthesized compounds. Upon pretreatment, this compound exhibited excellent antioxidant activity in phorbol 12-miristate 13-acetate (PMA-stimulated U937 cells (lymphoblast lung from human and Aβ(25–35-treated THP-1 cells (leukemic monocytes. Furthermore, AL7 also modulated the expression of COX-2, IL-1β and TNF-α in these cell lines, suggesting anti-inflammatory activity. Taken together, AL7 has emerged as a potential lead worthy of further characterization and testing in suitable in vivo models of AD.

  15. Assessing the ecotoxicity of metal nano-oxides with potential for wastewater treatment.

    Science.gov (United States)

    Nogueira, V; Lopes, I; Rocha-Santos, T A P; Rasteiro, M G; Abrantes, N; Gonçalves, F; Soares, A M V M; Duarte, A C; Pereira, R

    2015-09-01

    The rapid development of nanotechnology and the increasing use of nanomaterials (NMs) raise concern about their fate and potential effects in the environment, especially for those that could be used for remediation purposes and that will be intentionally released to the environment. Despite the remarkable emerging literature addressing the biological effects of NMs to aquatic organisms, the existing information is still scarce and contradictory. Therefore, aimed at selecting NMs for the treatment of organic and inorganic effluents, we assessed the potential toxicity of NiO (100 and 10-20 nm), Fe2O3 (≈85 × 425 nm), and TiO2 (Lemna minor, Daphnia magna, Brachionus plicatilis, and Artemia salina. Also a mutagenic test was performed with two Salmonella typhimurium strains. Suspensions of each NM, prepared with the different test media, were characterized by dynamic light scattering (DLS) and eletrophoretic light scattering (ELS). For the assays with marine species, no toxicity was observed for all the compounds. In opposite, statistically significant effects were produced on all freshwater species, being D. magna the most sensitive organism. Based on the results of this study, the tested NMs can be classified in a decreasing order of toxicity NiO (100 nm) > NiO (10-20 nm) > TiO2 ( Fe2O3, allowing to infer that apparently Fe2O3 NMs seems to be the one with less risks for receiving aquatic systems. PMID:25940480

  16. The structure activity relationship of discodermolide analogues.

    Science.gov (United States)

    Shaw, Simon J

    2008-03-01

    The marine polyketide discodermolide is a member of a class of natural products that stabilize microtubules. Many analogues have been synthesized suggesting that few changes can be made to the internal carbon backbone. Both ends of the molecule, however, can be modified. The majority of analogues have been generated via modification of the lactone region. This suggests that significant simplifications can be made in this region provided that the lactone moiety is maintained.

  17. Newer insulin analogues and inhaled insulin

    OpenAIRE

    Girish C; Manikandan S; Jayanthi M

    2006-01-01

    Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid...

  18. Synthesis of caged Garcinia xanthone analogues

    OpenAIRE

    Cho, Woo Cheal

    2009-01-01

    A new synthetic strategy is developed toward the synthesis of the caged Garcinia xanthone analogues. The key to the strategy is a Pd-catalyzed reverse prenylation reaction. This new synthetic approach provides a rapid and efficient access to various caged analogues, including cluvenone which is known to induce apoptosis and exhibit significant cytotoxicity in various cancer cell lines. Evaluation of their growth inhibitory activities also leads to identification of the pharmacophoric motif of...

  19. Importance of food waste pre-treatment efficiency for global warming potential in life cycle assessment of anaerobic digestion systems

    DEFF Research Database (Denmark)

    Carlsson, My; Naroznova, Irina; Møller, Jacob;

    2015-01-01

    treatment of the refuse. The objective of this study was to investigate how FW pre-treatment efficiency impacts the environmental performance of waste management, with respect to global warming potential (GWP). The modeling tool EASETECH was used to perform consequential LCA focusing on the impact...

  20. Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections

    Directory of Open Access Journals (Sweden)

    Falci DR

    2013-10-01

    Full Text Available Diego R Falci,1,2 Alessandro C Pasqualotto2,31Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil; 2Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil; 3Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, BrazilAbstract: The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position

  1. Changes of evoked potentials and evaluation of mild hypothermia for treatment of severe brain injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To observe the changes of evoked pote ntials after severe brain injury and the effect of mild hypothermia on acute sev ere brain injury.   Methods: A total of 44 patients with severe closed head injury (GCS 3-8, admitted within 10 hours from injury) admitted from May 1998 to March 1999 were selected for this study. All patients were admitted into the intensiv e care unit and divided into 2 groups, Group A (GCS 3-5) and Group B (GCS 6 -8). Patients were also randomly assigned to either normothermia or hypothermia subgroups. Patients in the hypothermia group were cooled to 32-34℃. Median nerve short-latency somatosensory evoked potentials (SLSEP) and brain stem aud itory evoked potentials (BAEP) were recorded before cooling and 4, 24, 48, 72, 9 6 and 120 hours, respectively after cooling and temperature resuming. SLSEP and BAEP were measured at the same time in the normothermia group (control group). T he changes of evoked potentials (EP) were analyzed by statistical methods.   Results: In the Group B, N20 amplitudes in SLSEP and I/V amplitudes in BAEP after mild hypothermia treatment in the hypothermia group dif fered significantly from those in the control group (P<0.05). However, in the Group A, no significant difference in all paramet ers was found.   Conclusions: These results demonstrate that mild hypothermia tr eatment (32-34℃) in the Group B has a significant neuroelectrophysiological effect on severe brain injury. Nevertheless, the effect of mild hypothermia in t he Group A is not apparent and needs further studying.

  2. 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

  3. Potential of Constructed Wetland for Wastewater Treatment in Rural Areas in Kosovo

    Institute of Scientific and Technical Information of China (English)

    Lavdim Osmanaj[1; Agon Haxhikadrija[1; Pierre-Henri Dodane[2; Astrit Vokshi[3

    2015-01-01

    Republic of Kosovo has 1,304 settlements from which only 37 are urban and 1,267 are rural. Shown in percentage, only 39.2% (765,125) of inhabitants live in urban areas. The focus is to work and find the best and cheap solutions for the 60.8% (1,173,370) of inhabitants of the country which live in rural areas. From this number only 42% of them have access to the sewage network while 60.8% of them have implemented individual solutions (latrines) without any treatment, leading to a large pollution of the water bodies. The existing rural sewage networks are built only with septic tanks, poorly designed and do not fulfill the wastewater treatment criteria. Regarding this issue, the Kosovan legislation concerns only urban areas (settlements of more than 2,000 inhabitants) and is expected to be completed in 2014 for rural areas according to the EU (European Union) directive for wastewater discharge. As a pilot project, the CDI (community development initiatives) started with WWTP (waste water treatment plants) based on the Vertical Constructed Wetland option (french model) as it appears to be the most adapted option in this rolling, rural, and temperate climate context, implementing this kind of treatment in 3 villages for the first time in Kosovo. Through this, it is interesting to take a perspective on all the phases of these projects starting from feasibility reports, project design to concept and modalities of implementation and options for operation and maintenance, in order to assess how this technical option is feasible and replicable in the country at a large scale. It finally appears that the potential for constructed wetland in the Balkan region is promising as it provides a simple solution for most of the regional constraints, but requires skills to be developed locally for designing and building as well as a deeper consideration in the national regulation.

  4. 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

  5. A novel peptide sansalvamide analogue inhibits pancreatic cancer cell growth through G0/G1 cell-cycle arrest

    International Nuclear Information System (INIS)

    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

  6. Natural analogue studies as supplements to biomineralization research

    Energy Technology Data Exchange (ETDEWEB)

    McNeil, M.B. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    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{sub 4}SO{sub 4}(OH){sub 6{center_dot}}H{sub 2}O] and mineral morphologies unusual in corrosion [malachite, Cu{sub 2}CO{sub 3}(OH){sub 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].

  7. Synthetic analogues of natural semiochemicals as promising insect control agents

    International Nuclear Information System (INIS)

    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

  8. Ethyl Formate: A Potential Disinfestation Treatment for Eucalyptus Weevil (Gonipterus platensis) (Coleoptera: Curculionidae) in Apples.

    Science.gov (United States)

    Agarwal, Manjree; Ren, Yonglin; Newman, James; Learmonth, Stewart

    2015-12-01

    Export of Pink Lady apples from Australia has been significantly affected by infestations of adult eucalyptus weevils (Gonipterus platensis Marelli). These weevils cling tenaciously to the pedicel of apple fruit when selecting overwintering sites. As a result, apples infested with live G. platensis adults lead to rejection for export. Since the Montreal Protocol restricted use of methyl bromide as postharvest treatment, it was necessary to consider alternative safer fumigants for disinfestation of eucalyptus weevil. Laboratory experiments were conducted using concentrations of 5, 10, 15, 20, 25, 30, 40, and 80 mg/liter of ethyl formate. Complete control (100% mortality) was achieved at 25-30 mg/liter of ethyl formate at 22-24°C for 24-h exposure without apples. However, with 90-95% of the volume full of apples, complete control was achieved at 40 mg/liter of ethyl formate at 22-24°C for 24-h exposure. No phytotoxicity was observed and after one day aeration, residue of ethyl formate declined to natural levels (0.05-0.2 mg/kg). Five ethyl formate field trials were conducted in cool storages (capacity from 250-900 tons) and 100% kill of eucalyptus weevils were achieved at 50-55 mg/liter at 7-10°C for 24 h. Ethyl formate has great potential for preshipment treatment of apples. Its use is considerably cheaper and safer than already existing fumigants like methyl bromide and phosphine.

  9. Effects of symptomatic treatments on cutaneous hyperalgesia and laser evoked potentials during migraine attack.

    Science.gov (United States)

    de Tommaso, M; Losito, L; Libro, G; Guido, M; Di Fruscolo, O; Sardaro, M; Sciruicchio, V; Lamberti, P; Livrea, P

    2005-05-01

    Previously an amplitude enhancement of laser evoked potentials (LEPs) was detected during migraine attack: we further examined pain threshold to CO2 laser stimuli and LEPs during attacks, evaluating the effect of almotriptan, lysine-acetylsalicylate and placebo treatment on cutaneous hyperalgesia to thermal stimuli delivered by CO2 laser and on LEP components. Eighteen patients suffering from migraine without aura were analysed. They were divided into three groups of six patients each, randomly assigned to lysine acetyl-salicylate, almotriptan or placebo treatments. The supraorbital zones and the dorsum of the hand were stimulated on both the symptomatic and not symptomatic side in all patients. The LEPs were recorded by 25 scalp electrodes. During attacks, the P2 wave was significantly enhanced; the amplitude of the P2 component obtained by the stimulation of the supraorbital zone during the attack on the side of the headache was significantly correlated with the intensity of pain and the frequency of headache. Both almotriptan and lysine acetyl-salicylate significantly reduced the P2 amplitude but they showed no effects on hyperalgesia to laser stimulation; headache relief following therapy was correlated with the reduction of the P2 amplitude. The cortical elaboration of laser-induced experimental pain seemed increased during migraine attack, and the severity of headache was mainly related to the increase of the later LEPs components expressing the attentive and emotive compounds of suffering. Reversion of this process appeared to be primarily responsible for the efficacy of drugs in treating migraine, though both almotriptan and lysine-acetil salicilate seemed to have no effect in reducing sensitization at second and third order nociceptive neurons.

  10. 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.

  11. Therapeutic potential of TAS-102 in the treatment of gastrointestinal malignancies.

    Science.gov (United States)

    Peters, Godefridus J

    2015-11-01

    Fluoropyrimidines form the mainstay in treatment of gastrointestinal malignancies. For decades 5-fluorouracil (5FU), was the major fluoropyrimidine. Currently it is usually given in a combination with leucovorin and oxaliplatin, i.e. FOLFOX, or irinotecan, i.e. FOLFIRI, or all three, i.e. FOLFIRINOX, but gradually it has been replaced by oral fluoropyrimidine prodrug formulations, such as tegafur-uracil and S-1 (both contain ftorafur), and capecitabine (Xeloda®). Novel drugs such as the antivascular endothelial growth factor antibody, bevacizumab, and the anti-epidermal growth factor receptor antibody, cetuximab, are often combined with one of these treatment options. However, when resistance emerged, no alternatives were available. TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102's major mechanism of action is incorporation into DNA, thereby causing DNA damage. TAS-102 also follows an alternative activation pathway via thymidine kinase, and is not a substrate for dihydropyrimidine dehydrogenase. All together this explains the efficacy in 5FU-resistant models. In early clinical studies, the twice-daily schedule (5 days on, 2 days rest) for 2 weeks every 4 weeks, led to a significant disease control rate in various malignancies. This schedule showed consistent activity in two randomized trials on fluoropyrimidine refractory colorectal cancer patients, reflected by an increase of 2-3 months in overall survival in the TAS-102 group compared with placebo. Considering the impressive preclinical potential of various combinations TAS-102 has the promise to become an alternative for 5FU-resistant cancer.

  12. 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

  13. 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

  14. 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'.

  15. 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

  16. Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Edwards KL

    2015-01-01

    Full Text Available Krystal L Edwards,1 Molly G Minze2 1Ambulatory Care Division, Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX, USA; 2Ambulatory Care Division, Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, USA Introduction: As the prevalence of type 2 diabetes mellitus (T2DM is anticipated to continue to rise worldwide, so too are the treatment options also continuing to expand. Current guidelines recommend individualized treatment plans which allow for provider choice and diversity of pharmacotherapeutic regimens. The glucagon-like peptide-1 receptor agonist (GLP-1 RA class is rapidly expanding, with dulaglutide (Trulicity™ as a once-weekly agent recently approved. Aims: This article examines the evidence currently available on the efficacy and safety of dulaglutide for use in T2DM. Evidence review: Dulaglutide has been shown to have similar efficacy and safety to other newer GLP-1 RAs, and better glycemic control than placebo. It lowers glycated hemoglobin (A1c, fasting and postprandial glucose levels, and promotes weight loss when used as first-, second-, or third-line therapy. It has also been shown to improve β-cell function and provide cardiovascular benefits, such as lower blood pressure and improved lipid levels. Dulaglutide also has a low risk for hypoglycemia and a similar adverse effect profile to other GLP-1 RAs in the class, with transient gastrointestinal problems and potential risk for pancreatitis. Place in therapy: While long-term data on safety and efficacy are forthcoming, dulaglutide is positioned to be placed at the same level as other GLP-1 RAs in the class: as second-line therapy in addition to diet and exercise in those patients who cannot achieve glycemic control on monotherapy metformin. It may also be useful as first-line therapy instead of metformin. Conclusion: Dulaglutide is a once-weekly GLP-1 RA

  17. Redox potential dynamics in a grassed swale used for storage and treatment

    Science.gov (United States)

    Vorenhout, Michel; Boogaard, Floris Cornelis

    2016-04-01

    Treatment wetlands are used to remove pollutants from water. Most swales are designed to infiltrate stormwater into the subsurface. A combination of both functions can help to enhance water quality and reduce flooding risks in urban areas. The chemical forms and possible removal of pollutants such as nitrate and heavy metals in wetlands are highly dependent on the redox conditions. The redox conditions are expected to be highly dynamic and dependent on water levels and flow. We studied the correlation between these factors in an urban grassed swale system, and show that more factors play a role in these systems than water levels alone. The study system is located in the World Heritage site "Bryggen" in the city of Bergen, Norway. It consists of a series of SUDS, a socalled treatment train. The system is fed by storm water, which is at first stored in a rain garden then led to grassed swales. Water infiltrates into the subsurface in the swales. The reason for implementation of the system at this site is the protection of the highly organic archaeological layers at the site, which requires reduced conditions. Swales 1 and 2 were equipped with pressure loggers and multi-level redox and temperature probes (-2, -5, -10 and -20cm from surface). Redox and temperature probes were connected to a HYPNOS system. Measurements were taken for more than 1 year at 15 minute interval. A weather station supplemented the dataset with precipitation measurements. The redox potential in the swales show a strong correlation with water level. The regularly flooded swale 2 shows frequent anoxic events (Eh flooding events than Swale 2 and a more coarse soil with less organic matter than swale 2. These redox results are as expected given the local conditions, and show that redox conditions are localised phenomena that depend on local soil conditions. Analysis of the redox conditions during single events reveal a time lag in response to flooding events. The lag period depends on the

  18. 胰高糖素样肽1类似物治疗糖尿病的研究进展%The Progress of Glucagon-like Peptide-1 Analogue in Treatment of Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    蒋飞霞

    2011-01-01

    胰高糖素样肽1(GLP-1)是一种肠肽类激素,GLP-1不仅可促进胰岛素合成和分泌、抑制B细胞凋亡、促进B细胞增殖、抑制胰高糖素分泌;还可降低食欲,延缓胃排空;GLP-1对心血管功能产生有益作用.人GLP-1类似物适用于二甲双胍、磺脲类和(或)胰岛素增敏剂控制血糖仍不满意的2型糖尿病患者.在1型糖尿病中,GLP-1对空腹血糖的作用,取决于患者血糖、胰升糖素水平及残存胰岛B细胞功能.GLP-1能改善餐后血糖的波动,根据患者残存B细胞功能的多少,其作用机制可能有差别.%Glucagon-like peptide-l( GLP-1 ),as a gut hormone,in addition to stimulating insulin secretion and promoting pancreatic B-cell mass, GLP-1 suppresses glucagon secretion, delays gastric emptying and inhibits food intake. Their glucose-dependent mechanism limits the risk for hypoglycemia. GLP-1 improved cardiac function in humans. GLP-1 analogue is used in type 2 diabetic patients who are not sufficiently controlled by metformin and sulfonylurea. GLP-1 is able to lower fasting glycemia also in type Ⅰ diabetic patients,mainly by reducing glucagon concentrations and by remnant pancreatic B-cell secretion. The mechanism of lowering postprandial glycemia in type Ⅰ diabetic patients is different according to remnant pancreatic B-cell mass.

  19. Sensitivity of groundwater recharge using climatic analogues and HYDRUS-1D

    Directory of Open Access Journals (Sweden)

    B. Leterme

    2012-08-01

    Full Text Available The sensitivity of groundwater recharge to different climate conditions was simulated using the approach of climatic analogue stations, i.e. stations presently experiencing climatic conditions corresponding to a possible future climate state. The study was conducted in the context of a safety assessment of a future near-surface disposal facility for low and intermediate level short-lived radioactive waste in Belgium; this includes estimation of groundwater recharge for the next millennia. Groundwater recharge was simulated using the Richards based soil water balance model HYDRUS-1D and meteorological time series from analogue stations. This study used four analogue stations for a warmer subtropical climate with changes of average annual precipitation and potential evapotranspiration from −42% to +5% and from +8% to +82%, respectively, compared to the present-day climate. Resulting water balance calculations yielded a change in groundwater recharge ranging from a decrease of 72% to an increase of 3% for the four different analogue stations. The Gijon analogue station (Northern Spain, considered as the most representative for the near future climate state in the study area, shows an increase of 3% of groundwater recharge for a 5% increase of annual precipitation. Calculations for a colder (tundra climate showed a change in groundwater recharge ranging from a decrease of 97% to an increase of 32% for four different analogue stations, with an annual precipitation change from −69% to −14% compared to the present-day climate.

  20. Inhibition of ATP Synthase by Chlorinated Adenosine Analogue

    OpenAIRE

    Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

    2009-01-01

    8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing α and β subunits. Crystal structures of both α and β subunits that bind to the sub...

  1. Hydrogeochemical modelling of the Needle's Eye natural analogue (Scotland)

    International Nuclear Information System (INIS)

    First a hydrodynamic model of the natural analogue site of Needle's Eye is built with the help of the METIS code. Then the transport of the uranium is simulated from its natural deposits through sediments rich in humic facies. The use of a distribution coefficient (Kd) in the treatment of the behaviour of the solute does not make it possible to reproduce the observed concentrations. With the coupled model STELE the precipitation of UO2 in the reducing environment of the sediments can be simulated. The results agree with observations in the aqueous and the solid phase. (author)

  2. The potential role of vitamin D for prevention and treatment of tuberculosis and infectious diseases

    Directory of Open Access Journals (Sweden)

    Catia Dini

    2012-01-01

    Full Text Available INTRODUCTION: 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. RESULTS: 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. CONCLUSIONS: 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. Potential cellular and regenerative approaches for the treatment of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Emma L Lane

    2008-08-01

    Full Text Available Emma L Lane, Olivia J Handley, Anne E Rosser, Stephen B DunnettBrain Repair Group, School of Biosciences, Cardiff University, CF10 3US, UKAbstract: Parkinson’s disease is most commonly treated with a range of pharmacotherapeutics, with the more recent introduction of surgical techniques including deep-brain stimulation. These have limited capabilities to improve symptoms of the disease in more advanced stages, thus new therapeutic strategies including the use of viral vectors and stem cells are in development. Providing a continuous supply of dopamine to the striatum in an attempt to improve the treatment of motor symptoms using enzymes in the dopamine synthesis and machinery is one approach. Alternatively, there are tools which may serve to both protect and encourage outgrowth of surviving neurons using growth factors or to directly replace lost innervation by transplantation of primary tissue or stem cell-derived dopaminergic neurons. We summarize some of the potential therapeutic approaches and also consider the recent EU directives on practical aspects of handling viral vectors, cells and tissues, and in the running of clinical trials in Europe which impact on their development.Keywords: transplantation, viral vector, stem cells, ethics, European Union directive

  4. Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Davidson BA

    2014-03-01

    Full Text Available Brittany A Davidson, Angeles Alvarez Secord Division of Gynecologic Oncology, Duke Cancer Institute, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA Abstract: Epithelial ovarian cancer (EOC is the most lethal gynecological cancer. Recently, clinical trials have focused on novel antiangiogenic agents in combination with chemotherapy or alone in women with primary and recurrent ovarian cancer. Antiangiogenic agents include monoclonal antibodies, tyrosine-kinase inhibitors, and peptibodies. Many of these agents, including bevacizumab, pazopanib, nintedanib, cediranib, and trebananib, have been evaluated in randomized Phase III clinical trials, and all have demonstrated a progression-free survival (PFS benefit. Specifically, maintenance pazopanib was shown to improve PFS in women with newly diagnosed EOC. Pazopanib, an oral TKI, inhibits several kinase receptors, including those for vascular endothelial growth factor (-1,-2,-3, platelet-derived growth factor (-α and -β, and fibroblast growth factor. It also targets stem cell-factor receptor (c-kit, interleukin 2-inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase, and colony-stimulating factor 1 receptor. Pazopanib has been investigated in several Phase II and III clinical trials, with results indicating a potential role in the management of EOC. This article provides an overview of pazopanib in the treatment of EOC. Keywords: pazopanib, antiangiogenic agents, ovarian carcinoma

  5. Bioactive natural constituents from food sources-potential use in hypertension prevention and treatment.

    Science.gov (United States)

    Huang, Wu-Yang; Davidge, Sandra T; Wu, Jianping

    2013-01-01

    Prevention and management of hypertension are the major public health challenges worldwide. Uncontrolled high blood pressure may lead to a shortened life expectancy and a higher morbidity due to a high risk of cardiovascular complications such as coronary heart disease (which leads to heart attack) and stroke, congestive heart failure, heart rhythm irregularities, and kidney failure etc. In recent years, it has been recognized that many dietary constituents may contribute to human cardiovascular health. There has been an increased focus on identifying these natural components of foods, describing their physiological activities and mechanisms of actions. Grain, vegetables, fruits, milk, cheese, meat, chicken, egg, fish, soybean, tea, wine, mushrooms, and lactic acid bacteria are various food sources with potential antihypertensive effects. Their main bioactive constituents include angiotensin I-converting enzyme (ACE) inhibitory peptides, vitamins C and E, flavonoids, flavanols, cathecins, anthocyanins, phenolic acids, polyphenols, tannins, resveratrol, polysaccharides, fiber, saponin, sterols, as well as K, Ca, and P. They may reduce blood pressure by different mechanisms, such as ACE inhibition effect, antioxidant, vasodilatory, opiate-like, Ca(2+) channel blocking, and chymase inhibitory activities. These functional foods may provide new therapeutic applications for hypertension prevention and treatment, and contribute to a healthy cardiovascular population. The present review summarizes the antihypertensive food sources and their bioactive constituents, as well as physiological mechanisms of dietary products, especially focusing on ACE inhibitory activity. PMID:23627503

  6. Polymeric micellar nanocarriers of benzoyl peroxide as potential follicular targeting approach for acne treatment.

    Science.gov (United States)

    Kahraman, Emine; Özhan, Gül; Özsoy, Yıldız; Güngör, Sevgi

    2016-10-01

    The aim of this work was to optimize polymeric nano-sized micellar carriers of the anti-acne compound benzoyl peroxide (BPO) and to examine the ability of these carriers to deposit into hair follicles with the objective of improving skin delivery of BPO. BPO loaded polymeric micelles composed of Pluronic(®) F127 were prepared by the thin film hydration method and characterized in terms of size, loading capacity, morphology and physical stability. The optimized micelle formulation was then selected for skin delivery studies. The penetration of BPO loaded micellar carriers into skin and skin appendages across full thickness porcine skin was examined in vitro. Confocal microscopy images confirmed the penetration of Nile Red into hair follicles, which was loaded into micellar carriers as a model fluorescent compound. The relative safety of the polymeric micelles was evaluated with the MTT viability test using mouse embryonic fibroblasts. The results indicated that nano-sized polymeric micelles of BPO composed of Pluronic(®) F127 offer a potential approach to enhance skin delivery of BPO and that targeting of micelles into hair follicles may be an effective and safe acne treatment. PMID:27434156

  7. Polymeric micellar nanocarriers of benzoyl peroxide as potential follicular targeting approach for acne treatment.

    Science.gov (United States)

    Kahraman, Emine; Özhan, Gül; Özsoy, Yıldız; Güngör, Sevgi

    2016-10-01

    The aim of this work was to optimize polymeric nano-sized micellar carriers of the anti-acne compound benzoyl peroxide (BPO) and to examine the ability of these carriers to deposit into hair follicles with the objective of improving skin delivery of BPO. BPO loaded polymeric micelles composed of Pluronic(®) F127 were prepared by the thin film hydration method and characterized in terms of size, loading capacity, morphology and physical stability. The optimized micelle formulation was then selected for skin delivery studies. The penetration of BPO loaded micellar carriers into skin and skin appendages across full thickness porcine skin was examined in vitro. Confocal microscopy images confirmed the penetration of Nile Red into hair follicles, which was loaded into micellar carriers as a model fluorescent compound. The relative safety of the polymeric micelles was evaluated with the MTT viability test using mouse embryonic fibroblasts. The results indicated that nano-sized polymeric micelles of BPO composed of Pluronic(®) F127 offer a potential approach to enhance skin delivery of BPO and that targeting of micelles into hair follicles may be an effective and safe acne treatment.

  8. Profile of minocycline and its potential in the treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Zhang L

    2014-06-01

    Full Text Available Lulu Zhang,1,2 Jingping Zhao11Mental Health Institute of the Second Xiangya Hospital, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, 2Department of Psychology, Guangzhou First People’s Hospital, Guangzhou, Guangdong, People’s Republic of China Abstract: Accumulating evidence suggests that neuroinflammation affecting microglia plays an important role in the etiology of schizophrenia, and appropriate control of microglial activation may be a promising therapeutic strategy for schizophrenia. Minocycline, a second-generation tetracycline that inhibits microglial activation, has been shown to have a neuroprotective effect in various models of neurodegenerative disease, including anti-inflammatory, antioxidant, and antiapoptotic properties, and an ability to modulate glutamate-induced excitotoxicity. Given that these mechanisms overlap with neuropathologic pathways, minocycline may have a potential role in the adjuvant treatment of schizophrenia, and improve its negative symptoms. Here, we review the relevant studies of minocycline, ranging from preclinical research to human clinical trials.Keywords: schizophrenia, minocycline, microglia, neuroinflammation

  9. 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.

  10. Natural and Synthetic Flavonoids: Structure-Activity Relationship and Chemotherapeutic Potential for the Treatment of Leukemia.

    Science.gov (United States)

    Menezes, José C J M D S; Orlikova, Barbora; Morceau, Franck; Diederich, Marc

    2016-07-29

    Flavonoids and their derivatives are polyphenolic secondary metabolites with an extensive spectrum of pharmacological activities, including antioxidants, antitumor, anti-inflammatory, and antiviral activities. These flavonoids can also act as chemopreventive agents by their interaction with different proteins and can play a vital role in chemotherapy, suggesting a positive correlation between a lower risk of cancer and a flavonoid-rich diet. These agents interfere with the main hallmarks of cancer by various individual mechanisms, such as inhibition of cell growth and proliferation by arresting the cell cycle, induction of apoptosis and differentiation, or a combination of these mechanisms. This review is an effort to highlight the therapeutic potential of natural and synthetic flavonoids as anticancer agents in leukemia treatment with respect to the structure-activity relationship (SAR) and their molecular mechanisms. Induction of cell death mechanisms, production of reactive oxygen species, and drug resistance mechanisms, including p-glycoprotein efflux, are among the best-described effects triggered by the flavonoid polyphenol family. PMID:26463658

  11. STUDY ON THE SOMESTHETIC EVOKED POTENTIAL IN ELECTRO-ACUPUNCTURE TREATMENT OF CERVICAL SPONDYLOPATHY

    Institute of Scientific and Technical Information of China (English)

    袁青; 张洪来; 靳瑞

    2000-01-01

    In order to study the significance of somesthetic evoked potentials (SEP) in diagnosis of cervical spondylopathy (CS) and judgement of its therapeutic effect, a total of 60 cases of CS patients were randomly divided into electro-acupuncture (EA) group (n=30) and control (traction) group (n=30). Amplitudes of N9, N11, N13, N20 and intervals of N9-N13, N13-N20 andN9-N20 of SEP were used as indexes. After 3 courses of treatment, the clinical therapeutic effect of EA group was significantly superior to that of control group (P<0.01); the amplitudes of the aforementioned components of SEP in both groups increased apparently while the inter-peak latency shortened in different degrees. In EA group, the increased values of various components of SEP amplitude, except for N9, were all larger than those of control group (P<0.05 for N11, P<0.01 for N13 and N20); the values of shortened latency of different components, except for N13-N20, were all larger than those of control group (P<0.01 for N9-N13 and N9-N20). It suggests that SEP possess a certain significance in diagnosis and evaluation of CS and can be used as one of the objective indexes for evaluation of the therapeutic effect.

  12. Scum sludge as a potential feedstock for biodiesel production from wastewater treatment plants.

    Science.gov (United States)

    Wang, Yi; Feng, Sha; Bai, Xiaojuan; Zhao, Jingchan; Xia, Siqing

    2016-01-01

    The main goal of this study was to compare the component and yield of biodiesel obtained by different methods from different sludge in a wastewater treatment plant. Biodiesel was produced by ex-situ and in-situ transesterification of scum, primary and secondary sludge respectively. Results showed that scum sludge had a higher calorific value and neutral lipid than that of primary and secondary sludge. The lipid yield accounted for one-third of the dried scum sludge and the maximum yield attained 22.7% under in-situ transesterification. Furthermore the gas chromatography analysis of fatty acid methyl esters (FAMEs) revealed that all sludge contained a significant amount of palmitic acid (C16:0) and oleic acid (C18:1) regardless of extraction solvents and sludge types used. However, the difference lay in that oleic acid methyl ester was the dominant component in FAMEs produced from scum sludge while palmitic acid methyl ester was the dominant component in FAMEs from primary and secondary sludge. In addition, the percentage of unsaturated fatty acid ester in FAMEs from scum sludge accounted for 57.5-64.1% of the total esters, which was higher than the equivalent derived from primary and secondary sludge. In brief, scum sludge is a potential feedstock for the production of biodiesel and more work is needed in the future.

  13. Potential use of nanofiltration membrane in treatment of wastewater from fish and surimi industries

    Directory of Open Access Journals (Sweden)

    Wu Ta Yeong

    2002-11-01

    Full Text Available This study was carried out to determine the potential use of nanofiltration (NF membranes in treating the wastewater, generated from the fish and surimi industries. The possibility of recovering the protein from the wastewater was also investigated, since these effluents contain a large amount of protein,which could be concentrated by means of NF and recycled into the fishmeal process. The protein could also be traded as fertilizer or animal feed by-products. In this study, fish and surimi washing wastewater was generated in the laboratory. Then, the wastewater was subjected to pre-treatment by using a filter paper (due to the high concentration of suspended matter in these effluents before it was treated/separated by using a polyamide NF membrane of 500 Da. Permeation experiments showed that NF was capable of reducing COD and TSS up to 93 % and 87 %, respectively. Study on long-term flux decline indicated that polyamide NF membrane fouled much more slowly.

  14. 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.

  15. Change in haloacetic acid formation potential during UV and UV/H2O2 treatment of model organic compounds.

    Science.gov (United States)

    Sakai, Hiroshi; Autin, Olivier; Parsons, Simon

    2013-07-01

    Haloacetic acids (HAAs) are disinfection by-products produced by the chlorination of organic matter, including amino acids. Advanced oxidation processes are expected to be effective for the destruction of HAA precursors; however, recent studies have reported the possible failure of these processes to reduce HAA formation potential. This study examined HAA formation potential during the course of UV or UV/H2O2 treatment of three organic compounds: leucine, serine, and resorcinol. HAA formation potential decreased in the treatment of resorcinol, while the potential increased slightly in the treatment of serine and greatly increased for leucine. The chemical structure required for HAA formation was assumed to be produced during the course of UV/H2O2 treatment of leucine and serine. Also, H abstraction from the δ carbon was assumed to result from the initial degradation of leucine by the hydroxyl radical during the UV/H2O2 treatment. The hydroxyl radical may have further reacted with leucine moiety to shorten its carbon chain. This would have produced a chemical structure capable of forming HAA, thus increasing HAA formation potential. PMID:23415308

  16. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy.

    Science.gov (United States)

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; Dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a "safer" approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments.

  17. Hydrophobic surfactant proteins and their analogues.

    Science.gov (United States)

    Walther, Frans J; Waring, Alan J; Sherman, Mark A; Zasadzinski, Joseph A; Gordon, Larry M

    2007-01-01

    Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film enriched in surfactant lipids, hence preventing cellular collapse during respiration. Surfactant therapy using bovine or porcine lung surfactant extracts, which contain only polar lipids and native SP-B and SP-C, has dramatically improved the therapeutic outcomes of preterm infants with respiratory distress syndrome (RDS). One important goal of surfactant researchers is to replace animal-derived therapies with fully synthetic preparations based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. Here, we review recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins. Such SP-B and SP-C mimics offer the possibility of studying the mechanisms of action of the respective native proteins, and may allow the design of optimized surfactant formulations for specific pulmonary diseases (e.g., acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)). These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments. PMID:17575474

  18. Potential Impact of BioField Treatment on Atomic and Physical Characteristics of Magnesium

    OpenAIRE

    Trivedi, Mahendra; Branton, Alice; Trivedi, Dahryn; Nayak, Gopal

    2015-01-01

    Magnesium (Mg), present in every cell of all living organisms, is an essential nutrient and primarily responsible for catalytic reaction of over 300 enzymes. The aim of present study was to evaluate the effect of biofield treatment on atomic and physical properties of magnesium powder. Magnesium powder was divided into two parts denoted as control and treatment. Control part was remained as untreated and treatment part received biofield treatment. Both control and treated magnesium samples we...

  19. Potential Impact of BioField Treatment on Atomic and Physical Characteristics of Magnesium

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Magnesium (Mg), present in every cell of all living organisms, is an essential nutrient and primarily responsible for catalytic reaction of over 300 enzymes. The aim of present study was to evaluate the effect of biofield treatment on atomic and physical properties of magnesium powder. Magnesium powder was divided into two parts denoted as control and treatment. Control part was remained as untreated and treatment part received biofield treatment. Both control and treated ...

  20. Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments

    Directory of Open Access Journals (Sweden)

    Naval J

    2014-07-01

    Full Text Available Jordi Naval,1 Vicente Alonso,1,2 Miquel Angel Herranz11Genocosmetics Lab, Barcelona, Spain; 2Dermatology Unit, Hospital Nisa 9 de Octubre, Valencia, SpainIntroduction: Skin changes are among the most visible signs of aging. Skin properties such as hydration, elasticity, and antioxidant capacity play a key role in the skin aging process. Skin aging is a complex process influenced by heritable and environmental factors. Recent studies on twins have revealed that up to 60% of the skin aging variation between individuals can be attributed to genetic factors, while the remaining 40% is due to non-genetic factors. Recent advances in genomics and bioinformatics approaches have led to the association of certain single nucleotide polymorphisms (SNPs to skin properties. Our aim was to classify individuals based on an ensemble of multiple polymorphisms associated with certain properties of the skin for providing personalized skin care and anti-aging therapies.Methods and results: We identified the key proteins and SNPs associated with certain properties of the skin that contribute to skin aging. We selected a set of 13 SNPs in gene coding for these proteins which are potentially associated with skin aging. Finally, we classified a sample of 120 female volunteers into ten clusters exhibiting different skin properties according to their genotypic signature.Conclusion: This is the first study that describes the actual frequency of genetic polymorphisms and their distribution in clusters involved in skin aging in a Caucasian population. Individuals can be divided into genetic clusters defined by genotypic variables. These genotypic variables are linked with polymorphisms in one or more genes associated with certain properties of the skin that contribute to a person's perceived age. Therefore, by using this classification, it is possible to characterize human skin care and anti-aging needs on the basis of an individual's genetic signature, thus opening the door

  1. Geomagnetic properties of Proxima Centauri b analogues

    CERN Document Server

    Zuluaga, Jorge I

    2016-01-01

    The recent discovery of a planet around the closest star, Proxima Centauri, could represent a quantum leap on the testability of models in exoplanet sciences. Unlike any other discovered exoplanet, models of planetary processes in Proxima b could be contrasted against near future telescopic observations and far future in-situ measurements. In this paper we study the geomagnetic properties of Proxima b analogues, namely, solid planets with masses close but larger than Earth's mass, periods of rotation of several days and habitable surface conditions. Assuming different planetary masses, bulk compositions and periods of rotations, we calculate for each planetary analogue its radius, heat flux, time of inner core formation, dynamo lifetime and minimum dipole magnetic moment. We find that most ($\\gtrsim$70\\%) Proxima b analogues develop intrinsic dynamos that last at least 3 Gyr, although only half of them are older than the present age of the host star ($4-6$ Gyr). Relying in our planetary evolution models, we p...

  2. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem A.

    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.

  3. LHRH analogue as a depot preparation (Zoladex) in the treatment of advanced carcinoma of the prostate followed by orchiectomy as a second line therapy--a phase II study

    DEFF Research Database (Denmark)

    Iversen, P; Rose, C; Stage, J G;

    1989-01-01

    An LHRH agonist, Zoladex, was employed as a monthly depot in 56 previously untreated patients with advanced carcinoma of the prostate. Of 53 evaluable patients, 27 achieved partial remission and 7 were stable. Median duration of response was 10 months. A favorable subjective response was attained...... orchiectomy following treatment failure of Zoladex. In one patient partial remission according to protocol criteria was recorded. Treatment with LHRH agonists seems safe and may serve as an alternative to conventional hormonal treatment of advanced carcinoma of the prostate....

  4. Acupuncture: a potential modality for the treatment of auricular pruritus in Ramsay Hunt Syndrome with multiple cranial nerve lesions.

    Science.gov (United States)

    Liu, Lan Ying; Wang, He Sheng; Sun, Jian Hua

    2015-03-01

    Auricular pruritus coexisted with multiple cranial nerve lesions in Ramsay Hunt syndrome has been rarely reported in the literature especially its treatment. However, auricular pruritus cannot be better improved along with the improvement of multiple cranial nerve lesions. We tried to solve the problem with acupuncture and got experience from it. The following 2 cases of Ramsay Hunt syndrome show a potential modality for the treatment of auricular pruritus with acupuncture.

  5. Potential for leaching of arsenic from excavated rock after different drying treatments.

    Science.gov (United States)

    Li, Jining; Kosugi, Tomoya; Riya, Shohei; Hashimoto, Yohey; Hou, Hong; Terada, Akihiko; Hosomi, Masaaki

    2016-07-01

    Leaching of arsenic (As) from excavated rock subjected to different drying methods is compared using sequential leaching tests and rapid small-scale column tests combined with a sequential extraction procedure. Although the total As content in the rock was low (8.81 mg kg(-1)), its resulting concentration in the leachate when leached at a liquid-to-solid ratio of 10 L kg(-1) exceeded the environmental standard (10 μg L(-1)). As existed mainly in dissolved forms in the leachates. All of the drying procedures applied in this study increased the leaching of As, with freeze-drying leading to the largest increase. Water extraction of As using the two tests showed different leaching behaviors as a function of the liquid-to-solid ratio, and achieved average extractions of up to 35.7% and 25.8% total As, respectively. Dissolution of As from the mineral surfaces and subsequent re-adsorption controlled the short-term release of As; dissolution of Fe, Al, and dissolved organic carbon played important roles in long-term As leaching. Results of the sequential extraction procedure showed that use of 0.05 M (NH4)2SO4 underestimates the readily soluble As. Long-term water extraction removed almost all of the non-specifically sorbed As and most of the specifically sorbed As. The concept of pollution potential indices, which are easily determined by the sequential leaching test, is proposed in this study and is considered for possible use in assessing efficacy of treatment of excavated rocks. PMID:27058919

  6. Potential for gamma-radiation as a quarantine treatment for Caribbean fruit fly in citrus

    International Nuclear Information System (INIS)

    The potential for using gamma-radiation as a quarantine treatment for the control of the Caribbean fruit fly (Anastrepha suspensa [Loew]) in citrus is being investigated by the Agricultural Research Service of the U.S. Department of Agriculture and the Florida Department of Citrus in cooperation with the U.S. Department of Energy and private industry. In dosage-mortality tests, pupae were recovered from infested grapefruits held at 250C for six weeks following irradiation at 0.l5 and 0.30 kGy. No insects were recovered from grapefruit irradiated at 0.60 and 0.90 kGy. Two adults emerged from the recovered pupae, one male at 0.15 kGy and one female at 0.30 kGy; both adults died without reproducing. Based on the number of pupae recovered, fly mortality was 98.9 percent at 0.l5 kGy percent at 0.30 kGy, and l00 percent at 60 and 90 kGy. In phytotoxicity tests, noninfested grapefruits were held for four weeks at l0 or l60C, followed by two weeks at 2l0C, and then examined for radiation injury. Injury was minimal at 0.30 kGy, and the grapefruit had acceptable taste, no adverse chemical changes, and met Grade A standards when examined by Florida inspectors. Injury to the rind and off-flavors in juice and sections were often severe at higher dosages (0.60 and 0.90 kGy). Grapefruit irradiated at 0.60 and 0.90 kGy) showed rind breakdown and scald after storage. Scald was the dominant injury in October and December tests, and rind breakdown was the dominant injury in February, April, and May tests. Generally, injured areas developed decay during holding at 2l0C

  7. Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia: The HypoAna trial

    DEFF Research Database (Denmark)

    Agesen, R M; Kristensen, P L; Beck-Nielsen, H;

    2016-01-01

    the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. CONCLUSION: In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non...

  8. Classical Simulated Annealing Using Quantum Analogues

    Science.gov (United States)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-06-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  9. Classical Simulated Annealing Using Quantum Analogues

    Science.gov (United States)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-08-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  10. Improving the Efficiency of a Coagulation-Flocculation Wastewater Treatment of the Semiconductor Industry through Zeta Potential Measurements

    OpenAIRE

    Eduardo Alberto López-Maldonado; Mercedes Teresita Oropeza-Guzmán; Adrián Ochoa-Terán

    2014-01-01

    Efficiency of coagulation-flocculation process used for semiconductor wastewater treatment was improved by selecting suitable conditions (pH, polyelectrolyte type, and concentration) through zeta potential measurements. Under this scenario the zeta potential, ζ, is the right parameter that allows studying and predicting the interactions at the molecular level between the contaminants in the wastewater and polyelectrolytes used for coagulation-flocculation. Additionally, this parameter is a k...

  11. Potential Cost-Effectiveness of Schistosomiasis Treatment for Reducing HIV Transmission in Africa – The Case of Zimbabwean Women

    OpenAIRE

    Ndeffo Mbah, Martial L.; Poolman, Eric M.; Katherine E Atkins; Evan W Orenstein; Lauren Ancel Meyers; Jeffrey P Townsend; Alison P Galvani

    2013-01-01

    BACKGROUND: Epidemiological data from Zimbabwe suggests that genital infection with Schistosoma haematobium may increase the risk of HIV infection in young women. Therefore, the treatment of Schistosoma haematobium with praziquantel could be a potential strategy for reducing HIV infection. Here we assess the potential cost-effectiveness of praziquantel as a novel intervention strategy against HIV infection. METHODS: We developed a mathematical model of female genital schistosomiasis (FGS) and...

  12. Analogues of neuroactive polyamine wasp toxins that lack inner basic sites exhibit enhanced antagonism toward a muscle-type mammalian nicotinic acetylcholine receptor

    DEFF Research Database (Denmark)

    Stromgaard, K; Brierley, M J; Andersen, K;

    1999-01-01

    properties (stepwise macroscopic pK(a) values) were determined by (13)C NMR titrations. All analogues are fully protonated at physiological pH. The effects of these compounds on acetylcholine-induced currents in TE671 cells clamped at various holding potentials were determined. All of the analogues...... noncompetitively antagonized the nicotinic acetylcholine receptor (nAChR) in a concentration-, time-, and voltage-dependent manner. The amplitudes of acetylcholine-induced currents were compared at their peaks and at the end of a 1 s application in the presence or absence of the analogues. Most of the analogues...

  13. Effect of Phytase Treatment on Phosphate Availability in the Potential Food Supplement Corn Distillers’ Grains with Solubles

    OpenAIRE

    Thomas P. West

    2014-01-01

    The most effective treatment of the potential food supplement corn distillers’ grains with solubles using a fungal phytase to degrade phytic acid and release phosphorus was explored. Compared to the untreated grains with solubles, the phytic acid level in the grains with solubles was reduced by phytase treatment but treatment with 4 units of enzyme/g was more effective than 2 units of enzyme/g after 2 h. At 30°C or 45°C, 4 units of phytase/g reduced the phytic acid content of the grains with ...

  14. Incretin hormones and maturity onset diabetes of the young - pathophysiological implications and anti-diabetic treatment potential

    DEFF Research Database (Denmark)

    Østoft, Signe Harring

    2015-01-01

    . The objectives of this thesis were to study the pathophysiology of GCK-diabetes and HNF1A-diabetes by investigating the incretin effect, the physiological response to food ingestion and to estimate the treatment potential of a glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with HNF1A-diabetes......-blind, crossover trial investigating the glucose lowering effect and risk of hypoglycaemia during 6 weeks of treatment with the GLP-1RA, liraglutide compared to the SU, glimepiride in 16 patients with HNF1A-diabetes. At baseline and at the end of each treatment period a standardised meal test followed by a light...... demonstrated according to insulin and glucagon responses and gastric emptying, and counter-regulatory responses were preserved during both treatments. No effect of either treatment was seen on fructosamine or HbA1c. In conclusion, patients with GCK-diabetes show normal incretin and glucagon physiology, thus...

  15. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

    DEFF Research Database (Denmark)

    Köhler, Karl Ole; Krogh, Jesper; Mors, Ole;

    2016-01-01

    the association between inflammation and depression together with the current evidence on use of anti-inflammatory treatment in depression. Based on this, we address the questions and challenges that seem most important and relevant to future studies, such as timing, most effective treatment lengths......Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular......, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity...

  16. ANTIPSYCHOTIC SIDE-EFFECT – POTENTIAL RISK OF PATIENTS REJECTING THEIR TREATMENTS

    OpenAIRE

    Dadić-Hero, Elizabeta; Ružić, Klementina; Medved, Paola; Tatalović-Vorkapić, Sanja; Graovac, Mirjana

    2010-01-01

    Antipsychotics side-effects pose an enormous problem in psychiatric treatment. The choice of antipsychotics is a crucial issue in the treatment as both patients' cooperation and compliance often depend upon it. Severe side-effects might sometimes cause the treatment interruption, to which each patient is entitled. Schizotypal personality disorder (SPD) features include social and interpersonal deficits, discomfort with close relationships, as well as cognitive and perceptual distorti...

  17. The Potential Contribution of Mass Treatment to the Control of Plasmodium falciparum Malaria

    OpenAIRE

    Lucy C Okell; Griffin, Jamie T.; Immo Kleinschmidt; T Déirdre Hollingsworth; Churcher, Thomas S.; White, Michael J.; Teun Bousema; Drakeley, Chris J; Azra C Ghani

    2011-01-01

    Mass treatment as a means to reducing P. falciparum malaria transmission was used during the first global malaria eradication campaign and is increasingly being considered for current control programmes. We used a previously developed mathematical transmission model to explore both the short and long-term impact of possible mass treatment strategies in different scenarios of endemic transmission. Mass treatment is predicted to provide a longer-term benefit in areas with lower malaria transmis...

  18. 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.

  19. Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance.

    Science.gov (United States)

    Wiśniewski, Kazimierz; Sueiras-Diaz, Javier; Jiang, Guangcheng; Galyean, Robert; Lu, Mark; Thompson, Dorain; Wang, Yung-Chih; Croston, Glenn; Posch, Alexander; Hargrove, Diane M; Wiśniewska, Halina; Laporte, Régent; Dwyer, John J; Qi, Steve; Srinivasan, Karthik; Hartwig, Jennifer; Ferdyan, Nicky; Mares, Monica; Kraus, John; Alagarsamy, Sudarkodi; Rivière, Pierre J M; Schteingart, Claudio D

    2016-04-14

    Glucagon-like peptide-2 receptor agonists have therapeutic potential for the treatment of intestinal diseases. The native hGLP-2, a 33 amino acid gastrointestinal peptide, is not a suitable clinical candidate, due to its very short half-life in humans. In search of GLP-2 receptor agonists with better pharmacokinetic characteristics, a series of GLP-2 analogues containing Gly substitution at position 2, norleucine in position 10, and hydrophobic substitutions in positions 11 and/or 16 was designed and synthesized. In vitro receptor potency at the human GLP-2, selectivity vs the human GLP-1 and GCG receptors, and PK profile in rats were determined for the new analogues. A number of compounds more potent at the hGLP-2R than the native hormone, showing excellent receptor selectivity and very low systemic clearance (CL) were discovered. Analogues 69 ([Gly(2),Nle(10),d-Thi(11),Phe(16)]hGLP-2-(1-30)-NH2), 72 ([Gly(2),Nle(10),d-Phe(11),Leu(16)]hGLP-2-(1-33)-OH), 73 ([Gly(2),Nle(10),d-Phe(11),Leu(16)]hGLP-2-(1-33)-NH2), 81 ([Gly(2),Nle(10),d-Phe(11),Leu(16)]hGLP-2-(1-33)-NHEt), and 85 ([Gly(2),Nle(10),d-Phe(11),Leu(16)]hGLP-2-(1-33)-NH-((CH2)2O)4-(CH2)2-CONH2) displayed the desired profiles (EC50 (hGLP-2R) < 100 pM, CL in rat <0.3 mL/min/kg, selective vs hGLP-1R and hGCGR). Compound 73 (FE 203799) was selected as a candidate for clinical development. PMID:26986178

  20. Quinine conjugates and quinine analogues as potential antimalarial agents.

    Science.gov (United States)

    Jones, Rachel A; Panda, Siva S; Hall, C Dennis

    2015-06-01

    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.

  1. Subsurface Halophiles: An Analogue for Potential Life on Mars.

    OpenAIRE

    Woolman, P. F.; Pearson, V. K.; Cockell, C.; Olsson-Francis, K.

    2015-01-01

    Recent discoveries have reopened the idea that, in the past, Mars had a period of wetness where conditions were similar to those on Earth [1]. If this was the case then it is feasible that these environments may have harboured life. The martian surface today is dry, cold and heavily bombarded by UV radiation, making it an environment unsuitable for any known terrestrial life [2]; the martian subsurface might be considerably more hospitable. Subsurface microbial communities would not have acce...

  2. An Analogue of the Antibiotic Teicoplanin Prevents Flavivirus Entry In Vitro

    NARCIS (Netherlands)

    De Burghgraeve, Tine; Kaptein, Suzanne J. F.; Ayala Nunez, Vanesa; 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 dose-d

  3. 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....

  4. Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis.

    Science.gov (United States)

    Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

    2015-12-01

    Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective. PMID:26343337

  5. Targeting EGFR and COX-2 as a potential treatment improvement strategy in cancer radiotherapy

    International Nuclear Information System (INIS)

    Molecular targeting, i.e. use of agents that counteract molecular processes that are dysregulated in cancer cells, which may be responsible for tumor radio-or chemoresistance, is a recently extensively investigated approach to further improve radiotherapy, chemotherapy or radiochemotherapy. Many potential targets for augmentation of radio (or chemo) response have been identified including epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2) enzyme, mutated ras and angiogenic molecules. Agents that selectively inhibit these molecules are becoming available at a rapid rate, and many of them have been shown in preclinical testing to be highly effective in improving tumor radioresponse or chemoresponse, without significantly affecting normal tissues. The interaction of EGFR and COX-2 inhibitors with radiation has attracted a flare of investigational interest, and is over-viewed here. EGFR is frequently overexpressed or mutated in many types of cancer, which is associated with more aggressive tumor behavior and poorer tumor response to cytotoxic agents, including radiation. Blockade of EGFR or interference with its downstream signaling processes can improve tumor treatment. Our own studies, using human tumor xenografts, demonstrated that blocking EGFR with C225 anti-EGFR antibody produces a dramatic enhancement of tumor radioresponse, and even more dramatic response when radiation is combined with chemotherapeutic agents. C225 acts by a number of mechanisms including inhibition of DNA repair from radiation damage, enhancement of apoptosis and tumor necrosis, and by inhibition of tumor angiogenesis. Inhibition of tyrosine kinase activation by small molecule agents, such as Iressa or Tarceva, is another approach in interfering with EGFR-signaling, which also showed potent enhancing effect on tumor radioresponse. There are two COX enzymes: COX-1 and COX-2. While COX-1 is a ubiquitous constitutive enzyme having housekeeping physiological function, COX-2 is an

  6. L-DOPA treatment in MPTP-mouse model of Parkinson's disease potentiates homocysteine accumulation in substantia nigra.

    Science.gov (United States)

    Bhattacharjee, Nivedita; Mazumder, Muhammed Khairujjaman; Paul, Rajib; Choudhury, Amarendranath; Choudhury, Sabanum; Borah, Anupom

    2016-08-15

    One of the intermediates of methionine cycle, the homocysteine (Hcy), elevates in plasma of Parkinson's disease (PD) patients undergoing L-DOPA (3,4-dihydroxyphenylalanine) therapy and has been regarded as a risk factor of the disease. Several evidences pointed out that Hcy causes degeneration of dopaminergic neurons. In rodent, elevated level of Hcy in brain or infusion of the same directly into the substantia nigra (SN) potentiates dopaminergic neurodegeneration. However, the influence of L-DOPA therapy on the levels of Hcy in dopamine-rich regions of the brain (striatum and SN) of experimental models of PD is not known. The present study, for the first time, tested the hypothesis that L-DOPA treatment in experimental mouse model of PD potentiates Hcy accumulation in the dopamine-rich regions of the brain. We found a significant elevation of Hcy level in nigrostriatum in naïve as well as parkinsonian mice as a result of chronic L-DOPA treatment. Interestingly, L-DOPA treatment significantly elevates Hcy level in nigra but not in striatum of parkinsonian mice, when compared with L-DOPA naïve group. However, there is no significant decrease in the number of dopaminergic neurons in SN region in the parkinsonian mice given L-DOPA treatment. Thus, the present study demonstrates that L-DOPA treatment potentiates the level of Hcy in the SN without causing aggravated neurodegeneration in parkinsonian mice model.

  7. Thermophilic sludge digestion improves energy balance and nutrient recovery potential in full-scale municipal wastewater treatment plants.

    Science.gov (United States)

    De Vrieze, Jo; Smet, Davey; Klok, Jacob; Colsen, Joop; Angenent, Largus T; Vlaeminck, Siegfried E

    2016-10-01

    The conventional treatment of municipal wastewater by means of activated sludge is typically energy demanding. Here, the potential benefits of: (1) the optimization of mesophilic digestion; and (2) transitioning to thermophilic sludge digestion in three wastewater treatment plants (Tilburg-Noord, Land van Cuijk and Bath) in the Netherlands is evaluated, including a full-scale trial validation in Bath. In Tilburg-Noord, thermophilic sludge digestion covered the energy requirements of the plant (102%), whereas 111% of sludge operational treatment costs could be covered in Bath. Thermophilic sludge digestion also resulted in a strong increase in nutrient release. The potential for nutrient recovery was evaluated via: (1) stripping/absorption of ammonium; (2) autotrophic removal of ammonium via partial nitritation/anammox; and (3) struvite precipitation. This research shows that optimization of sludge digestion may lead to a strong increase in energy recovery, sludge treatment costs reduction, and the potential for advanced nutrient management in full-scale sewage treatment plants. PMID:27423372

  8. Potentials of type I interferon therapy in the treatment of pancreatic cancer

    NARCIS (Netherlands)

    S. Booij (Stephanie)

    2015-01-01

    markdownabstract__Abstract__ Pancreatic cancer is a highly aggressive malignancy with limited treatment options. Over the last 30 years survival rates have barely been approved and research has focused on other treatment modalities like biological modulators such as type I interferons (IFNs). A few

  9. Artemisia annua L. as a plant with potential use in the treatment of acanthamoebiasis.

    Science.gov (United States)

    Derda, Monika; Hadaś, Edward; Cholewiński, Marcin; Skrzypczak, Łukasz; Grzondziel, Anna; Wojtkowiak-Giera, Agnieszka

    2016-04-01

    The treatment of acanthamoebiasis is a great problem. Most cerebral invasions end with death, and the treatment of ocular invasions is usually long-lasting and not very effective. Numerous plant extracts and substances isolated from plants, which are effective against trophozoites or cysts, have been studied in the treatment of acanthamoebiasis. However, no agents that are simultaneously effective against both developing forms of amoebae have been discovered yet. It seems that such a plant which fulfils both tasks is Artemisia annua L. Our studies showed that water, alcohol and chloroform extracts from the herb A. annua L. can be applied in general and local treatment or in combined therapy with antibiotics in the treatment of acanthamoebiasis. Extracts from this plant show not only in vitro but also in vivo effects. Studies carried out on experimental animals infected with amoebae show that the application of these extracts significantly prolongs the survival of the animals. PMID:26782959

  10. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

    DEFF Research Database (Denmark)

    Köhler, Ole; Krogh, Jesper; Mors, Ole;

    2016-01-01

    Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular......, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity of...... the inflammatory cascade, limited clinical evidence, and the risk for side effects stress cautiousness before clinical application. Thus, despite proof-of-concept studies of anti-inflammatory treatment effects in depression, important challenges remain to be investigated. Within this paper, we review...

  11. Synthesis and antimicrobial activity of squalamine analogue.

    Science.gov (United States)

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

  12. Somatostatin analogue scintigraphy and tuberculosis: case report

    International Nuclear Information System (INIS)

    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)

  13. 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 mol

  14. The glaciogenic reservoir analogue studies project (GRASP)

    DEFF Research Database (Denmark)

    Moscariello, A.; Moreau, Julien; Vegt, P. van der;

    increasing the risk associated with developing effectively these reservoirs. Therefore a analogue-based predictive stratigraphical and sedimentological model can help to steer drilling strategy and reduce uncertainties and associated risks. For this purpose the GRASP joint industry programme was established...

  15. Phosphate analogues in the dissection of mechanism.

    OpenAIRE

    Heidi J. Korhonen; Conway, Louis P.; Hodgson, David R. W.

    2014-01-01

    Phosphoryl group transfer is central to genetic replication, cellular signalling and many metabolic processes. Understanding the mechanisms of phosphorylation and phosphate ester and anhydride cleavage is key to efforts towards biotechnological and biomedical exploitation of phosphate-handling enzymes. Analogues of phosphate esters and anhydrides are indispensable tools, alongside protein mutagenesis and computational methods, for the dissection of phosphoryl transfer mechanisms. Hydrolysable...

  16. Chemically synthesized dicarba H2 relaxin analogues retain strong RXFP1 receptor activity but show an unexpected loss of in vitro serum stability.

    Science.gov (United States)

    Hossain, Mohammed Akhter; Haugaard-Kedström, Linda M; Rosengren, K Johan; Bathgate, Ross A D; Wade, John D

    2015-11-28

    Peptides and proteins are now acknowledged as viable alternatives to small molecules as potential therapeutic agents. A primary limitation to their more widespread acceptance is their generally short in vivo half-lives due to serum enzyme susceptibility and rapid renal clearance. Numerous chemical approaches to address this concern have been undertaken in recent years. The replacement of disulfide bonds with non-reducible elements has been demonstrated to be one effective means by eliminating the deleterious effect of serum reductases. In particular, substitution with dicarba bonds via ring closure metathesis has been increasingly applied to many bioactive cystine-rich peptides. We used this approach for the replacement of the A-chain intramolecular disulfide bond of human relaxin 2 (H2 relaxin), an insulin-like peptide that has important regulatory roles in cardiovascular and connective tissue homeostasis that has led to successful Phase IIIa clinical trials for the treatment of acute heart failure. Use of efficient solid phase synthesis of the two peptide chains was followed by on-resin ring closure metathesis and formation of the dicarba bond within the A-chain and then by off-resin combination with the B-chain via sequential directed inter-chain disulfide bond formation. After purification and comprehensive chemical characterization, the two isomeric synthetic H2 relaxin analogues were shown to retain near-equipotent RXFP1 receptor binding and activation propensity. Unexpectedly, the in vitro serum stability of the analogues was greatly reduced compared with the native peptide. Circular dichroism spectroscopy studies showed subtle differences in the secondary structures between dicarba analogues and H2 relaxin suggesting that, although the overall fold is retained, it may be destabilized which could account for rapid degradation of dicarba analogues in serum. Caution is therefore recommended when using ring closure metathesis as a general approach to enhance

  17. Alternative curved-boundary treatment for the lattice Boltzmann method and its application in simulation of flow and potential fields.

    Science.gov (United States)

    Mohammadipoor, O R; Niazmand, H; Mirbozorgi, S A

    2014-01-01

    Since the lattice Boltzmann method originally carries out the simulations on the regular Cartesian lattices, curved boundaries are often approximated as a series of stair steps. The most commonly employed technique for resolving curved-boundary problems is extrapolating or interpolating macroscopic properties of boundary nodes. Previous investigations have indicated that using more than one equation for extrapolation or interpolation in boundary conditions potentially causes abrupt changes in particle distributions. Therefore, a curved-boundary treatment is introduced to improve computational accuracy of the conventional stair-shaped approximation used in lattice Boltzmann simulations by using a unified equation for extrapolation of macroscopic variables. This boundary condition is not limited to fluid flow and can be extended to potential fields. The proposed treatment is tested against several well-established problems and the solutions order of accuracy is evaluated. Numerical results show that the present treatment is of second-order accuracy and has reliable stability characteristics. PMID:24580362

  18. Facile synthesis of N-6 adenosine modified analogue toward S-adenosyl methionine derived probe for protein arginine methyltransferases

    Institute of Scientific and Technical Information of China (English)

    Wei Hong; James Dowden

    2011-01-01

    Chemically modified cellular co-factors that provide function, such as immobilization or incorporation of fluorescent dyes, are valuable probes of biological activity. A convenient route to obtain S-adenosyl methionine (AdoMet) analogues modified at N-6 adenosine to feature a linker terminating in azide functionality is described herein. Subsequent decoration of such AdoMet analogues with guanidinium terminated linkers leads to novel potential bisubstrate inhibitors for protein arginine methyltransferases, PRMTs.

  19. Preserved to preservative free prostaglandin analogues in primary open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Asha S. Morge

    2013-12-01

    POAG develops gradually and take long time to get detected and require long term treatment with topical prostaglandin analogues (PGF2 which is the most common as well as most widely used drugs. These PGF2 analogues need to be taken for longer time and more prone to develop adverse drug reactions. Common ADR seen with PG analogues are irritation on instillation, foreign body sensation, dryness of eyes, pain in eye, increased pigmentation of iris, increased eyelash growth, changes in periorbital sulcus and fat. Some ADRs (Adverse Drug Reaction are explained by the inherent properties of Prostaglandins and those are not explained are because of preservative used in medication and these ADRs can be minimised by using preservative free drug like Tafluprost which are having same efficacy in decreasing IOP. [Int J Basic Clin Pharmacol 2013; 2(6.000: 696-704

  20. 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

  1. Eco-Friendly Insecticide Discovery via Peptidomimetics: Design, Synthesis, and Aphicidal Activity of Novel Insect Kinin Analogues.

    Science.gov (United States)

    Zhang, Chuanliang; Qu, Yanyan; Wu, Xiaoqing; Song, Dunlun; Ling, Yun; Yang, Xinling

    2015-05-13

    Insect kinin neuropeptides are pleiotropic peptides that are involved in the regulation of hindgut contraction, diuresis, and digestive enzyme release. They share a common C-terminal pentapeptide sequence of Phe(1)-Xaa(2)-Yaa(3)-Trp(4)-Gly(5)-NH2 (where Xaa(2) = His, Asn, Phe, Ser, or Tyr; Yaa(3) = Pro, Ser, or Ala). Recently, the aphicidal activity of insect kinin analogues has attracted the attention of researchers. Our previous work demonstrated that the sequence-simplified insect kinin pentapeptide analogue Phe-Phe-[Aib]-Trp-Gly-NH2 could retain good aphicidal activity and be the lead compound for the further discovery of eco-friendly insecticides which encompassed a broad array of biochemicals derived from micro-organisms and other natural sources. Using the peptidomimetics strategy, we chose Phe-Phe-[Aib]-Trp-Gly-NH2 as the lead compound, and we designed and synthesized three series, including 31 novel insect kinin analogues. The aphicidal activity of the new analogues against soybean aphid was determined. The results showed that all of the analogues exhibited aphicidal activity. Of particular interest was the analogue II-1, which exhibited improved aphicidal activity with an LC50 of 0.019 mmol/L compared with the lead compound (LC50 = 0.045 mmol/L) or the commercial insecticide pymetrozine (LC50 = 0.034 mmol/L). This suggests that the analogue II-1 could be used as a new lead for the discovery of potential eco-friendly insecticides. PMID:25912216

  2. Complementary Therapies for Significant Dysfunction from Tinnitus: Treatment Review and Potential for Integrative Medicine

    Directory of Open Access Journals (Sweden)

    Ruth Q. Wolever

    2015-01-01

    Full Text Available Tinnitus is a prevalent and costly chronic condition; no universally effective treatment exists. Only 20% of patients who report tinnitus actually seek treatment, and when treated, most patients commonly receive sound-based and educational (SBE therapy. Additional treatment options are necessary, however, for nonauditory aspects of tinnitus (e.g., anxiety, depression, and significant interference with daily life and when SBE therapy is inefficacious or inappropriate. This paper provides a comprehensive review of (1 conventional tinnitus treatments and (2 promising complementary therapies that have demonstrated some benefit for severe dysfunction from tinnitus. While there has been no systematic study of the benefits of an Integrative Medicine approach for severe tinnitus, the current paper reviews emerging evidence suggesting that synergistic combinations of complementary therapies provided within a whole-person framework may augment SBE therapy and empower patients to exert control over their tinnitus symptoms without the use of medications, expensive devices, or extended programs.

  3. Steam-treatment-based soil remediation promotes heat-tolerant, potentially pathogenic microbiota

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Bender, Mikkel; Ekelund, Flemming;

    2014-01-01

    We investigated microbiota in surface and subsurface soil from a site, above steam-treated deep sub-soil originally contaminated with chlorinated solvents. During the steam treatment, the surface soil reached temperatures c. 30°C higher than the temperature in untreated soil; whereas the subsurface...... are rarely detected in Danish soils but high numbers (c. 105 hyphal forming units g−1) occurred in the treated soil up to 31 months after the steam-treatment. We conclude that steam-treatment leads to changes of the microbial communities. Some changes are temporary while others can last for years after...... termination of the steam-treatment; reflecting different strategies that soil microorganisms follow....

  4. Recent advances in topoisomerase I-targeting agents, camptothecin analogues.

    Science.gov (United States)

    Kim, Dae-Kee; Lee, Namkyu

    2002-12-01

    The present review concentrates on camptothecin (CPT) analogues, the most extensively studied topoisomerase I (topo I) inhibitors, and provides concise information on the structural features of human topo I enzyme, mechanisms of interaction of CPT with topo I, structure-activity relationship study of CPT analogues including the influence of lactone stability on antitumor activity, and recent updates of valuable CPT analogues. PMID:12370044

  5. Constructed Wetlands: Potential for their Use in Treatment of Grey Water in Kenya.

    OpenAIRE

    Kamau, Cynthia Gitiri

    2009-01-01

    Constructed wetlands are cost-effective, nature oriented alternatives for wastewater treatment that have gained acceptance worldwide. For Kenyan small communities in particular, constructed wetlands offer opportunities for wastewater reuse and resource recovery as well as improvements in local environmental health conditions. These communities generally lack conventional centralized waste water treatment systems. This thesis aims to identify peri- urban and rural areas suitable for the establ...

  6. Recurrent herpes simplex infections: laser therapy as a potential tool for long-term successful treatment

    Directory of Open Access Journals (Sweden)

    Dennis Carvalho Ferreira

    2011-06-01

    Full Text Available Herpes simplex virus types 1 and 2 are the main infectious agents associated with oral and genital ulcerations. These infections are now widely recognized as sexually transmitted diseases. Among treatment options, low-level laser therapy (LLLT has shown promising clinical results as a longer-lasting suppression therapy. Two clinical cases are described with recurrent labial herpes for which LLLT was used. Following treatment, both patients remained symptom free during the 17-month clinical follow-up period.

  7. Topical treatment in vitiligo and the potential uses of new drug delivery systems

    OpenAIRE

    Garg Bhawna; Saraswat Abir; Bhatia Amit; Katare Om

    2010-01-01

    Vitiligo is a psychologically devastating condition. Topical therapy is employed as first-line treatment in localized vitiligo. Currently, several topical agents are available in many forms viz. methoxsalen (solution and cream), trioxsalen (solution), corticosteroids (gel, cream, ointment and solution) and calcineurin inhibitors (ointment and cream). Although topical therapy has an important position in vitiligo treatment, side-effects or poor efficacy affect their utility and patient complia...

  8. Potential Impact of Biofield Energy Treatment on the Atomic, Physical and Thermal Properties Indium Powder

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Indium has gained significant attention in the semiconductor industries due to its unique thermal and optical properties. The objective of this research was to investigate the influence of the biofield energy treatment on the atomic, physical and thermal properties of the indium. The study was performed in two groups (control and treated). The control group remained as untreated, and treated group received Mr. Trivedi’s biofield energy treatment. Subsequently, the control and treated in...

  9. Biofield treatment: A potential strategy for modification of physical and thermal properties of indole

    OpenAIRE

    Trivedi, Mahendra; Branton, Alice; Trivedi, Dahryn; Nayak, Gopal

    2015-01-01

    Indole compounds are important class of therapeutic molecules, which have excellent pharmaceutical applications. The objective of present research was to investigate the influence of biofield treatment on physical and thermal properties of indole. The study was performed in two groups (control and treated). The control group remained as untreated, and biofield treatment was given to treated group. The control and treated samples were characterized by X-ray diffraction (XRD), differential scan...

  10. [Limiting factors in the class III camouflage treatment: a potential protocol].

    Science.gov (United States)

    Chaques Asensi, José

    2016-06-01

    The Class III skeletal malocclusion has been traditionally treated with a combined approach of orthodontics and orthognathic surgery or with a strategy of orthodontic camouflage. Some severe cases can be identified as ideal candidates for a surgical treatment whereas some others can be handled with orthodontics alone, with a reasonable expectation of an acceptable result. However, the problem remains for the borderline patient. In fact, limited information is available in the literature regarding the identification of the factors that can help in establishing the limits for one treatment modality or the other. Furthermore, the quantification of some of these factors, for practical purposes, is practically missing or very seldom suggested. Therefore, the decision making process remains a subjective reflection based on the "good clinical sense" of the orthodontist or just reduced to an "educated guess". In order to add some information, hopefully useful in deciding the most suitable treatment option for the individual patient, we propose a clinical protocol based on four different factors. Namely: the skeletal discrepancy, the occlusal discrepancy, the periodontal condition and facial aesthetics. For each one of these factors several parameters will be evaluated and, for some of them, an attempt to provide some reference numerical values will be made. Finally, clinical examples will be presented to illustrate the concepts discussed and the treatment alternatives, final treatment plan and treatment outcome will be analyzed for each one of them. PMID:27358006

  11. Metagenomic analysis of an ecological wastewater treatment plant's microbial communities and their potential to metabolize pharmaceuticals.

    Science.gov (United States)

    Balcom, Ian N; Driscoll, Heather; Vincent, James; Leduc, Meagan

    2016-01-01

    Pharmaceuticals and other micropollutants have been detected in drinking water, groundwater, surface water, and soil around the world. Even in locations where wastewater treatment is required, they can be found in drinking water wells, municipal water supplies, and agricultural soils. It is clear conventional wastewater treatment technologies are not meeting the challenge of the mounting pressures on global freshwater supplies. Cost-effective ecological wastewater treatment technologies have been developed in response. To determine whether the removal of micropollutants in ecological wastewater treatment plants (WWTPs) is promoted by the plant-microbe interactions, as has been reported for other recalcitrant xenobiotics, biofilm microbial communities growing on the surfaces of plant roots were profiled by whole metagenome sequencing and compared to the microbial communities residing in the wastewater. In this study, the concentrations of pharmaceuticals and personal care products (PPCPs) were quantified in each treatment tank of the ecological WWTP treating human wastewater at a highway rest stop and visitor center in Vermont. The concentrations of detected PPCPs were substantially greater than values reported for conventional WWTPs likely due to onsite recirculation of wastewater. The greatest reductions in PPCPs concentrations were observed in the anoxic treatment tank where Bacilli dominated the biofilm community. Benzoate degradation was the most abundant xenobiotic metabolic category identified throughout the system. Collectively, the microbial communities residing in the wastewater were taxonomically and metabolically more diverse than the immersed plant root biofilm. However, greater heterogeneity and higher relative abundances of xenobiotic metabolism genes was observed for the root biofilm. PMID:27610223

  12. Generic vs custom; analogue vs digital: on the implementation of an online EEG signal processing algorithm.

    Science.gov (United States)

    Casson, Alexander J; Rodriguez-Villegas, Esther

    2008-01-01

    This paper quantifies the performance difference between custom and generic hardware algorithm implementations, illustrating the challenges that are involved in Body Area Network signal processing implementations. The potential use of analogue signal processing to improve the power performance is also demonstrated.

  13. Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L

    DEFF Research Database (Denmark)

    Parker, Erica N; Song, Jiangli; Kishore Kumar, G D;

    2015-01-01

    selective in their inhibition of cathepsin L compared to cathepsin B. Thiosemicarbazone analogue 32 inhibited invasion through Matrigel of MDA-MB-231 breast cancer cells by 70% at 10μM. Thiosemicarbazone analogue 8 significantly inhibited the invasive potential of PC-3ML prostate cancer cells by 92% at 5μ......) was well-tolerated in a CDF1 mouse model bearing an implanted C3H mammary carcinoma, and showed efficacy in tumor growth delay. Low cytotoxicity, inhibition of cell invasion, and in vivo tolerability are desirable characteristics for anti-metastatic agents functioning through an inhibition of cathepsin L...

  14. Fluxon analogues and dark solitons in linearly coupled Bose-Einstein comdensates

    CERN Document Server

    Qadir, Muhammad I; Matthews, Paul C

    2011-01-01

    Two effectively one-dimensional parallel coupled Bose-Einstein condensates in the presence of external potentials are studied. The system is modelled by linearly coupled Gross-Pitaevskii equations. In particular, grey-soliton-like solutions representing analogues of superconducting Josephson fluxons as well as coupled dark solitons are discussed. Theoretical approximations based on variational formulations are derived. It is found that the presence of a magnetic trap can destabilize the fluxon analogues. However, stabilization is possible by controlling the effective linear coupling between the condensates.

  15. Tetrahydrofuran amino acid-containing gramicidin S analogues with improved biological profiles.

    Science.gov (United States)

    Pal, Sudip; Singh, Gajendra; Singh, Shyam; Tripathi, Jitendra Kumar; Ghosh, Jimut Kanti; Sinha, Sudhir; Ampapathi, Ravi Sankar; Chakraborty, Tushar Kanti

    2015-06-28

    Gramicidin S (GS) is a cyclic cationic antimicrobial peptide (CAP) with a wide spectrum of antibiotic activities whose usage has been limited to topical applications owing to its cytotoxic side effects. We have synthesized tetrahydrofuran amino acid (Taa)-containing GS analogues, and we have carried out conformational analysis and explored their structure activity relationships by evaluating their antitubercular, antibacterial and cytotoxic properties. Two of these analogues showed impressive as well as selective activity against Mycobacterium tuberculosis (MTB) without toxicity towards mammalian Vero cells or human RBCs, and are promising as potential leads. PMID:26008215

  16. Potential effect of some environmental factors on the phage removal during wastewater treatment. Study in vitro

    International Nuclear Information System (INIS)

    Great quantities of enteric viruses and bacteriophages are included in wastewaters. They represent a contamination risk of natural water systems. But this viral burden is greatly reduced in the sewage treatment plants by the combined action of numerous environmental factors. To study water quality, some groups of bacteriophages as E. coli phages and Bacteroides fragilis phages have been proposed as model viruses. On an other hand, somatic and, in particular, F-specific coliphages have several morphological, structural and chemical composition ressemblances with the enteric viruses. Two different bacteriophages (øX-174 and MS2) were used as virus models in this in vitro study to evaluate the viral adsorption on suspended clay particles. Distilled sterile water was used as reactional medium to avoid the possible interactions with the considered substrates, the kaolinite (K) and the montmorillonite (M). Phage behaviour in the water and in the recommended diluent for phages, the saline peptone, was first compared. K and M suspensions were used at 300 mg/l for a contact time of 5, 30 and 60 min. In other series K and M suspensions were prepared at 600, 300 and 100 mg/l then used to determine the phage adsorption capacity in a fixed time 30 min. Results show that the phage titers for all samples were constant in the organic diluent. They were lower in the distilled sterile water and decrease with the time. Distilled water favours most likely the grouping of virions and leads aggregates formation. The adsorption of øX-174 and MS2 onto K or M particles was instantaneous and independent of the duration contact. The clay concentration had a slight significant influence on the phage adsorption rate. Using the same phages we have studied, in a second stage, the potential effect of the dissolved matters in a filtered polluted effluent, that of sunlight radiations and that of the protozoan Tetrahymena pyriformis on the phage removal. No soon significant phage inactivation was

  17. Identification of potential toxicity caused by O3 and ClO2 treatment of pharmaceuticals in wastewater

    DEFF Research Database (Denmark)

    Furuhagen, S. M.; Hörsing, Maritha; Ledin, Anna;

    2011-01-01

    Chemical oxidation treatment is an effective innovative technology in wastewater treatment plants for removal of micro-pollutants in the effluent. In particular, ozonation (O3) and chlorine dioxide (ClO2) treatments are commonly used to degrade organic pollutants. By oxidation, the micro-pollutan......Chemical oxidation treatment is an effective innovative technology in wastewater treatment plants for removal of micro-pollutants in the effluent. In particular, ozonation (O3) and chlorine dioxide (ClO2) treatments are commonly used to degrade organic pollutants. By oxidation, the micro......-pollutants are generally transformed to compounds that are easier to degrade biologically. There is, however, a risk that the transformation products will have structures similar to the parent compound and still be biologically active. It has been shown, for example, that transformation products generated from...... Carbamazepine by chemical oxidation were more harmful to aquatic organisms compared to the parent compound. The aim of our study is to evaluate the potential risk of oxidation treatment, using O3 and ClO2, due to formation of toxic transformation products. The ecotoxicological effects caused by the two...

  18. Event-related potentials reflect the efficacy of pharmaceutical treatments in children and adolescents with attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Yamamuro, Kazuhiko; Ota, Toyosaku; Iida, Junzo; Nakanishi, Yoko; Matsuura, Hiroki; Uratani, Mitsuhiro; Okazaki, Kosuke; Kishimoto, Naoko; Tanaka, Shohei; Kishimoto, Toshifumi

    2016-08-30

    Few objective biological measures of pharmacological treatment efficacy exist for attention deficit/hyperactivity disorder (ADHD). Although we have previously demonstrated that event-related potentials (ERPs) reflect the effects of osmotic-release methylphenidate in treatment of naïve pediatric patients with ADHD, whether this is true for the therapeutic effects of atomoxetine (ATX) is unknown. Here, we used the Japanese version of the ADHD rating-scale IV to evaluate 14 patients with ADHD, and compared their ERP data with 14 age- and sex-matched controls. We measured P300 and mismatch negativity (MMN) components during an auditory oddball task before treatment (treatment naïve) and after 2 months of ATX treatment. Compared with controls, P300 components at baseline were attenuated and prolonged in the ADHD group at Fz (fronto-central), Cz (centro-parietal), Pz (parietal regions), C3 and C4 electrodes. ATX treatment reduced ADHD symptomology, and after 2 months of treatment, P300 latencies at Fz, Cz, Pz, C3, and C4 electrodes were significantly shorter than those at baseline. Moreover, MMN amplitudes at Cz and C3 electrodes were significantly greater than those at baseline. Thus, ERPs may be useful for evaluating the pharmacological effects of ATX in pediatric and adolescent patients with ADHD. PMID:27318633

  19. Model Membrane and Cell Studies of Antimicrobial Activity of Melittin Analogues.

    Science.gov (United States)

    Jamasbi, Elaheh; Mularski, Anna; Separovic, Frances

    2016-01-01

    Melittin is a 26 residue peptide and the major component of bee (Apis mellifera) venom. Although melittin has both anticancer and antimicrobial properties, utilization has been limited due to its high lytic activity against eukaryotic cells. The mechanism of this lytic activity remains unclear but several mechanisms have been proposed, including pore formation or a detergent like mechanism, which result in lysis of cell membranes. Several analogues of melittin have been synthesized to further understand the role of specific residues in its antimicrobial and lytic activity. Melittin analogues that have a proline residue substituted for an alanine, lysine or cysteine have been studied with both model membrane systems and living cells. These studies have revealed that the proline residue plays a critical role in antimicrobial activity and cytotoxicity. Analogues lacking the proline residue and dimers of these analogues displayed decreased cytotoxicity and minimum inhibition concentrations. Several mutant studies have shown that, when key substitutions are made, the resultant peptides have more activity in terms of pore formation than the native melittin. Designing analogues that retain antimicrobial and anticancer activity while minimizing haemolytic activity will be a promising way to utilize melittin as a potential therapeutic agent. PMID:26139117

  20. Accumulation of radium in relation to some chemical analogues in Dicranopteris linearis

    Energy Technology Data Exchange (ETDEWEB)

    Chao, J.H., E-mail: jhchao@mx.nthu.edu.t [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chuang, C.Y. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan (China)

    2011-01-15

    This study elucidates the uptake and accumulation of radium in the field-growing fern Dicranopteris linearis by relating the radium concentration to some potential chemical analogues, including alkaline earth metals, rare earth elements, and some important heavy metals. Time-dependent accumulation of radium and these chemical analogues for D. linearis were described by the {sup 228}Th/{sup 228}Ra activity ratio, an index for inferring plant age. The correlation between radium and these elements was assessed by statistical analysis and used as a reference to elucidate the uptake and accumulation of radium in relation to the chemical analogues. Analytical and statistical results showed that the concentrations of alkaline earth metals (except for Mg) rare earth elements and some heavy metals in D. linearis increased linearly with plant age. These elements, exhibiting a similar accumulation pattern to radium and significant correlation coefficients with radium, were considered as the chemical analogues to radium. Additionally, the plant/soil concentration ratios (CRs) for radium and most of these analogues in D. linearis exceeded 1, consistent with the definition of hyper-accumulator plants.