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Sample records for drugs modify casein-induced

  1. The disease modifying osteoarthritis drug (DMOAD)

    DEFF Research Database (Denmark)

    Qvist, Per; Bay-Jensen, Anne-Christine; Christiansen, Claus

    2008-01-01

    Till date, the pharmaceutical industry has failed to bring effective and safe disease modifying osteoarthritic drugs (DMOADs) to the millions of patients suffering from this serious and deliberating disease. We provide a review of recent data reported on the investigation of DMOADs in clinical tr...

  2. Disease-modifying drugs in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ghezzi L

    2013-12-01

    Full Text Available Laura Ghezzi, Elio Scarpini, Daniela Galimberti Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy Abstract: Alzheimer's disease (AD is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition. Keywords: Alzheimer's disease, acetylcholinesterase inhibitors, memantine, disease-modifying drugs, diagnosis, treatment

  3. Oral administration of D-003, a mixture of very long chain fatty acids prevents casein-induced endogenous hypercholesterolemia in rabbits.

    Science.gov (United States)

    Menéndez, R; Más, R; Pérez, J; González, R M; Jiménez, S

    2004-01-01

    D-003 is a mixture of very long chain saturated fatty acids (VLCSFA) purified from sugar cane wax with cholesterol-lowering effects proven in animal models and healthy volunteers. D-003 inhibits cholesterol biosynthesis through the regulation of HMG-CoA reductase activity. Rabbits fed diets enriched with casein develop endogenous hypercholesterolemia (EH), making them a very useful model for determining the mechanism of action of drugs affecting lipids. We examined whether D-003 prevented EH. Rabbits were fed a casein diet for 4 weeks, administered simultaneously with D-003 (5, 50, and 100 mg.kg-1.day-1). As expected, nontreated rabbits became hypercholesterolemic; however, as early as 15 days following administration, the treated group (50 and 100 mg.kg-1.day-1) had significantly decreased total cholesterol and low-density lipoprotein cholesterol (LDL-C). Triglycerides were not affected; however, at study completion, HDL-C levels significantly increased at all the doses assayed. D-003 inhibited de novo synthesis of cholesterol, since the incorporation of 3H2O into sterols in the liver and proximal small bowel was significantly depressed. Also, D-003 significantly raised the rate of removal of [125I]-LDL from serum and significantly elevated [125I]-LDL binding activity to liver homogenates. Taken together, these results show that the efficacy of D-003 in reducing casein-derived hypercholesterolemia could involve, at least partially, an inhibition of hepatic cholesterol biosynthesis, which may elicit a decreased cholesterol concentration in hepatocytes, preventing the loss of hepatic LDL receptors induced by casein administration. However, since casein-induced hypercholesterolemia is also a consequence of a stimulation of cholesterol absorption in the lumen and an increase of the output of cholesterol associated with LDL, the effect of D-003 on cholesterol absorption and LDL synthesis by the liver should be investigated.

  4. Surface-modified nanocrystalline ceramics for drug delivery applications.

    Science.gov (United States)

    Kossovsky, N; Gelman, A; Sponsler, E E; Hnatyszyn, H J; Rajguru, S; Torres, M; Pham, M; Crowder, J; Zemanovich, J; Chung, A

    1994-12-01

    Drug delivery systems comprised of various types of carriers have long been the object of pharmacological investigation. The search has been stimulated by the belief that carriers will lead to reduced drug toxicity, dosage requirements, enhanced cellular targeting and improved shelf-life. Among the carriers investigated are complex polymeric carbohydrates, synthetic proteins and liposomal structures. For the past four years, we have been experimenting with a radically new class of carriers comprised of surface-modified nanocrystalline ceramics. While the ceramics provide the structural stability of a largely immutable solid, the surface modification creates a glassy molecular stabilization film to which pharmacological agents may be bound non-covalently from an aqueous phase with minimal structural denaturation. As a consequence of maintained structural integrity and owing to concentration effects afforded by the surfaces of the nanocrystalline materials, drug activity following surface immobilization is preserved. We have used successfully surface-modified nanocrystalline ceramics to deliver viral antigens for the purpose of evoking an immune response, oxygenated haemoglobin for cell respiration and insulin for carbohydrate metabolism. The theoretical principles, technical details and experimental results are reviewed. Surface-modified nanocrystalline materials offer an exciting new approach to the well-recognized challenges of drug delivery.

  5. Gelatin modified lipid nanoparticles for anti- viral drug delivery.

    Science.gov (United States)

    K S, Joshy; S, Snigdha; Kalarikkal, Nandakumar; Pothen, Laly A; Thomas, Sabu

    2017-10-01

    The major challenges to clinical application of zidovudine are its moderate aqueous solubility and relative short half-life and serious side effects due to frequent administrations. We investigated the preparation of zidovudine-loaded nanoparticles based on lipids which were further modified with the polymer gelatin. Formulation and stability of the modified nanoparticles were analysed from the physico-chemical characterizations. The interactions of nanoparticles with blood components were tested by haemolysis and aggregation studies. The drug content and entrapment efficiencies were assessed by UV analysis. The effect of nanoparticles on protein adsorption was assessed by native polyacrylamide gel electrophoresis (PAGE). In vitro release studies showed a sustained release profile of zidovudine. In vitro cytotoxicity and cellular uptake of the zidovudine-loaded nanoparticles were performed in MCF-7 and neuro 2a brain cells. The enhanced cellular internalization of drug loaded modified nanoparticles in both the cell lines were revealed by fluorescence microscopy. Hence the present study focuses on the feasibility of zidovudine-loaded polymer modified lipid nanoparticles as carriers for safe and efficient HIV/AIDS therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Modified drug release using atmospheric pressure plasma deposited siloxane coatings

    International Nuclear Information System (INIS)

    Dowling, D P; Law, V J; Ardhaoui, M; Stallard, C; Maher, S; Keenan, A

    2016-01-01

    This pilot study evaluates the potential of atmospheric plasma polymerised coatings to modify the rate of drug release from polymeric substrates. The antibiotic rifampicin was deposited in a prototype multi-layer drug delivery system, consisting of a nebulized layer of active drug between a base layer of TEOS deposited on a plastic substrate (polystyrene) and an overlying layer of plasma polymerised PDMS. The polymerised TEOS and PDMS layers were deposited using a helium atmospheric plasma jet system. Elution of rifampicin was measured using UV–VIS spectroscopy, in addition to a antimicrobial well diffusion assay with an established indicator organism. The multi-layered plasma deposited coatings significantly extended the duration of release of the rifampicin from 24 h for the uncoated polymer to 144 h for the coated polymer. (paper)

  7. The modified nanocrystalline cellulose for hydrophobic drug delivery

    International Nuclear Information System (INIS)

    Qing, Weixia; Wang, Yong; Wang, Youyou; Zhao, Dongbao; Liu, Xiuhua; Zhu, Jinhua

    2016-01-01

    Graphical abstract: - Highlights: • Torispherical NCC was synthesized through the improvements on the hydrolysis method. • NCC was firstly modified with CTMAB as a drug carrier. • Luteolin and luteoloside loading CTMAB-coated NCC were studied. - Abstract: In this work, torispherical nanocrystalline cellulose (NCC) was synthesized, and firstly modified with a cationic surfactant cetyltrimethylammonium bromide (CTMAB). It was proved that the kinetics of NCC adsorbing CTMAB followed the pseudo-second-order kinetics equation, and the adsorption isotherm model followed Freundlich which was multi molecular layer adsorption model. The morphology and structure of NCC and CTMAB-coated NCC were characterized by transmission electron microscopy (TEM) and X-ray powder diffraction (XRD). Stabilities of NCC and CTMAB-coated NCC were assayed by zeta potential. The results showed that NCC in CTMAB solution was well-dispersed and stable. Moreover, the drug loading and release performance of CTMAB-coated NCC were studied using luteolin (LUT) and luteoloside (LUS) as model drugs.

  8. Chitosan nanoparticles as a modified diclofenac drug release system

    Science.gov (United States)

    Duarte Junior, Anivaldo Pereira; Tavares, Eraldo José Madureira; Alves, Taís Vanessa Gabbay; de Moura, Márcia Regina; da Costa, Carlos Emmerson Ferreira; Silva Júnior, José Otávio Carréra; Ribeiro Costa, Roseane Maria

    2017-08-01

    This study evaluated a modified nanostructured release system employing diclofenac as a drug model. Biodegradable chitosan nanoparticles were prepared with chitosan concentrations between 0.5 and 0.8% ( w/ v) by template polymerization method using methacrylic acid in aqueous solution. Chitosan-poly(methacrylic acid) (CS-PMAA) nanoparticles showed uniform size around 50-100 nm, homogeneous morphology, and spherical shape. Raw material and chitosan nanoparticles were characterized by thermal analysis, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM), confirming the interaction between chitosan and methacrylic acid during nanoparticles preparation. Diclofenac sorption on the chitosan nanoparticles surface was achieved by incubation in water/ethanol (1:1) drug solution in concentrations of 0.5 and 0.8 mg/mL. The diclofenac amount sorbed per gram of CS-PMAA nanoparticles, when in a 0.5 mg/mL sodium diclofenac solution, was as follows: 12.93, 15, 20.87, and 29.63 mg/g for CS-PMAA nanoparticles 0.5, 0.6, 0.7, and 0.8% ( w/ v), respectively. When a 0.8 mg/mL sodium diclofenac solution was used, higher sorption efficiencies were obtained: For CS-PMAA nanoparticles with chitosan concentrations of 0.5, 0.6, 0.7, and 0.8% ( w/ v), the sorption efficiencies were 33.39, 49.58, 55.23, and 67.2 mg/g, respectively. Diclofenac sorption kinetics followed a second-order kinetics. Drug release from nanoparticles occurred in a period of up to 48 h and obeyed Korsmeyer-Peppas model, which was characterized mainly by Fickian diffusion transport. [Figure not available: see fulltext.

  9. Scleroglucan: A Versatile Polysaccharide for Modified Drug Delivery

    Directory of Open Access Journals (Sweden)

    Franco Alhaique

    2005-01-01

    Full Text Available Scleroglucan is a natural polysaccharide, produced by fungi of the genus Sclerotium, that has been extensively studied for various commercial applications (secondary oil recovery, ceramic glazes, food, paints, etc. and also shows several interesting pharmacological properties. This review focuses its attention on the use of scleroglucan, and some derivatives, in the field of pharmaceutics and in particular for the formulation of modified-release dosage forms. The reported investigations refer mainly to the following topics: natural scleroglucan suitable for the preparation of sustained release tablets and ocular formulations; oxidized and crosslinked scleroglucan used as a matrix for dosage forms sensitive to environmental conditions; co-crosslinked scleroglucan/gellan whose delivery rate can be affected by calcium ions. Furthermore, a novel hydrogel obtained with this polysaccharide and borate ions is described, and the particular structure of this hydrogel network has been interpreted in terms of conformational analysis and molecular dynamics. Profound attention is devoted to the mechanisms involved in drug release from the tested dosage forms that depend, according to the specific preparation, on swelling and/or diffusion. Experimental data are also discussed on the basis of a mathematical approach that allows a better understanding of the behavior of the tested polymeric materials.

  10. Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Taroumian, Sara; Knowles, Susan L; Lisse, Jeffrey R; Yanes, James; Ampel, Neil M; Vaz, Austin; Galgiani, John N; Hoover, Susan E

    2012-12-01

    Coccidioidomycosis (valley fever) is an endemic fungal infection of the American Southwest, an area with a large population of patients with rheumatic diseases. There are currently no guidelines for management of patients who develop coccidioidomycosis while under treatment with biologic response modifiers (BRMs) or disease-modifying antirheumatic drugs (DMARDs). We conducted a retrospective study of how both concurrent diseases were managed and the patient outcomes at 2 centers in Tucson, Arizona. A retrospective chart review identified patients who developed coccidioidomycosis during treatment with DMARDs or BRMs. Patients were seen at least once in a university-affiliated or Veterans Affairs outpatient rheumatology clinic in Tucson, Arizona, between 2007 and 2009. Forty-four patients were identified. Rheumatologic treatment included a BRM alone (n = 11), a DMARD alone (n = 8), or combination therapy (n = 25). Manifestations of coccidioidomycosis included pulmonary infection (n = 29), disseminated disease (n = 9), and asymptomatic positive coccidioidal serologies (n = 6). After the diagnosis of coccidioidomycosis, 26 patients had BRMs and DMARDs stopped, 8 patients had BRMs stopped but DMARD therapy continued, and 10 patients had no change in their immunosuppressive therapy. Forty-one patients had antifungal therapy initiated for 1 month or longer. Followup data were available for 38 patients. BRM and/or DMARD therapy was continued or resumed in 33 patients, only 16 of whom continued concurrent antifungal therapy. None of the patients have had subsequent dissemination or complications of coccidioidomycosis. Re-treating rheumatic disease patients with a BRM and/or a DMARD after coccidioidomycosis appears to be safe in some patients. We propose a management strategy based on coccidioidomycosis disease activity. Copyright © 2012 by the American College of Rheumatology.

  11. A high-fat, high-protein diet attenuates the negative impact of casein-induced chronic inflammation on testicular steroidogenesis and sperm parameters in adult mice.

    Science.gov (United States)

    Zhao, Jing-Lu; Zhao, Yu-Yun; Zhu, Wei-Jie

    2017-10-01

    RNA and protein levels of the StAR and 3β-HSD in group HFPD+CS were both higher than those of in group ND+CS. These results indicated that Kunming male mice with high-fat, high-protein diet and casein injection for 8weeks can be used to establish a diet-induced obesity and chronic systemic inflammation. The sperm parameters in groups ND+CS and HFPD+SI decreased accompanied by pathological changes of testicular tissue. This resultant effect of reduced serum testosterone levels was associated with the overproduction of TNF-α and IL-10 and down-regulation of StAR and CYP11A1. Under the same casein-induced chronic inflammation condition, the mice with high-fat, high-protein diet had better testicular steroidogenesis activity and sperm parameters compared with the mice in normal diet, indicating that the mice with casein-induced inflammatory injury consuming a high-fat, high-protein diet gained weight normally, reduced serum adiponectin level and increased testosterone production by an upregulation of 3β-HSD expression. High-fat, high-protein diet attenuated the negative impact of casein-induced chronic inflammation on testicular steroidogenesis and sperm parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. RGD-modified lipid disks as drug carriers for tumor targeted drug delivery

    Science.gov (United States)

    Gao, Jie; Xie, Cao; Zhang, Mingfei; Wei, Xiaoli; Yan, Zhiqiang; Ren, Yachao; Ying, Man; Lu, Weiyue

    2016-03-01

    Melittin, the major component of the European bee venom, is a potential anticancer candidate due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, especially when applied through intravenous administration. The polyethylene glycol-stabilized lipid disk is a novel type of nanocarrier, and the rim of lipid disks has a high affinity to amphiphilic peptides. In our study, a c(RGDyK) modified lipid disk was developed as a tumor targeted drug delivery system for melittin. Cryo-TEM was used to confirm the shape and size of lipid disks with or without c(RGDyK) modification. In vitro and in vivo hemolysis analyses revealed that the hemolysis effect significantly decreased after melittin associated with lipid disks. Importantly, the results of our in vivo biodistribution and tumor growth inhibitory experiments showed that c(RGDyK) modification increased the distribution of lipid disks in the tumor and the anticancer efficacy of melittin loaded lipid disks. Thus, we successfully achieved a targeted drug delivery system for melittin and other amphiphilic peptides with a good therapeutic effect and low side effects.

  13. Modified Transdermal Technologies: Breaking the Barriers of Drug ...

    African Journals Online (AJOL)

    Transdermal drug technology specialists are continuing to search for new methods that can effectively and painlessly deliver larger molecules in therapeutic quantities to overcome the difficulties associated with the oral route, namely poor bioavailability due to hepatic metabolism (first pass) and the tendency to produce ...

  14. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

    NARCIS (Netherlands)

    Vroom, Fokaline; de Walle, Hermien E. K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R. B. J.; de Jong-van den Berg, Lolkje T. W.

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD

  15. Cognitive enhancers (Nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. Disease-modifying drugs. Update 2014.

    Science.gov (United States)

    Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

    2014-01-01

    Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers, are very productive. The review "Drugs interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs" was accepted in October 2012. In the last 20 months, new targets for the potential treatment of Alzheimer's disease were identified. Enormous progress was realized in the pharmacological characterization of natural products with cognitive enhancing properties. This review covers the evolution of research in this field through May 2014.

  16. Rosiglitazone attenuates casein-induced hepatic endoplasmic reticulum stress in Sprague-Dawley rats: a novel model of endoplasmic reticulum stress.

    Science.gov (United States)

    Kang, Saet Byol; Kim, Hyun Min; Kim, Hyung Jun; Seok, Hannah; Huh, Ji Hye; Lee, Byung-Wan; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

    2013-01-01

    The proteins found in cow milk have been reported to cause systemic inflammation. Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders including insulin resistance and non-alcoholic fatty liver disease. However, the effect of thiazolidinediones (TZDs) on ER stress is still controversial. This is why we want to investigate in this study whether casein, which is the major protein in cow's milk, induces ER stress in the liver and whether rosiglitazone can attenuate these changes. Nine-week-old male Sprague-Dawley (SD) rats were separated into three groups: (1) vehicle treated; (2) daily subcutaneous injections of 1 mL 10% casein; (3) daily subcutaneous injection of 1 mL 10% casein and rosiglitazone 4 mg/[kg d]. After 6 weeks, body weight, food intake, glucose and lipid parameters, and serum AST/ALT levels were measured after an overnight fast. Real time RT-PCR and immunohistochemical staining for various ER stress markers were performed, and a TUNEL analysis was also performed. After 6 weeks, casein injection induced weight reduction, systemic inflammation, and hepatic dysfunction in SD rats. Casein injection increased both the gene and protein expression of ER stress markers in the liver and also caused hepatocyte apoptosis. Rosiglitazone treatment attenuated casein-induced systemic inflammation, ER stress, deteriorated liver function, and increased apoptosis. In conclusion, our results may provide further insight into the effects of casein on chronic inflammatory diseases, and to have a better understanding of the mechanism of the anti-inflammatory properties of rosiglitazone regardless of its hypoglycemic effect.

  17. Screening for drug and alcohol abuse among older adults using a modified version of the CAGE.

    Science.gov (United States)

    Hinkin, C H; Castellon, S A; Dickson-Fuhrman, E; Daum, G; Jaffe, J; Jarvik, L

    2001-01-01

    This study examined the sensitivity, specificity, and receiver operating characteristics (ROC) curves of a modified version of the CAGE, a screening measure used in the detection of older alcohol- and drug-abusing individuals. In a retrospective review of clinical records of 976 patients screened by a geriatric substance abuse program, the authors examined patients' responses on a modified version of the CAGE that included queries regarding drug use. The CAGE was administered to individuals age 50 or over draw from three diagnostic groups: alcohol abuse/dependence, drug abuse/dependence, and normal controls. Analysis of variance and discriminant function analyses revealed that the modified CAGE was able to discriminate both alcohol and drug abusers from controls. Analyses examining test sensitivity, specificity, and ROC curves revealed the CAGE to demonstrate excellent sensitivity but poor specificity. Omitting the "cut down'' item from the CAGE significantly improved specificity with only a modest drop in sensitivity. Given the ease of administration and sensitivity to both alcohol and drug abuse, these data suggest that the modified CAGE is well suited as a screening instrument for geriatric drug and alcohol abuse.

  18. Hybrid Nanostructures Containing Sulfadiazine Modified Chitosan as Antimicrobial Drug Carriers

    Directory of Open Access Journals (Sweden)

    Bogdanel Silvestru Munteanu

    2016-11-01

    Full Text Available Chitosan (CH nanofibrous structures containing sulfadiazine (SDZ or sulfadiazine modified chitosan (SCH in the form of functional nanoparticles attached to nanofibers (hybrid nanostructures were obtained by mono-axial and coaxial electrospinning. The mono-axial design consisted of a SDZ/CH mixture solution fed through a single nozzle while the coaxial design consisted of SCH and CH solutions separately supplied to the inner and outer nozzle (or in reverse order. The CH ability to form nanofibers assured the formation of a nanofiber mesh, while SDZ and SCH, both in form of suspensions in the electrospun solution, assured the formation of active nanoparticles which remained attached to the CH nanofiber mesh after the electrospinning process. The obtained nanostructures were morphologically characterized by scanning electron microscopy (SEM and atomic force microscopy (AFM. The SDZ release profiles and kinetics were analyzed. The SDZ or SCH nanoparticles loosely attached at the surface of the nanofibers, provide a burst release in the first 20 min, which is important to stop the possible initial infection in a wound, while the SDZ and SCH from the nanoparticles which are better confined (or even encapsulated into the CH nanofibers would be slowly released with the erosion/disruption of the CH nanofiber mesh.

  19. Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

    Science.gov (United States)

    Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P

    2017-12-01

    The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Proposal for a new nomenclature of disease-modifying antirheumatic drugs

    NARCIS (Netherlands)

    Smolen, Josef S.; van der Heijde, Desiree; Machold, Klaus P.; Aletaha, Daniel; Landewe, Robert

    2014-01-01

    In light of the recent emergence of new therapeutics for rheumatoid arthritis, such as kinase inhibitors and biosimilars, a new nomenclature for disease-modifying antirheumatic drugs (DMARDs), which are currently often classified as synthetic (or chemical) DMARDs (sDMARDS) and biological DMARDs

  1. [The trend of developing new disease-modifying drugs in Alzheimer's disease].

    Science.gov (United States)

    Arai, Hiroyuki; Furukawa, Katsutoshi; Tomita, Naoki; Ishiki, Aiko; Okamura, Nobuyuki; Kudo, Yukitsuka

    2016-03-01

    Development of symptomatic treatment of Alzheimer s disease by cholinesterase inhibitors like donepezil was successful. However, it is a disappointment that development of disease-modifying drugs such as anti-amyloid drug based on amyloid-cascade theory has been interrupted or unsuccessful. Therefore, we have to be more cautious regarding inclusion criteria for clinical trials of new drugs. We agree that potentially curative drugs should be started before symptoms begin as a preemptive therapy or prevention trial. The concept of personalized medicine also is important when ApoE4-related amyloid reducing therapy is considered. Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry of Health, Labour and Welfare gave a final remark that there was nothing wrong in the data managing process in the J-ADNI data center. We should pay more attention to worldwide challenges of speeding up new drug development.

  2. Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-10-01

    Full Text Available Chitosan, a natural cationic polysaccharide, is prepared industrially by the hydrolysis of the aminoacetyl groups of chitin, a naturally available marine polymer. Chitosan is a non-toxic, biocompatible and biodegradable polymer and has attracted considerable interest in a wide range of biomedical and pharmaceutical applications including drug delivery, cosmetics, and tissue engineering. The primary hydroxyl and amine groups located on the backbone of chitosan are responsible for the reactivity of the polymer and also act as sites for chemical modification. However, chitosan has certain limitations for use in controlled drug delivery and tissue engineering. These limitations can be overcome by chemical modification. Thus, modified chitosan hydrogels have gained importance in current research on drug delivery and tissue engineering systems. This paper reviews the general properties of chitosan, various methods of modification, and applications of modified chitosan hydrogels.

  3. Cognitive enhancers (nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. disease-modifying drugs.

    Science.gov (United States)

    Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

    2013-01-01

    Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

  4. Development of Drug Loaded Nanoparticles Binding to Hydroxyapatite Based on a Bisphosphonate Modified Nonionic Surfactant

    Directory of Open Access Journals (Sweden)

    Jiabin Zhang

    2015-01-01

    Full Text Available This study aimed at development of drug loaded nanoparticles which could bind to hydroxyapatite (HA to construct drug or growth factor releasing bone graft substitutes. To this end, the terminal hydroxyl group of a nonionic surfactant Brij 78 (polyoxyethylene (20 stearyl ether was first modified with pamidronate (Pa. Using Pa-Brij 78 as both a surfactant and an affinity ligand to HA, three different Pa surface functionalized nanoparticles were prepared, named as solid lipid nanoparticles (Pa-SNPs, nanoemulsions (Pa-NEMs, and PLGA nanoparticles (Pa-PNPs. A model drug curcumin was successfully encapsulated in the three nanoparticles. The sizes of Pa-NEM and Pa-PNP were around 150 nm and the size of Pa-SNP was around 90 nm with polydispersity indexes (PDIs less than 0.20. Drug encapsulation efficiencies of the three nanoparticles were all greater than 85%. Furthermore, the order of binding affinity of the nanoparticles to HA was Pa-PNP>Pa-NEM=Pa-SNP. After lyophilization, the sizes of the three nanoparticles were increased about 0.5–2.0-fold but their binding affinities to HA were almost the same as the fresh prepared nanoparticles. In conclusion, a Pa-modified Brij 78 was synthesized and used for fabrication of a series of drug loaded nanoparticles to construct drug-eluting HA-based bone graft substitutes.

  5. Light-sensitive intelligent drug delivery systems of coumarin-modified mesoporous bioactive glass.

    Science.gov (United States)

    Lin, H-M; Wang, W-K; Hsiung, P-A; Shyu, S-G

    2010-08-01

    Functionalized mesoporous bioactive glasses (MBG) with photoactive coumarin demonstrates photo-responsive dimerization resulting in reversible gate operation. Coumarin-modified MBG was used as a drug delivery carrier to investigate drug storage/release characteristics using phenanthrene as a model drug. Irradiation with UV light (>310 nm) induced photo-dimerization of the coumarin-modified MBG, which led to the pores' closing with cyclobutane dimers and trapping of the guest phenanthrene in the mesopores. However, irradiating the dimerized-coumarin-modified MBG with shorter wavelength UV light (approximately 250 nm) regenerates the coumarin monomer derivative by the photo-cleavage of cyclobutane dimers, such that trapped guest molecules are released from the mesopores. The structural, morphological, textural and optical properties are well characterized by X-ray diffraction, transmission electron microscopy, N(2) adsorption/desorption, and UV-visible spectroscopy. The results reveal that the MBG exhibits the typical ordered characteristics of the hexagonal mesostructure. The system demonstrates great potential in light-sensitive intelligent drug delivery systems and disease therapy fields. Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.

  6. Biomedical Properties Study of Modified Chitosan Nanoparticles for Drug Delivery Systems

    Science.gov (United States)

    Saboktakin, Mohammad Reza

    2013-09-01

    The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized.

  7. Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Caroline Vieira Spessotto

    2016-08-01

    Full Text Available ABSTRACT Objective The treatment of multiple sclerosis (MS with disease-modifying-drugs (DMDs is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

  8. Nanosized sustained-release drug depots fabricated using modified tri-axial electrospinning.

    Science.gov (United States)

    Yang, Guang-Zhi; Li, Jiao-Jiao; Yu, Deng-Guang; He, Mei-Feng; Yang, Jun-He; Williams, Gareth R

    2017-04-15

    Nanoscale drug depots, comprising a drug reservoir surrounded by a carrier membrane, are much sought after in contemporary pharmaceutical research. Using cellulose acetate (CA) as a filament-forming polymeric matrix and ferulic acid (FA) as a model drug, nanoscale drug depots in the form of core-shell fibers were designed and fabricated using a modified tri-axial electrospinning process. This employed a solvent mixture as the outer working fluid, as a result of which a robust and continuous preparation process could be achieved. The fiber-based depots had a linear morphology, smooth surfaces, and an average diameter of 0.62±0.07μm. Electron microscopy data showed them to have clear core-shell structures, with the FA encapsulated inside a CA shell. X-ray diffraction and IR spectroscopy results verified that FA was present in the crystalline physical form. In vitro dissolution tests revealed that the fibers were able to provide close to zero-order release over 36h, with no initial burst release and minimal tailing-off. The release properties of the depot systems were much improved over monolithic CA/FA fibers, which exhibited a significant burst release and also considerable tailing-off at the end of the release experiment. Here we thus demonstrate the concept of using modified tri-axial electrospinning to design and develop new types of heterogeneous nanoscale biomaterials. Nanoscale drug depots with a drug reservoir surrounded by a carrier are highly attractive in biomedicine. A cellulose acetate based drug depot was investigated in detail, starting with the design of the nanostructure, and moving through its fabrication using a modified tri-axial electrospinning process and a series of characterizations. The core-shell fiber-based drug depots can provide a more sustained release profile with no initial burst effect and less tailing-off than equivalent monolithic drug-loaded fibers. The drug release mechanisms are also distinct in the two systems. This proof

  9. ANALYSIS OF DISEASE MODIFYING DRUGS ADMINISTRATION FREGUENCY AND CAUSES OF THEIR WITHDRAWAL IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E V Pavlova

    2000-01-01

    Full Text Available Aim of studdy: To assess the frequency of practical application of different basic drugs in rheumatoid arthritis (RA. Material and methods: Tlxe study was conducted basing of questionner of pts and analysis of ycases by randomized sampling among 103 consequent pts (M:F= 13:90 with reliable RA (ARA, 1987 in rheumatologic department of Clinical Hospital Nol in Ekaterinburg. 74% of pts under study demonstrated systemic manifestations: anemia (in 47 pts, lymphadenopathy (in 34, rheumatoid nodules (in 15, Sjogren s syndrome (in 4, nephropathy (in 4, vascular disturbances including Raynaud s phenomenon, capillarites (by 1 pt. Results: In the course of disease basic therapy was prescribed to 88 out of103 (85.4% pts and one and the same patient could take different basic drugs. Aminochinoline drugs prevailed, after them more frequent were immunodepressants and gold preparations. More rarely pts had sulfasalazin, cuprenil and wobenzym. In general, in 133 out of 184 cases of prescribing basic drugs they were canceled. The reason for cancellation were: prevalently absence of the drug in the pharmaceutical stores (in 48 cases averagely in 8 months of taking the drug; then they insufficient efficacy (44 cases averagely in 1.3 year. In 18 cases pts themselves stopped treatment averagely in 3.5 months of drug taking. Conclusion: In the majority of cases of basic drugs cancellation in RA the cause is their absence in sail especially on free of charge prescription. Cases ofself-cancellation of the drug demonstrate the need of explaining to pts the necessity> of long-term taking disease-modifying drugs.

  10. Magnetic silica hybrids modified with guanidine containing co-polymers for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Timin, Alexander S., E-mail: a_timin@mail.ru [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000 Ivanovo (Russian Federation); RASA Center in Tomsk, Tomsk Polytechnic University, 30, Lenin Avenue, 634500 Tomsk (Russian Federation); Khashirova, Svetlana Yu. [Kabardino-Balkar State University, ul. Chernyshevskogo 173, Nal' chik, 360004 Kabardino-Balkaria (Russian Federation); Rumyantsev, Evgeniy V.; Goncharenko, Alexander A. [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000 Ivanovo (Russian Federation)

    2016-07-01

    Guanidine containing co-polymers grafted onto silica nanoparticles to form core-shell structure were prepared by sol-gel method in the presence of γ-Fe{sub 2}O{sub 3} nanoparticles. The morphological features for uncoated and coated silica particles have been characterized with scanning electron microscopy. The results show that the polymer coated silicas exhibit spherical morphology with rough polymeric surface covered by γ-Fe{sub 2}O{sub 3} nanoparticles. The grafting amount of guanidine containing co-polymers evaluated by thermogravimetric analysis was in the range from 17 to 30%. Then, the drug loading properties and cumulative release of silica hybrids modified with guanidine containing co-polymers were evaluated using molsidomine as a model drug. It was shown that after polymer grafting the loading content of molsidomine could reach up to 3.42 ± 0.21 and 2.34 ± 0.14 mg/g respectively. The maximum drug release of molsidomine is achieved at pH 1.6 (approximately 71–75% release at 37 °C), whereas at pH 7.4 drug release is lower (50.4–59.6% release at 37 °C). These results have an important implication that our magneto-controlled silica hybrids modified with guanidine containing co-polymers are promising as drug carriers with controlled behaviour under influence of magnetic field. - Highlights: • Polymer coated silica hybrids containing γ-Fe{sub 2}O{sub 3} were prepared via sol–gel method. • Polymer grafting influences pH-response and surface properties of final products. • Molsidomine as a model drug was effectively loaded into polymer coated silicas. • The drug loading depends on the nature of grafted polymer and its content.

  11. Nano molar detection of acyclovir, an antiviral drug at nanoclay modified carbon paste electrode

    Directory of Open Access Journals (Sweden)

    Nagaraj P. Shetti

    2017-06-01

    Full Text Available A nano level voltammetric sensing method has been developed for determination of acyclovir (ACV at nano clay modified carbon paste sensor by employing cyclic voltammetry (CV and square wave voltammetry (SWV techniques in pH 5.0. The electro-oxidation current of ACV was enhanced two times greater by the modification of the sensor. The modifier nano clay was characterized by utilizing X-ray diffraction (XRD and scanning electronic microscope (SEM. The influence of parameters like scan rate, pH, accumulation time, amount of the modifier and concentration on the peak current of the drug were studied. The effect of ACV concentration variation was studied using SWV technique and got lowest detection limit compared to the earlier reported techniques. The fabricated sensor was employed for the determination of acyclovir in pharmaceutical and biological samples.

  12. Electrochemical and DFT study of an anticancer and active anthelmintic drug at carbon nanostructured modified electrode

    International Nuclear Information System (INIS)

    Ghalkhani, Masoumeh; Beheshtian, Javad; Salehi, Maryam

    2016-01-01

    The electrochemical response of mebendazole (Meb), an anticancer and effective anthelmintic drug, was investigated using two different carbon nanostructured modified glassy carbon electrodes (GCE). Although, compared to unmodified GCE, both prepared modified electrodes improved the voltammetric response of Meb, the carbon nanotubes (CNTs) modified GCE showed higher sensitivity and stability. Therefore, the CNTs-GCE was chosen as a promising candidate for the further studies. At first, the electrochemical behavior of Meb was studied by cyclic voltammetry and differential pulse and square wave voltammetry. A one step reversible, pH-dependent and adsorption-controlled process was revealed for electro-oxidation of Meb. A possible mechanism for the electrochemical oxidation of Meb was proposed. In addition, electronic structure, adsorption energy, band gap, type of interaction and stable configuration of Meb on the surface of functionalized carbon nanotubes were studied by using density functional theory (DFT). Obtained results revealed that Meb is weakly physisorbed on the CNTs and that the electronic properties of the CNTs are not significantly changed. Notably, CNTs could be considered as a suitable modifier for preparation of the modified electrode for Meb analysis. Then, the experimental parameters affecting the electrochemical response of Meb were optimized. Under optimal conditions, high sensitivity (b(Meb) = dI p,a (Meb) / d[Meb] = 19.65 μA μM −1 ), a low detection limit (LOD (Meb) = 19 nM) and a wide linear dynamic range (0.06–3 μM) was resulted for the voltammetric quantification of Meb. - Highlights: • Electrochemical oxidation mechanism of Meb was investigated. • A carbon nanostructure modified electrode was developed for the determination of Meb. • The modified electrode surface was characterized by SEM and impedance studies. • This study provides an effective chemically modified electrode with satisfactory repeatability and reproducibility

  13. The systems containing clays and clay minerals from modified drug release: a review.

    Science.gov (United States)

    Rodrigues, Luís Alberto de Sousa; Figueiras, Ana; Veiga, Francisco; de Freitas, Rivelilson Mendes; Nunes, Lívio César Cunha; da Silva Filho, Edson Cavalcanti; da Silva Leite, Cleide Maria

    2013-03-01

    Clays are materials commonly used in the pharmaceutical industry, either as ingredients or as active ingredients. It was observed that when they are administered concurrently, they may interact with drugs reducing their absorption. Therefore, such interactions can be used to achieve technological and biopharmaceutical advantages, regarding the control of release. This review summarizes bibliographic (articles) and technological (patents) information on the use of systems containing clays and clay minerals in modified drug delivery. In this area, formulations such natural clay, commercial clay, synthetic clay, composites clay-polymers, nanocomposites clay-polymers, films and hidrogels composites clay-polymers are used to slow/extend or vectorize the release of drugs and consequently they increase their bioavailability. Finally, this review summarizes the fields of technology and biopharmaceutical applications, where clays are applied. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process

    Science.gov (United States)

    2014-01-01

    This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned. PMID:24940180

  15. Electrocatalytic oxidation of some anti-inflammatory drugs on a nickel hydroxide-modified nickel electrode

    Energy Technology Data Exchange (ETDEWEB)

    Hajjizadeh, M. [Department of Chemistry, Faculty of Science, K. N. Toosi University of Technology, P.O. Box 16315-1618, Tehran (Iran, Islamic Republic of); Jabbari, A. [Department of Chemistry, Faculty of Science, K. N. Toosi University of Technology, P.O. Box 16315-1618, Tehran (Iran, Islamic Republic of)], E-mail: jabbari@kntu.ac.ir; Heli, H.; Moosavi-Movahedi, A.A. [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Haghgoo, S. [Center of Quality Control of Drug, Tehran (Iran, Islamic Republic of)

    2007-12-31

    The electrocatalytic oxidation of several anti-inflammatory drugs (mefenamic acid, diclofenac and indomethacin) was investigated on a nickel hydroxide-modified nickel (NHMN) electrode in alkaline solution. This oxidation process and its kinetics were studied using cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy techniques. Voltammetric studies indicated that in the presence of drugs, the anodic peak current of low-valence nickel species increases, followed by a decrease in the corresponding cathodic current. This pattern indicates that drugs were oxidized on the redox mediator immobilized on the electrode surface via an electrocatalytic mechanism. A mechanism based on the electrochemical generation of Ni(III) active sites and their subsequent consumption by drugs was also investigated. The corresponding rate law under the control of charge transfer was developed and kinetic parameters were derived. In this context, the charge-transfer resistance accessible both theoretically and through impedancemetry was used as a criterion. The rate constants of the catalytic oxidation of drugs and the electron-transfer coefficients are reported. A sensitive, simple and time-saving amperometric procedure was developed for the analysis of these drugs in bulk form and for the direct assay of tablets, using the NHMN electrode.

  16. Electrocatalytic oxidation of some anti-inflammatory drugs on a nickel hydroxide-modified nickel electrode

    International Nuclear Information System (INIS)

    Hajjizadeh, M.; Jabbari, A.; Heli, H.; Moosavi-Movahedi, A.A.; Haghgoo, S.

    2007-01-01

    The electrocatalytic oxidation of several anti-inflammatory drugs (mefenamic acid, diclofenac and indomethacin) was investigated on a nickel hydroxide-modified nickel (NHMN) electrode in alkaline solution. This oxidation process and its kinetics were studied using cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy techniques. Voltammetric studies indicated that in the presence of drugs, the anodic peak current of low-valence nickel species increases, followed by a decrease in the corresponding cathodic current. This pattern indicates that drugs were oxidized on the redox mediator immobilized on the electrode surface via an electrocatalytic mechanism. A mechanism based on the electrochemical generation of Ni(III) active sites and their subsequent consumption by drugs was also investigated. The corresponding rate law under the control of charge transfer was developed and kinetic parameters were derived. In this context, the charge-transfer resistance accessible both theoretically and through impedancemetry was used as a criterion. The rate constants of the catalytic oxidation of drugs and the electron-transfer coefficients are reported. A sensitive, simple and time-saving amperometric procedure was developed for the analysis of these drugs in bulk form and for the direct assay of tablets, using the NHMN electrode

  17. Lipid composition has significant effect on targeted drug delivery properties of NGR-modified liposomes.

    Science.gov (United States)

    Chen, Jun; Lin, Aihua; Peng, Pei; Wang, Yong; Gu, Wei; Liu, Yiming

    2016-05-01

    The Asn-Gly-Arg (NGR) motif has previously been demonstrated to specifically bind to CD13, which is selectively overexpressed in tumor vasculature and some tumor cells (e.g. HT1080). It was reported that NGR-modified stealth liposomes (NGR-SL) could be prepared with different lipid composition, such as 1,2-dipalmitoyl-sn-glycero-phosphatidylcholine (DPPC), hydrogenated soy posphatidylcholine (HSPC) and soy posphatidylcholine (SPC). In the present study, NGR-modified liposomes were prepared with DPPC, HSPC, SPC or the mixture of HSPC and SPC. The resultant liposomes with different lipid composition were compared in terms of cell uptake, antitumor efficacy and targeted drug delivery efficiency using HT1080 tumor model. It was found that NGR-SL composed of the mixture of HSPC and SPC was able to improve targeted drug delivery efficiency to tumor producing the most significant antitumor activity. Collectively, the NGR-modified liposomes composed of the mixture of HSPC and SPC are promising carriers for the treatment of tumor. Besides NGR ligand, lipid composition could also significantly affect the targeted delivery efficiency to the tumor.

  18. Triple-Component Drug-Loaded Nanocomposites Prepared Using a Modified Coaxial Electrospinning

    Directory of Open Access Journals (Sweden)

    Wei Qian

    2013-01-01

    Full Text Available Triple-component nanocomposites for improved sustained drug release profiles are successfully fabricated through a modified coaxial electrospinning process, in which only organic solvent N,N-dimethylacetamide was used as sheath fluid. Using polyacrylonitrile (PAN as filament-forming matrix, ibuprofen (IBU as functional ingredient, and polyvinylpyrrolidone (PVP as the additional component, the IBU/PVP/PAN triple-component nanocomposites had uniform structure and an average diameter of 620±120 nm and 650±120 nm when the contents of PVP in the nanofibers were 10.5% and 22.7%, respectively. The optimal sheath-to-core flow rate ratio was 0.11 under a total sheath and core fluid flow rate of 1.0 mL/h. Compared with the IBU/PAN composite nanofibers, the triple-component composites could release 92.1% and 97.8% of the contained IBU, significantly larger than a value of 73.4% from the former. The inclusion of PVP in the IBU/PAN could effectively avoid the entrapment of IBU in the insoluble PAN molecules, facilitating the in vitro release of IBU. The modified coaxial process and the resulted multiple component nanocomposites would provide new way for developing novel drug sustained materials and transdermal drug delivery systems.

  19. Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Gabay, Cem; Riek, Myriam; Hetland, Merete Lund

    2016-01-01

    OBJECTIVES: To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. METHODS: Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were...... change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. RESULTS: Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year...

  20. Vaccines and Disease-Modifying Antirheumatic Drugs: Practical Implications for the Rheumatologist.

    Science.gov (United States)

    Friedman, Marcia A; Winthrop, Kevin L

    2017-02-01

    Patients with rheumatoid arthritis are highly vulnerable to infections because of abnormalities in their immune system, and because of immunosuppressive effects of their medications. Vaccinations in this population are complicated by disease-modifying antirheumatic drugs, which also modulate or suppress the immune system and potentially decrease the immunogenicity and efficacy of the vaccines. We review the available data regarding the impact of rheumatoid arthritis therapy on the immunogenicity of various common vaccines. We also review rheumatoid arthritis-specific vaccination recommendations, live vaccine safety concerns, and current gaps in our understanding of these issues." Published by Elsevier Inc.

  1. Critical appraisal of the guidelines for the management of ankylosing spondylitis: disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Soriano, Enrique R; Clegg, Daniel O; Lisse, Jeffrey R

    2012-05-01

    Surprisingly, little data are available for the use of disease-modifying antirheumatic drugs in ankylosing spondylitis. Sulfasalazine has been the best studied. Efficacy data for individual agents (including pamidronate) and combinations of agents are detailed in this review. Intriguingly, these agents continue to be used with some frequency, even in the absence of efficacy data. To answer these questions, additional systematic studies of these agents in ankylosing spondylitis are needed and will likely need to be done by interested collaborative groups such as SPARTAN.

  2. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    Science.gov (United States)

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  3. Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

    Directory of Open Access Journals (Sweden)

    Xiaojun Tao

    2016-09-01

    Full Text Available To search for nano-drug preparations with high efficiency in tumor treatment, we evaluated the drug-loading capacity and cell-uptake toxicity of three kinds of nanoparticles (NPs. Pullulan was grafted with ethylenediamine and hydrophobic groups to form hydrophobic cholesterol-modified amino-pullulan (CHAP conjugates. Fourier transform infrared spectroscopy and nuclear magnetic resonance were used to identify the CHAP structure and calculate the degree of substitution of the cholesterol group. We compared three types of NPs with close cholesterol hydrophobic properties: CHAP, cholesterol-modified pullulan (CHP, and cholesterol-modified carboxylethylpullulan (CHCP, with the degree of substitution of cholesterol of 2.92%, 3.11%, and 3.46%, respectively. As compared with the two other NPs, CHAP NPs were larger, 263.9 nm, and had a positive surface charge of 7.22 mV by dynamic light-scattering measurement. CHAP NPs showed low drug-loading capacity, 12.3%, and encapsulation efficiency of 70.8%, which depended on NP hydrophobicity and was affected by surface charge. The drug release amounts of all NPs increased in the acid media, with CHAP NPs showing drug-release sensitivity with acid change. Cytotoxicity of HeLa cells was highest with mitoxantrone-loaded CHAP NPs on MTT assay. CHAP NPs may have potential as a high-efficiency drug carrier for tumor treatment.

  4. Prenatal tactile stimulation attenuates drug-induced behavioral sensitization, modifies behavior, and alters brain architecture.

    Science.gov (United States)

    Muhammad, Arif; Kolb, Bryan

    2011-07-11

    Based on the findings of postnatal tactile stimulation (TS), a favorable experience in rats, the present study examined the influence of prenatal TS on juvenile behavior, adult amphetamine (AMPH) sensitization, and structural alteration in the prefrontal cortex (PFC) and the striatum. Female rats received TS through a baby hair brush throughout pregnancy, and the pups born were tested for open field locomotion, elevated plus maze (EPM), novel object recognition (NOR), and play fighting behaviors. Development and persistence of drug-induced behavioral sensitization in adults were tested by repeated AMPH administration and a challenge, respectively. Structural plasticity in the brain was assessed from the prefrontal cortical thickness and striatum size from serial coronal sections. The results indicate that TS females showed enhanced exploration in the open field. TS decreased the frequency of playful attacks whereas the response to face or evade an attack was not affected. Anxiety-like behavior and cognitive performance were not influenced by TS. AMPH administration resulted in gradual increase in locomotor activity (i.e., behavioral sensitization) that persisted at least for 2 weeks. However, both male and female TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Furthermore, the drug-associated alteration in the prefrontal cortical thickness and striatum size observed in controls were prevented by TS experience. In summary, TS during prenatal development modified juvenile behavior, attenuated drug-induced behavioral sensitization in adulthood, and reorganized brain regions implicated in drug addiction. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Electrochemical and DFT study of an anticancer and active anthelmintic drug at carbon nanostructured modified electrode.

    Science.gov (United States)

    Ghalkhani, Masoumeh; Beheshtian, Javad; Salehi, Maryam

    2016-12-01

    The electrochemical response of mebendazole (Meb), an anticancer and effective anthelmintic drug, was investigated using two different carbon nanostructured modified glassy carbon electrodes (GCE). Although, compared to unmodified GCE, both prepared modified electrodes improved the voltammetric response of Meb, the carbon nanotubes (CNTs) modified GCE showed higher sensitivity and stability. Therefore, the CNTs-GCE was chosen as a promising candidate for the further studies. At first, the electrochemical behavior of Meb was studied by cyclic voltammetry and differential pulse and square wave voltammetry. A one step reversible, pH-dependent and adsorption-controlled process was revealed for electro-oxidation of Meb. A possible mechanism for the electrochemical oxidation of Meb was proposed. In addition, electronic structure, adsorption energy, band gap, type of interaction and stable configuration of Meb on the surface of functionalized carbon nanotubes were studied by using density functional theory (DFT). Obtained results revealed that Meb is weakly physisorbed on the CNTs and that the electronic properties of the CNTs are not significantly changed. Notably, CNTs could be considered as a suitable modifier for preparation of the modified electrode for Meb analysis. Then, the experimental parameters affecting the electrochemical response of Meb were optimized. Under optimal conditions, high sensitivity (b(Meb)=dIp,a(Meb)/d[Meb]=19.65μAμM(-1)), a low detection limit (LOD (Meb)=19nM) and a wide linear dynamic range (0.06-3μM) was resulted for the voltammetric quantification of Meb. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Hydrophobically modified polysaccharide-based on polysialic acid nanoparticles as carriers for anticancer drugs.

    Science.gov (United States)

    Jung, Bom; Shim, Man-Kyu; Park, Min-Ju; Jang, Eun Hyang; Yoon, Hong Yeol; Kim, Kwangmeyung; Kim, Jong-Ho

    2017-03-30

    This study presented the development of hydrophobically modified polysialic acid (HPSA) nanoparticles, a novel anticancer drug nanocarrier that increases therapeutic efficacy without causing nonspecific toxicity towards normal cells. HPSA nanoparticles were prepared by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling between N-deacetylated polysialic acid (PSA) and 5β-cholanic acid. The physicochemical characteristics of HPSA nanoparticles (zeta-potential, morphology and size) were measured, and in vitro cytotoxicity and cellular uptake of PSA and HPSA nanoparticles were tested in A549 cells. In vivo cancer targeting of HPSA nanoparticles was evaluated by labeling PSA and HPSA nanoparticles with Cy5.5, a near-infrared fluorescent dye, for imaging. HPSA nanoparticles showed improved cancer-targeting ability compared with PSA. Doxorubicin-loaded HPSA (DOX-HPSA) nanoparticles were prepared using a simple dialysis method. An analysis of the in vitro drug-release profile and drug-delivery behavior showed that DOX was effectively released from DOX-HPSA nanoparticles. In vivo cancer therapy with DOX-HPSA nanoparticles in mice showed antitumor effects that resembled those of free DOX. Moreover, DOX-HPSA nanoparticles had low toxicity toward other organs, reflecting their tumor-targeting property. Hence, HPSA nanoparticles are considered a potential nanocarrier for anticancer agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A New Strategy for Deleting Animal drugs from Traditional Chinese Medicines based on Modified Yimusake Formula.

    Science.gov (United States)

    Wang, Jinghui; Li, Yan; Yang, Yinfeng; Chen, Xuetong; Du, Jian; Zheng, Qiusheng; Liang, Zongsuo; Wang, Yonghua

    2017-05-04

    Traditional Chinese medicine (TCM), such as Uyghur Medicine (UM) has been used in clinical treatment for many years. TCM is featured as multiple targets and complex mechanisms of action, which is normally a combination of medicinal herbs and sometimes even contains certain rare animal medicinal ingredients. A question arises as to whether these animal materials can be removed replaced from TCM applications due to their valuable rare resources or animal ethics. Here, we select a classical UM Yimusake formula, which contains 3 animal drugs and other 8 herbs, and has got wealthy experience and remarkable achievements in treating erectile dysfunction (ED) in China. The active components, drug targets and therapeutic mechanisms have been comprehensively analyzed by systems-pharmacology methods. Additionally, to validate the inhibitory effects of all candidate compounds on their related targets, in vitro experiments, computational analysis and molecular dynamics simulations were performed. The results show that the modified, original and three animal materials display very similar mechanisms for an effective treatment of ED, indicating that it is quite possible to remove these three animal drugs from the original formula while still keep its efficiency. This work provides a new attempt for deleting animal materials from TCM, which should be important for optimization of traditional medicines.

  8. Preparation and Characterization of Modified Polyethyleneimine Magnetic Nanoparticles for Cancer Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sedighe Arabi

    2016-01-01

    Full Text Available Magnetic nanoparticles with polymeric coating have great significance in drug delivery purpose. We intended to prepare a modified amphiphilic polymer with targeting susceptibility to reduce side effects to normal cells. In this study polyethyleneimine (PEI as a polycationic polymer reacted with sebacoyl chloride to make a new amphiphilic polymer and folic acid as a targeting agent to reduce cytotoxicity of polymer and increase specific entrance of nanoparticles to cancerous cells. The obtained polymer (PEI-Sb-FA was then coated on magnetic nanoparticles (MNPs to stabilize them. The core-shell nanoparticles were characterized by different methods such as scanning electron microscopy (SEM, X-ray diffraction (XRD, thermogravimetric analysis (TGA, and vibrating sample magnetometer (VSM. Curcumin was finally loaded on PEI-Sb-FA-MNPs and the release behavior was studied in different pH. Curcumin loading of 28.2% was obtained and released drug in acidic pH = 4.5 was more than pH = 7.4, showing drug release sensitivity toward pH of media.

  9. Adherence to Disease Modifying Drugs among Patients with Multiple Sclerosis in Germany: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Kerstin Hansen

    Full Text Available Long-term therapies such as disease modifying therapy for Multiple Sclerosis (MS demand high levels of medication adherence in order to reach acceptable outcomes. The objective of this study was to describe adherence to four disease modifying drugs (DMDs among statutorily insured patients within two years following treatment initiation. These drugs were interferon beta-1a i.m. (Avonex, interferon beta-1a s.c. (Rebif, interferon beta-1b s.c. (Betaferon and glatiramer acetate s.c. (Copaxone.This retrospective cohort study used pharmacy claims data from the data warehouse of the German Institute for Drug Use Evaluation (DAPI from 2001 through 2009. New or renewed DMD prescriptions in the years 2002 to 2006 were identified and adherence was estimated during 730 days of follow-up by analyzing the medication possession ratio (MPR as proxy for compliance and persistence defined as number of days from initiation of DMD therapy until discontinuation or interruption.A total of 52,516 medication profiles or therapy cycles (11,891 Avonex, 14,060 Betaferon, 12,353 Copaxone and 14,212 Rebif from 50,057 patients were included into the analysis. Among the 4 cohorts, no clinically relevant differences were found in available covariates. The Medication Possession Ratio (MPR measured overall compliance, which was 39.9% with a threshold MPR≥0.8. There were small differences in the proportion of therapy cycles during which a patient was compliant for the following medications: Avonex (42.8%, Betaferon (40.6%, Rebif (39.2%, and Copaxone (37%. Overall persistence was 32.3% at the end of the 24 months observation period, i.e. during only one third of all included therapy cycles patients did not discontinue or interrupt DMD therapy. There were also small differences in the proportion of therapy cycles during which a patient was persistent as follows: Avonex (34.2%, Betaferon (33.4%, Rebif (31.7% and Copaxone (29.8%.Two years after initiating MS-modifying therapy, only

  10. Electrochemically controlled release of anticancer drug methotrexate using nanostructured polypyrrole modified with cetylpyridinium: Release kinetics investigation

    International Nuclear Information System (INIS)

    Alizadeh, Naader; Shamaeli, Ehsan

    2014-01-01

    A new simple strategy for direct electrochemical incorporation of chemotherapeutic methotrexate (MTX) into conductive polypyrrole (PPy) has been suggested for an electrochemically controlled loading and release system. Electropolymerization of MTX doped polypyrrole yielded poor quality with low efficiency of doping, but a well-doped, nanostructure and increased capacity of drug loading (24.5 mg g −1 ) has been obtained in the presence of cetylpyridinium (CP) as a modifier. When CP was preloaded onto PPy, the hydrophobic surface of the PPy serves as a backbone to which the hydrophobic chain of the CP can be attached. Electrostatic interaction between cationic CP with anionic MTX and aromatic interaction between pyridinium head of CP with pyrimidine and pyrazine rings of MTX increases drug doping. Then release kinetics were investigated at various applied potentials and temperatures. Kinetics analysis based on Avrami's equation showed that the drug release was controlled and accelerated by increasing temperature and negative potential and sustained by increasing positive potential. At open circuit condition, the release parameter (n) represented a diffusive mechanism and at applying electrochemical potentials, a first-order mode. Activation energy parameters (E a , ΔG ≠ , ΔH ≠ and ΔS ≠ ) and half-life time (t 1/2 ) of drug release are also analyzed as a function of applied potential. The nanostructured polymer films (PPy/CP/MTX) were characterized by several techniques: scanning electron microscopy, Furrier transforms Infrared, UV-vis spectroscopy. Overall, our results demonstrate that the PPy/CP/MTX films, combined with electrical stimulation, permit a programmable release of MTX by altering the interaction strength between the PPy/CP and MTX

  11. Low-dose corticosteroids and disease modifying drugs in patients with rheumatoid arthritis.

    Science.gov (United States)

    Malysheva, O; Baerwald, C G

    2011-01-01

    Low-dose glucocorticoids (GCs) exhibit a differential effect on continuation of disease-modifying anti-rheumatic drugs (DMARDs), and the degree of adverse effects (AE) associated with DMARDs. Therefore, GCs address important problems in DMARD use in rheumatoid arthritis (RA), i.e. cumulative toxicity and frequent AE. Low-dose GCs often are recommended to achieve a better symptomatic control or as 'bridge therapy' before the onset of action of DMARDs. RA patients with GC co-medication had better radiographic outcomes but experienced more GC-related AE. Further long-term studies are needed to focus on timing of administration, duration and identification of risk factors for developing AE to establish the optimal use of GCs in the treatment of RA.

  12. Modifying release characteristics from 3D printed drug-eluting products

    DEFF Research Database (Denmark)

    Boetker, Johan; Water, Jorrit; Aho, Johanna

    2016-01-01

    Abstract This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing...... nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10 mm, h = 2 mm). Thermal analysis with differential scanning calorimetry and solid phase...... identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present...

  13. Huperzine A: is it an effective disease-modifying drug for Alzheimer’s disease?

    Directory of Open Access Journals (Sweden)

    Zhong Ming eQian

    2014-08-01

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disorder for which there is no cure. Huperzine A (HupA is a natural inhibitor of acetylcholinesterase (AChE derived from the Chinese folk medicine Huperzia serrata (Qian Ceng Ta. It is a licensed anti-AD drug in China and is available as a nutraceutical in the US. A growing body of evidence has demonstrated that HupA has multifaceted pharmacological effects. In addition to the symptomatic, cognitive-enhancing effect via inhibition of AChE, a number of recent studies have reported that this drug has non-cholinergic effects on AD. Most important among these is the protective effect of HupA on neurons against amyloid beta-induced oxidative injury and mitochondrial dysfunction as well as via the up-regulation of nerve growth factor and antagonizing N-methyl-D-aspartate receptors. The most recent discovery that HupA may reduce brain iron accumulation lends further support to the argument that HupA could serve as a potential disease-modifying agent for AD and also other neurodegenerative disorders by significantly slowing down the course of neuronal death.

  14. Nanoparticle coating on the silane-modified surface of magnesium for local drug delivery and controlled corrosion.

    Science.gov (United States)

    Lee, Won Seok; Park, Min; Kim, Myung Hun; Park, Chun Gwon; Huh, Beom Kang; Seok, Hyun Kwang; Choy, Young Bin

    2016-01-01

    In this study, we proposed a potential method for the preparation of a magnesium-based medical device for local drug delivery and controlled corrosion. A magnesium surface was modified with 3-aminopropyltrimethoxy silane, and the resulting surface was then coated with drug-loaded nanoparticles made of poly (lactic-co-glycolic acid) via electrophoretic deposition. The drug-loaded nanoparticles (i.e., Tr_NP) exhibited a size of 250 ± 67 nm and a negative zeta potential of -20.9 ± 2.75 mV. The drug was released from the nanoparticles in a sustained manner for 21 days, and this did not change after their coating on the silane-modified magnesium. The silane-modified surface suppressed magnesium corrosion. When immersed in phosphate buffered saline at pH 7.4, the average rate of hydrogen gas generation was 0.41-0.45 ml/cm(2)/day, compared to 0.58-0.6 ml/cm(2)/day from a bare magnesium surface. This corrosion profile was not significantly changed after nanoparticle coating under the conditions employed in this work. The in vitro cell test revealed that the drug released from the coating was effective during the whole release period of 21 days, and both the silane-modified surface and carrier nanoparticles herein were not cytotoxic. © The Author(s) 2015.

  15. [Technological and pharmacotherapeutic properties of selected drugs with modified release of diclofenac sodium].

    Science.gov (United States)

    Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2012-01-01

    Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated. Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis. There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and

  16. FDM 3D printing of modified drug-delivery systems using hot melt extrusion: a new approach for individualized therapy.

    Science.gov (United States)

    Cunha-Filho, Marcilio; Araújo, Maísa Rp; Gelfuso, Guilherme M; Gratieri, Tais

    2017-11-01

    The production process of 3D-printed drugs offers unique advantages such as the possibility of individualizing the drug therapy and easily associating different drugs and release technologies in the same pharmaceutical unit. Fused deposition modeling, a 3D printing technique, seems especially interesting for pharmaceutical applications, due to its low cost, precise and reproducible control of the printed structures, and versatility for industrial and laboratory scale. This technique combined with another technology already adapted for the pharmaceutical industry, the hot melt extrusion, is able to incorporate various mechanisms of modified drug release. This special report aims to bring together data of the experimental progress achieved using the fused deposition modeling 3D printing combined with hot melt extrusion technique and its potential in drug delivery. [Formula: see text].

  17. [Therapeutic Concepts for Treatment of Patients with Non-infectious Uveitis Biologic Disease Modifying Antirheumatic Drugs].

    Science.gov (United States)

    Walscheid, Karoline; Pleyer, Uwe; Heiligenhaus, Arnd

    2018-04-12

    Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities. Currently, the TNF-α-inhibitor Adalimumab is the only in-label therapeutic option, whereas, all other bDMARDs need to be given as an off-label therapy. bDMARDs are indicated in diseases refractory to conventional synthetic DMARD therapy and/or systemic steroids, or in patients in whom treatment with those is not possible due to side effects. Therapeutic mechanisms currently employed are cytokine-specific (interferons, inhibition of TNF-α or of interleukin [IL]-1-, IL-6- or IL-17-signalling), inhibit T cell costimulation (CTLA-4 fusion protein), or act via depletion of B cells (anti-CD20). All bDMARDs need to be administered parenterally, and therapy is initiated by the treating internal specialist only after interdisciplinary coordination of all treating subspecialties and after exclusion of contraindications. Regular clinical and laboratory monitoring is mandatory for all patients while under bDMARD therapy. Georg Thieme Verlag KG Stuttgart · New York.

  18. Adherence to synthetic disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Results of the OBSERVAR Study.

    Science.gov (United States)

    Juan Mas, Antonio; Castañeda, Santos; Cantero Santamaría, José I; Baquero, José L; Del Toro Santos, Francisco J

    2017-12-27

    Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  19. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

    Science.gov (United States)

    Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

    2013-01-01

    Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

  20. A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Ruoxing Yu

    Full Text Available Mammalian fetal development is easily disrupted by exogenous agents, making it essential to test new drug candidates for embryotoxicity and teratogenicity. To standardize the testing of drugs that might be used to treat pregnant women, the U.S. Food and Drug Administration (FDA formulated special grade categories, labeled A, B, C, D and X, that define the level of risk associated with the use of a specific drug during pregnancy. Drugs in categories (Cat. D and X are those with embryotoxic and/or teratogenic effects on humans and animals. However, which stages of pregnancy are affected by these agents and their molecular mechanisms are unknown. We describe here an embryonic stem cell test (EST that classifies FDA pregnancy Cat.D and Cat.X drugs into 4 classes based on their differing effects on primitive streak formation. We show that ~84% of Cat.D and Cat.X drugs target this period of embryogenesis. Our results demonstrate that our modified EST can identify how a drug affects early embryogenesis, when it acts, and its molecular mechanism. Our test may thus be a useful addition to the drug safety testing armamentarium.

  1. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice

    International Nuclear Information System (INIS)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi; Tran, Van-Thanh; Duan, Wei; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    2016-01-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH 6.8 at 37 ± 0.5 °C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. - Highlights: • Modification process affected granule morphologies and flowability of modified rice. • Modification process affected swelling/erosion capacity for drug sustained release. • Freeze-drying could decrease the erosion as well as increase the swelling rate.

  2. Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drug-resistant ovarian cancer models

    Science.gov (United States)

    Apte, Anjali; Koren, Erez; Koshkaryev, Alexander; Torchilin, Vladimir P

    2014-01-01

    Multidrug resistance (MDR) is a hallmark of cancer cells and a crucial factor in chemotherapy failure, cancer reappearance, and patient deterioration. We have previously described the physicochemical characteristics and the in vitro anticancer properties of a multifunctional doxorubicin-loaded liposomal formulation. Lipodox®, a commercially available PEGylated liposomal doxorubicin, was made multifunctional by surface-decorating with a cell-penetrating peptide, TATp, conjugated to PEG1000-PE, to enhance liposomal cell uptake. A pH-sensitive polymer, PEG2000-Hz-PE, with a pH-sensitive hydrazone (Hz) bond to shield the peptide in the body and expose it only at the acidic tumor cell surface, was used as well. In addition, an anti-nucleosome monoclonal antibody 2C5 attached to a long-chain polymer to target nucleosomes overexpressed on the tumor cell surface was also present. Here, we report the in vitro cell uptake and cytotoxicity of the modified multifunctional immunoliposomes as well as the in vivo studies on tumor xenografts developed subcutaneously in nude mice with MDR and drug-sensitive human ovarian cancer cells (SKOV-3). Our results show the ability of multifunctional immunoliposomes to overcome MDR by enhancing cytotoxicity in drug-resistant cells, compared with non-modified liposomes. Furthermore, in comparison with the non-modified liposomes, upon intravenous injection of these multifunctional immunoliposomes into mice with tumor xenografts, a significant reduction in tumor growth and enhanced therapeutic efficacy of the drug in both drug-resistant and drug-sensitive mice was obtained. The use of “smart” multifunctional delivery systems may provide the basis for an effective strategy to develop, improve, and overcome MDR cancers in the future. PMID:24145298

  3. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam); Tran, Van-Thanh [Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City (Viet Nam); Duan, Wei [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Phuong Ha-Lien, E-mail: phuong.tran1@deakin.edu.au [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Thao Truong-Dinh, E-mail: ttdthao@hcmiu.edu.vn [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam)

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH 6.8 at 37 ± 0.5 °C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. - Highlights: • Modification process affected granule morphologies and flowability of modified rice. • Modification process affected swelling/erosion capacity for drug sustained release. • Freeze-drying could decrease the erosion as well as increase the swelling rate.

  4. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons

    DEFF Research Database (Denmark)

    Graudal, Niels; Jürgens, Gesche

    2010-01-01

    To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents.......To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents....

  5. Natural gum modified emulsion gel as single carrier for the oral delivery of probiotic-drug combination.

    Science.gov (United States)

    Pandey, S; Senthilguru, K; Uvanesh, K; Sagiri, S S; Behera, B; Babu, N; Bhattacharyya, M K; Pal, K; Banerjee, I

    2016-11-01

    Single formulation based delivery of probiotic-drug combination is envisioned as a superior therapeutic delivery modality for the diseases like Crohn's diseases, ulceritive colitis and Recurrent Clostridium difficile-Associated Diarrhoea (RCDAD). Keeping this perspective in mind, here we have developed natural gum [using a combination of aqueous solution of xantham gum (X) and guar gum (G)] modified sunflower oil based emulsion gels for the delivery of probiotics-drugs combination. FT-IR analysis and fluorescence microscopy together confirmed the formation of oil-in-water type emulsion gel by physical gelation in presence of the physical gelator sorbitan monopalmitate (SM). Other studies (XRD, DSC, mechanical properties and disintegration study) revealed that the variation in relative proportion of the two gums has a sporadic but significant effect on the physico-chemical properties of the gel. Post storage viability of commercially used probiotic Lactobacillus plantarum 299v (Lp 299v) at different storage conditions (4°C, -20°C, -196°C) was found higher in the emulsion gels with respect to the control. Moreover, the gels were found suitable for sustained delivery of metronidazole (the lipophilic drug often used with Lp 299v). In conclusion, the natural gum modified emulsion gel may be used as a delivery system for the probiotic-drug combination. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Increased Loading, Efficacy and Sustained Release of Silibinin, a Poorly Soluble Drug Using Hydrophobically-Modified Chitosan Nanoparticles for Enhanced Delivery of Anticancer Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Cha Yee Kuen

    2017-11-01

    Full Text Available Conventional delivery of anticancer drugs is less effective due to pharmacological drawbacks such as lack of aqueous solubility and poor cellular accumulation. This study reports the increased drug loading, therapeutic delivery, and cellular accumulation of silibinin (SLB, a poorly water-soluble phenolic compound using a hydrophobically-modified chitosan nanoparticle (pCNP system. In this study, chitosan nanoparticles were hydrophobically-modified to confer a palmitoyl group as confirmed by 2,4,6-Trinitrobenzenesulfonic acid (TNBS assay. Physicochemical features of the nanoparticles were studied using the TNBS assay, and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR analyses. The FTIR profile and electron microscopy correlated the successful formation of pCNP and pCNP-SLB as nano-sized particles, while Dynamic Light Scattering (DLS and Field Emission-Scanning Electron Microscopy (FESEM results exhibited an expansion in size between pCNP and pCNP-SLB to accommodate the drug within its particle core. To evaluate the cytotoxicity of the nanoparticles, a Methylthiazolyldiphenyl-tetrazolium bromide (MTT cytotoxicity assay was subsequently performed using the A549 lung cancer cell line. Cytotoxicity assays exhibited an enhanced efficacy of SLB when delivered by CNP and pCNP. Interestingly, controlled release delivery of SLB was achieved using the pCNP-SLB system, conferring higher cytotoxic effects and lower IC50 values in 72-h treatments compared to CNP-SLB, which was attributed to the hydrophobic modification of the CNP system.

  7. Drug delivery from hydrophobic-modified mesoporous silicas: Control via modification level and site-selective modification

    International Nuclear Information System (INIS)

    Tang Qunli; Chen Yuxi; Chen Jianghua; Li Jin; Xu Yao; Wu Dong; Sun Yuhan

    2010-01-01

    Dimethylsilyl (DMS) modified mesoporous silicas were successfully prepared via co-condensation and post-grafting modification methods. The post-grafting modification was carried out by the reaction of the as-synthesized MCM-41 material (before CTAB removal) with diethoxydimethylsinale (DEDMS). N 2 adsorption-desorption and 29 Si MAS NMR characterization demonstrated that different amount of DMS groups were successfully incorporated into the co-condensation modified samples, and the functional DMS groups were placed selectively on the pore openings and external pore surfaces in the post-grafting modified samples. Subsequently, the controlled drug delivery properties from the resulting DMS-modified mesoporous silicas were investigated in detail. The drug adsorption experiments showed that the adsorption capacities were mainly depended on the content of silanol group (CSG) in the corresponding carriers. The in vitro tests exhibited that the incorporation of DMS groups greatly retarded the ibuprofen release rate. Moreover, the ibuprofen release profiles could be well modulated by varying DMS modification levels and site-selective distribution of functional groups in mesoporous carriers. - The distribution of DMS groups on the pore surfaces of the mesostructures strongly affects the drug release rate. The P-M41-1 and the P-M41-2 possess the close DMS modification levels as the C-M41-10, but the ibuprofen release rates from the P-M41-1 and P-M41-2 are much slower than that from the C-M41-10.

  8. Modified MCM-41 as a drug delivery system for acetylsalicylic acid

    Science.gov (United States)

    Vyskočilová, Eliška; Luštická, Ivana; Paterová, Iva; Machová, Libuše; Červený, Libor

    2014-12-01

    The modification of prepared MCM-41 by different groups (amino, chloro and oxo) was studied. Prepared materials were treated by acetylsalicylic acid and hybrid materials were characterized, compared from the point of view of immobilized amount of active substance. The highest amount of acetylsalicylic acid was detected using methyl-tert- butyl ether as a solvent and MCM-41 without modification after 1 h (0.35 g per 1 g of the support) or MCM modified by amino group after 5 h (0.37 g per 1 g of the support) as a support. Using amino modified MCM, the longer treatment by acetylsalicylic acid converged to the equilibrium and after 24 h the immobilized amount was 0.3 g per 1 g. A dissolution in vitro study was carried out, comparing the stability of formed interactions. The slowest dissolution was detected using non-modified MCM-41 and oxo modified material.

  9. Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Jorge Enrique Machado-Alba

    2014-12-01

    Full Text Available This study describes the adverse drug reactions (ADRs and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART. A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years; these patients were from a cohort of 1 364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9. The cohort was mostly female (366, 87.4% and had a mean age of 52.7 years (± 13.1. The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively. The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.

  10. Pharmacological treatment of spondyloarthritis: exploring the effectiveness of nonsteroidal anti-inflammatory drugs, traditional disease-modifying antirheumatic drugs and biological therapies.

    Science.gov (United States)

    Caso, Francesco; Costa, Luisa; Del Puente, Antonio; Di Minno, Matteo Nicola Dario; Lupoli, Gelsy; Scarpa, Raffaele; Peluso, Rosario

    2015-11-01

    Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. The therapy target of spondyloarthritis relies mainly in improving patients' quality of life, controlling articular inflammation, preventing the structural joints damage and preserving the functional abilities, autonomy and social participation of patients. Among these, traditional disease-modifying antirheumatic drugs have been demonstrated to be effective in the management of peripheral arthritis; moreover, in the last decade, biological therapies have improved the approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α inhibitors are currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs has failed. The aim of this review is to summarize the current experience and evidence about the pharmacological approach in spondyloarthritis patients.

  11. The effect of comedication with conventional synthetic disease modifying antirheumatic drugs on TNF inhibitor drug survival in patients with ankylosing spondylitis and undifferentiated spondyloarthritis

    DEFF Research Database (Denmark)

    Lie, Elisabeth; Kristensen, Lars Erik; Forsblad-d'Elia, Helena

    2015-01-01

    OBJECTIVE: To assess the effect of comedication with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) on retention to tumour necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA). METHODS: Data...... on patients with a clinical diagnosis of AS or uSpA starting treatment with adalimumab, etanercept or infliximab as their first TNFi during 2003-2010 were retrieved from the Swedish national biologics register and linked to national population based registers. Five-year drug survival was analysed by Cox...... regression with age, sex, baseline csDMARD comedication, TNFi type, prescription year and covariates representing frailty and socioeconomic status. AS and uSpA were analysed separately. Sensitivity analyses included models with csDMARD as a time-dependent covariate and adjustments for additional potential...

  12. Nanoporous materials modified with biodegradable polymers as models for drug delivery applications

    DEFF Research Database (Denmark)

    Gruber, Mathias F; Schulte, Lars; Ndoni, Sokol

    2013-01-01

    Polymers play a central role in the development of carriers for diagnostic and therapeutic agents. Especially the use of either degradable polymers or porous materials to encapsulate drug compounds in order to obtain steady drug release profiles has received much attention. We present here a proof...... of principle for a system combining these two encapsulation methods and consisting of a nanoporous polymer (NP) with the pores filled with a degradable polymer mixed with a drug model. Rhodamine 6G (R6G) mixed with Poly(l-Lactic Acid) (PLLA) were confined within the 14nm pores of a NP with gyroid morphology...

  13. Amperometric sensing of anti-HIV drug zidovudine on Ag nanofilm-multiwalled carbon nanotubes modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Rafati, Amir Abbas, E-mail: aa_rafati@basu.ac.ir; Afraz, Ahmadreza

    2014-06-01

    The zidovudine (ZDV) is the first drug approved for the treatment of HIV virus infection. The detection and determination of this drug are very importance in human serum because of its undesirable effects. A new ZDV sensor was fabricated on the basis of nanocomposite of silver nanofilm (Ag-NF) and multiwalled carbon nanotubes (MWCNTs) immobilized on glassy carbon electrode (GCE). The modified electrodes were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), cyclic voltammetry (CV), and linear sweep voltammetry (LSV) techniques. Results showed that the electrodeposited silver has a nanofilm structure and further electrochemical studies showed that the prepared nanocomposite has high electrocatalytic activity and is appropriate for using in sensors. The amperometric technique under optimal conditions is used for the determination of ZDV ranging from 0.1 to 400 ppm (0.37 μM–1.5 mM) with a low detection limit of 0.04 ppm (0.15 μM) (S/N = 3) and good sensitivity. The prepared sensor possessed accurate and rapid response to ZDV and shows an average recovery of 98.6% in real samples. - Highlights: • New anti-HIV drug sensor was fabricated on the basis of nanomaterials composite. • The GCE modified by prepared hydrophilic MWCNT silver nanoparticles. • Silver nanofilm electrodeposited on MWCNT/GCE and characterized by SEM, EDX, CV and LSV • Response of electrode to ZDV was thoroughly investigated by electrochemical techniques.

  14. Assessing the effectiveness of synthetic and biologic disease-modifying antirheumatic drugs in psoriatic arthritis – a systematic review

    Directory of Open Access Journals (Sweden)

    Kingsley GH

    2015-05-01

    Full Text Available Gabrielle H Kingsley, David L Scott Rheumatology Unit, Kings College London, London, UK Background: Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published citing strategies for reducing disease progression, the evidence base for disease-modifying agents is unclear. This forms the focus of this systematic review. Methods: The systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 checklist. We selected randomized controlled trials (RCTs that looked at the impact of interventions with disease-modifying agents, either synthetic drugs or biologics on musculoskeletal outcomes, notably American College of Rheumatology 20 percent responders. Results were analyzed using Review Manager 5.1.6 (Cochrane Collaboration, Oxford, UK. Whilst our primary focus was on published trials, we also looked at new trials presented in abstract form in 2013–2014 that were not yet published to avoid omitting important and up-to-date information on developing treatments. Results: Our in-depth analysis included 28 trials overall enrolling 5,177 patients published between the 1980s and now as well as limited analysis of some studies in abstract form as described earlier. The most frequently available locomotor outcome measure was the American College of Rheumatology 20 percent responders. The risk ratio for achieving an American College of Rheumatology 20 percent responders response was positive in favor of treatment (risk ratio 2.30; 95% confidence interval 1.78–2.96; however, there was evidence of considerable heterogeneity between trials. Overall randomized controlled trials of established synthetic disease-modifying agents were largely negative (methotrexate, ciclosporin and sulfasalazine though leflunomide showed a small positive effect. A new synthetic agent, apremilast, did show a

  15. Synthesis of a novel thermo/pH sensitive nanogel based on salep modified graphene oxide for drug release

    International Nuclear Information System (INIS)

    Bardajee, Ghasem Rezanejade; Hooshyar, Zari; Farsi, Maryam; Mobini, Akram; Sang, Golnaz

    2017-01-01

    Nanogels (NGs) are three-dimensional water soluble cross-linked hydrogel materials in the nanoscale size range with a high loading capacity for guest molecules and act as drug carrier systems. In the present work, a new type of thermo/pH sensitive NG comprising salep modified graphene oxide (SMGO) with branched N-isopropylacrylamide (NIPAM) and acrylic acid (AA) was prepared. The SMGO/P(NIPAM-co-AA) NGs exhibited nanoporous structure and spherical particles with diameters about 82 nm as characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The samples were also characterized by Fourier transform infrared spectroscopy (FT-IR) and thermo gravimetric analysis (TGA) to further confirm about the formation of NGs. Doxorubicin (DOX) loaded SMGO/P(NIPAM-co-AA) NGs showed thermo/pH dependent releasing behavior: slow drug release at neutral pH and lower temperature but increased significantly in acidic pH and higher temperature, without any burst release. In addition, the NGs exhibited no effect on the cell viability in the tested concentration range up to 410 μg/mL and drug release systems enhanced toxicity to HeLa cells when compared to the equivalent dose of the free drug. Overall, our results put forth NGs as potential candidates in the development of a new nanocarrier for anti-cancer drug delivery. - Highlights: • A novel thermo/pH sensitive nanogels (NGs) was successfully synthesized. • NGs showed high loading capacity for DOX drug and slow drug release at neutral pH. • NGs exhibited no effect on the cell viability in the tested concentration range.

  16. Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

    Science.gov (United States)

    Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

    2016-01-01

    The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

  17. Fabrication and characterization of drug-loaded nano-hydroxyapatite/polyamide 66 scaffolds modified with carbon nanotubes and silk fibroin

    Science.gov (United States)

    Yao, Meng-Zhu; Huang-Fu, Ming-Yi; Liu, Hui-Na; Wang, Xia-Rong; Sheng, Xiaoxia; Gao, Jian-Qing

    2016-01-01

    Nano-hydroxyapatite/polyamide 66 (nHA/PA66) porous scaffolds were fabricated by a phase inversion method. Carbon nanotubes (CNTs) and silk fibroin (SF) were used to modify the surface of the nHA/PA66 scaffolds by freeze-drying and cross-linking. Dexamethasone was absorbed to the CNTs to promote the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). The cell viability of BMSCs was investigated by changing the concentration of the CNT dispersion, and the most biocompatible scaffold was selected. In addition, the morphology and mechanical property of the scaffolds were investigated. The results showed that the nHA/PA66 scaffolds modified with CNTs and SF met the requirements of bone tissue engineering scaffolds. The dexamethasone-loaded CNT/SF-nHA/PA66 composite scaffold promoted the osteogenic differentiation of BMSCs, and the drug-loaded scaffolds are expected to function as effective bone tissue engineering scaffolds. PMID:27920525

  18. Biosafety of Non-Surface Modified Carbon Nanocapsules as a Potential Alternative to Carbon Nanotubes for Drug Delivery Purposes

    Science.gov (United States)

    Tang, Alan C. L.; Hwang, Gan-Lin; Chang, Min-Yao; Tang, Zack C. W.; Tsai, Meng-Da; Luo, Chwan-Yao; Hoffman, Allan S.; Hsieh, Patrick C. H.

    2012-01-01

    Background Carbon nanotubes (CNTs) have found wide success in circuitry, photovoltaics, and other applications. In contrast, several hurdles exist in using CNTs towards applications in drug delivery. Raw, non-modified CNTs are widely known for their toxicity. As such, many have attempted to reduce CNT toxicity for intravenous drug delivery purposes by post-process surface modification. Alternatively, a novel sphere-like carbon nanocapsule (CNC) developed by the arc-discharge method holds similar electric and thermal conductivities, as well as high strength. This study investigated the systemic toxicity and biocompatibility of different non-surface modified carbon nanomaterials in mice, including multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), carbon nanocapsules (CNCs), and C60 fullerene (C60). The retention of the nanomaterials and systemic effects after intravenous injections were studied. Methodology and Principal Findings MWCNTs, SWCNTs, CNCs, and C60 were injected intravenously into FVB mice and then sacrificed for tissue section examination. Inflammatory cytokine levels were evaluated with ELISA. Mice receiving injection of MWCNTs or SWCNTs at 50 µg/g b.w. died while C60 injected group survived at a 50% rate. Surprisingly, mortality rate of mice injected with CNCs was only at 10%. Tissue sections revealed that most carbon nanomaterials retained in the lung. Furthermore, serum and lung-tissue cytokine levels did not reveal any inflammatory response compared to those in mice receiving normal saline injection. Conclusion Carbon nanocapsules are more biocompatible than other carbon nanomaterials and are more suitable for intravenous drug delivery. These results indicate potential biomedical use of non-surface modified carbon allotrope. Additionally, functionalization of the carbon nanocapsules could further enhance dispersion and biocompatibility for intravenous injection. PMID:22457723

  19. Modified Chitosan Nanoparticle by Radiation Synthesis: An Approach to Drug Delivery and Bio-Based Additive for Biomedical Applications

    International Nuclear Information System (INIS)

    Pasanphan, W.; Rimdusit, P.; Rattanawongwiboon, T.; Choofong, S.

    2010-01-01

    Self-assembly chitosan nanoparticle (CsNP) has been synthesized via radiolytic methodology using gamma irradiation. The systematic condition in preparation was studied. Chitosan nanoparticle was modified using hydrophobic core of deoxycholic acid (DC) and stearyl methacrylate (SMA) and the hydrophilic shell of polyethylene glycol monomethacrylate (PEG). The hydrophobic/hydrophilic CsNP was prepared for drug carrier molecule. The SMA-CsNP was also conjugated with pyperidine, hindered amine light stabilizer function, to achieve a bio-based additive for biomedical plastic. (author)

  20. Disease-modifying anti-rheumatic drugs til behandling af ankyloserende spondylitis

    DEFF Research Database (Denmark)

    Madsen, Ole Rintek; Egsmose, Charlotte

    2009-01-01

    , there is no evidence that disease-modifying anti-rheumatic (DMARDs) have a therapeutic effect in AS. Clinical evidence that greater TNF-inhibitor effectiveness can be achieved by combining with a DMARD is lacking, but further studies should be performed. More research is needed to clarify the role of DMARDs...

  1. The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

    Science.gov (United States)

    Barreira, Sofia Carvalho; Fonseca, João Eurico

    2016-08-01

    The bone and the immune system have a very tight interaction. Systemic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), induce bone loss, leading to a twofold increase in osteoporosis and an increase of fragility fracture risk of 1.35-2.13 times. This review focuses on the effects of conventional and biological disease modifying antirheumatic drugs (DMARDs) on bone biology, in the context of systemic inflammation, with a focus on RA. Published evidence supports a decrease in osteoclastic activity induced by DMARDs, which leads to positive effects on bone mineral density (BMD). It is unknown if this effect could be translated into fracture risk reduction. The combination with antiosteoclastic drugs can have an additional benefit.

  2. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    Science.gov (United States)

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors.

  3. Nanoporous materials modified with biodegradable polymers as models for drug delivery applications

    DEFF Research Database (Denmark)

    Gruber, Mathias F; Schulte, Lars; Ndoni, Sokol

    2013-01-01

    Polymers play a central role in the development of carriers for diagnostic and therapeutic agents. Especially the use of either degradable polymers or porous materials to encapsulate drug compounds in order to obtain steady drug release profiles has received much attention. We present here a proof...... of principle for a system combining these two encapsulation methods and consisting of a nanoporous polymer (NP) with the pores filled with a degradable polymer mixed with a drug model. Rhodamine 6G (R6G) mixed with Poly(l-Lactic Acid) (PLLA) were confined within the 14nm pores of a NP with gyroid morphology...... the hydrolysis of PLLA. The obtained release profiles demonstrate that the degradation of PLLA in nanoporous confinement is significantly slower than the degradation of unconfined PLLA. The release of R6G encapsulated in PLLA becomes correspondingly slower, while the initial burst release virtually disappears...

  4. Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

    Science.gov (United States)

    Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

    2017-09-01

    Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

  5. Nanoporous materials modified with biodegradable polymers as models for drug delivery applications.

    Science.gov (United States)

    Gruber, Mathias F; Schulte, Lars; Ndoni, Sokol

    2013-04-01

    Polymers play a central role in the development of carriers for diagnostic and therapeutic agents. Especially the use of either degradable polymers or porous materials to encapsulate drug compounds in order to obtain steady drug release profiles has received much attention. We present here a proof of principle for a system combining these two encapsulation methods and consisting of a nanoporous polymer (NP) with the pores filled with a degradable polymer mixed with a drug model. Rhodamine 6G (R6G) mixed with Poly(L-Lactic Acid) (PLLA) were confined within the 14 nm pores of a NP with gyroid morphology derived from a diblock copolymer precursor. Glass transition, crystallization and melting of free and confined PLLA were monitored by differential scanning calorimetry. Release profiles for R6G were measured in methanol-water solvents at pH 13, which works as an accelerated release test by speeding up the hydrolysis of PLLA. The obtained release profiles demonstrate that the degradation of PLLA in nanoporous confinement is significantly slower than the degradation of unconfined PLLA. The release of R6G encapsulated in PLLA becomes correspondingly slower, while the initial burst release virtually disappears. These findings suggest that the presented proof of principle constitutes a promising basis for the development of novel implantable drug delivery systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Cytostatic versus cytocidal profiling of quinoline drug combinations via modified fixed-ratio isobologram analysis

    Science.gov (United States)

    2013-01-01

    Background Drug combination therapy is the frontline of malaria treatment. There is an ever-accelerating need for new, efficacious combination therapies active against drug resistant malaria. Proven drugs already in the treatment pipeline, such as the quinolines, are important components of current combination therapy and also present an attractive test bank for rapid development of new concepts. Methods The efficacy of several drug combinations versus chloroquine-sensitive and chloroquine-resistant strains was measured using both cytostatic and cytocidal potency assays. Conclusions These screens identify quinoline and non-quinoline pairs that exhibit synergy, additivity, or antagonism using the fixed-ratio isobologram method and find tafenoquine – methylene blue combination to be the most synergistic. Also, interestingly, for selected pairs, additivity, synergy, or antagonism defined by quantifying IC50 (cytostatic potency) does not necessarily predict similar behaviour when potency is defined by LD50 (cytocidal potency). These data further support an evolving new model for quinoline anti-malarials, wherein haem and haemozoin are the principle target for cytostatic activity, but may not be the only target relevant for cytocidal activity. PMID:24044530

  7. Chemical Genetic Screens for TDP-43 Modifiers and ALS Drug Discovery

    Science.gov (United States)

    2015-03-01

    C011 hypericin antibiotic /kinases /DA B-hydroxylase D007 deoxyphorbol antitumour D011 mezerein antitumour/phorbol F003 genistein antihelmintic... Mexico (2012) P. Drapeau and A. Parker Chemical genetic screens of TARDBP and FUS modifiers in C. elegans and zebrafish. Keystone Conference ‘New...ECL Western Blotting Substrate (Thermo Scientific). Densitometry was performed with Photoshop (Adobe). Statistics For paralysis and stress- resistance

  8. Effect of penetration modifiers on the dermal and transdermal delivery of drugs and cosmetic active ingredients.

    Science.gov (United States)

    Otto, A; Wiechers, J W; Kelly, C L; Hadgraft, J; du Plessis, J

    2008-01-01

    In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation. Copyright 2008 S. Karger AG, Basel.

  9. Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers.

    Science.gov (United States)

    Kebebe, Dereje; Liu, Yuanyuan; Wu, Yumei; Vilakhamxay, Maikhone; Liu, Zhidong; Li, Jiawei

    2018-01-01

    Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

  10. Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

    OpenAIRE

    Lacramioara Ochiuz; Cristian Grigoras; Marcel Popa; Iulian Stoleriu; Corneliu Munteanu; Daniel Timofte; Lenuta Profire; Anca Giorgiana Grigoras

    2016-01-01

    The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifyin...

  11. Modelling drug degradation in a spray dried polymer dispersion using a modified Arrhenius equation.

    Science.gov (United States)

    Patterson, Adele; Ferreira, Ana P; Banks, Elizabeth; Skeene, Kirsty; Clarke, Graham; Nicholson, Sarah; Rawlinson-Malone, Clare

    2015-01-15

    The Pharmaceutical industry is increasingly utilizing amorphous technologies to overcome solubility challenges. A common approach is the use of drug in polymer dispersions to prevent recrystallization of the amorphous drug. Understanding the factors affecting chemical and physical degradation of the drug within these complex systems, e.g., temperature and relative humidity, is an important step in the selection of a lead formulation, and development of appropriate packaging/storage control strategies. The Arrhenius equation has been used as the basis of a number of models to predict the chemical stability of formulated product. In this work, we investigate the increase in chemical degradation seen for one particular spray dried dispersion formulation using hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Samples, prepared using polymers with different substitution levels, were placed on storage for 6 months under a range of different temperature and relative humidity conditions and the degradant level monitored using high-performance liquid chromatography (HPLC). While the data clearly illustrates the impact of temperature and relative humidity on the degradant levels detected, it also highlighted that these terms do not account for all the variability in the data. An extension of the Arrhenius equation to include a term for the polymer chemistry, specifically the degree of succinoyl substitution on the polymer backbone, was shown to improve the fit of the model to the data. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

    Directory of Open Access Journals (Sweden)

    Lacramioara Ochiuz

    2016-06-01

    Full Text Available The present paper focuses on solid lipid particles (SLPs, described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.

  13. PNIPAAM modified mesoporous hydroxyapatite for sustained osteogenic drug release and promoting cell attachment

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tao [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Tan, Lei [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Cheng, Ning; Yan, Qi; Zhang, Yu-Feng [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Liu, Chuan-Jun, E-mail: cjliu@whu.edu.cn [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Shi, Bin, E-mail: shibin_dentist@126.com [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China)

    2016-05-01

    This work presented a sustained release system of simvastatin (SIM) based on the mesoporous hydroxyapatite (MHA) capped with poly(N-isopropylacrylamide) (PNIPAAM). The MHA was prepared by using cetyltrimethylammonium bromide (CTAB) as a template and the modified PNIPAAM layer on the surface of MHA was fabricated through surface-initiated atom transfer radical polymerization (SI-ATRP). The SIM loaded MHA-PNIPAAM showed a sustained release of SIM at 37 °C over 16 days. The bone marrow mesenchymal stem cell (BMSC) proliferation was assessed by cell counting kit-8 (CCK-8) assay, and the osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red staining. The release profile showed that the release of SIM from MHA-SIM-PNIPAAM lasted 16 days and the cumulative amount of released SIM was almost seven-fold than MHA-SIM. Besides, SIM loaded MHA-PNIPAAM exhibited better performance on cell proliferation, ALP activity, and calcium deposition than pure MHA due to the sustained release of SIM. The quantity of ALP in MHA-SIM-PNIPAAM group was more than two fold than pure MHA group at 7 days. Compared to pure MHA, better BMSC attachment on PNIPAAM modified MHA was observed using fluorescent microscopy, indicating the better biocompatibility of MHA-PNIPAAM. - Highlights: • PNIPAAM modified mesoporous hydroxyapatite (MHA) was fabricated by SI-ATRP. • SIM loaded MHA-PNIPAAM continually released SIM in effect concentration for 16 days. • MHA-SIM-PNIPAAM behaved well on cell proliferation, ALP activity and calcium deposition.

  14. Electrochemical behavior of an anticancer drug 5-fluorouracil at methylene blue modified carbon paste electrode

    International Nuclear Information System (INIS)

    Bukkitgar, Shikandar D.; Shetti, Nagaraj P.

    2016-01-01

    A novel sensor for the determination of 5-fluorouracil was constructed by electrochemical deposition of methylene blue on surface of carbon paste electrode. The electrode surface morphology was studied using Atomic force microscopy and XRD. The electrochemical activity of modified electrode was characterized using cyclic voltammetry and differential pulse method. The developed sensor shows impressive enlargement in sensitivity of 5-fluorouracil determination. The peak currents obtained from differential pulse voltammetry was linear with concentration of 5-fluorouracil in the range 4 × 10 −5 –1 × 10 −7 M and detection limit and quantification limit were calculated to be 2.04 nM and 6.18 nM respectively. Further, the sensor was successfully applied in pharmaceutical and biological fluid sample analysis. - Highlights: • Electrochemical oxidation of 5-fluorouracil has been investigated for first time at methylene blue modified carbon paste electrode • The electrode process was irreversible and diffusion controlled • Probable electrochemical mechanism was proposed which involved two proton and two electron transfer reaction • The LOD and LOQ values were calculated to be 2.04 nM and 6.18 nM, respectively, with good selectivity and sensitivity. • Proposed method was applied to 5-Fluorouracil determination in pharmaceutical and spiked human urine samples

  15. Electrochemical behavior of an anticancer drug 5-fluorouracil at methylene blue modified carbon paste electrode

    Energy Technology Data Exchange (ETDEWEB)

    Bukkitgar, Shikandar D.; Shetti, Nagaraj P., E-mail: dr.npshetti@gmail.com

    2016-08-01

    A novel sensor for the determination of 5-fluorouracil was constructed by electrochemical deposition of methylene blue on surface of carbon paste electrode. The electrode surface morphology was studied using Atomic force microscopy and XRD. The electrochemical activity of modified electrode was characterized using cyclic voltammetry and differential pulse method. The developed sensor shows impressive enlargement in sensitivity of 5-fluorouracil determination. The peak currents obtained from differential pulse voltammetry was linear with concentration of 5-fluorouracil in the range 4 × 10{sup −5}–1 × 10{sup −7} M and detection limit and quantification limit were calculated to be 2.04 nM and 6.18 nM respectively. Further, the sensor was successfully applied in pharmaceutical and biological fluid sample analysis. - Highlights: • Electrochemical oxidation of 5-fluorouracil has been investigated for first time at methylene blue modified carbon paste electrode • The electrode process was irreversible and diffusion controlled • Probable electrochemical mechanism was proposed which involved two proton and two electron transfer reaction • The LOD and LOQ values were calculated to be 2.04 nM and 6.18 nM, respectively, with good selectivity and sensitivity. • Proposed method was applied to 5-Fluorouracil determination in pharmaceutical and spiked human urine samples.

  16. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid in Simulated Intestinal Fluids.

    Directory of Open Access Journals (Sweden)

    Patrik Knöös

    Full Text Available A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium or fed state (FeSSIF. The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

  17. Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis.

    Science.gov (United States)

    Filippini, Graziella; Del Giovane, Cinzia; Clerico, Marinella; Beiki, Omid; Mattoscio, Miriam; Piazza, Federico; Fredrikson, Sten; Tramacere, Irene; Scalfari, Antonio; Salanti, Georgia

    2017-04-25

    The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions. 1. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for the treatment of a first clinical attack suggestive of MS compared either with placebo or no treatment;2. to assess the relative efficacy and safety of disease-modifying drugs according to their benefit and safety;3. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for treatment started after a first attack ('early treatment') compared with treatment started after a second attack or at another later time point ('delayed treatment'). We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Trials Register, MEDLINE, Embase, CINAHL, LILACS, clinicaltrials.gov, the WHO trials registry, and US Food and Drug Administration (FDA) reports, and searched for unpublished studies (until December 2016). We included randomised and observational studies that evaluated one or more drugs as monotherapy in adult participants with a first clinical attack suggestive of MS. We considered evidence on alemtuzumab, azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1b, interferon beta-1a (Rebif®, Avonex®), laquinimod, mitoxantrone, natalizumab, ocrelizumab, pegylated interferon beta-1a, rituximab and

  18. Receptor changes and LTP: an analysis using aniracetam, a drug that reversibly modifies glutamate (AMPA) receptors.

    Science.gov (United States)

    Staubli, U; Ambros-Ingerson, J; Lynch, G

    1992-01-01

    The hypothesis that long-term potentiation (LTP) involves receptor modifications was tested with aniracetam, a nootropic drug that selectively increases currents mediated by the AMPA subclass of glutamate receptors. Aniracetam had different effects on the waveform of synaptic potentials in hippocampus before and after induction of LTP: (1) the drug caused a slight reduction (or delay) of the initial segment of the response after LTP; and (2) the facilitatory effects of aniracetam occurred at a later time point in the response after LTP than before. The interactions between LTP and aniracetam were still present when synaptic responses were greatly reduced by partial blockade of postsynaptic receptors and were not reproduced by increasing release or the number of stimulated synapses. A mathematical treatment of synaptic currents produced the following results: (1) if aniracetam facilitates AMPA receptor currents simply by reducing desensitization, then its complex interaction with LTP emerges when potentiation changes the kinetic and conductance properties of receptor channels; (2) if aniracetam also significantly increases conductance, then the experimental data can be reproduced by modeling LTP as an increase in channel conductance alone.

  19. Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges.

    Science.gov (United States)

    Gulati, Karan; Ivanovski, Sašo

    2017-08-01

    The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO 2 nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization. Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity. Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.

  20. Multifunctional hyaluronic acid modified graphene oxide loaded with mitoxantrone for overcoming drug resistance in cancer

    Science.gov (United States)

    Hou, Lin; Feng, Qianhua; Wang, Yating; Yang, Xiaomin; Ren, Junxiao; Shi, Yuyang; Shan, Xiaoning; Yuan, Yujie; Wang, Yongchao; Zhang, Zhenzhong

    2016-01-01

    Multifunctional nanosheets (HA-GO/Pluronic) with targeted chemo-photothermal properties were successfully developed for controlled delivery of mitoxantrone (MIT) to overcome multidrug resistance (MDR). In vitro release profiles displayed that both an acidic environment and a NIR laser could trigger and accelerate the release of a drug, which ensured nanosheets were stable in blood circulation and released MIT within tumor cells under laser irradiation. HA-GO/Pluronic nanosheets were taken up into MCF-7/ADR cells via receptor-mediated endocytosis, which further facilitated escapement of P-gp efflux. Compared with MIT solution, MIT/HA-GO/Pluronic showed greater cytotoxicity and increase in cellular MIT accumulation in MCF-7/ADR cells. Cell apoptosis and cell cycle arrest studies also revealed that MIT/HA-GO/Pluronic was more potent than MIT/GO/Pluronic and MIT solution. The anticancer efficacy in vivo was evaluated in MCF-7 and MCF-7/ADR-bearing mice, and inhibition of tumors by MIT/HA-GO/Pluronic with NIR laser irradiation was the most effective among all MIT formulations. In summary, the MIT/HA-GO/Pluronic system had striking functions such as P-gp reversible inhibitor and anticancer efficacy, and could present a promising platform for drug-resistant cancer treatment.

  1. “Smart” Drug Carriers: PEGylated TATp-Modified pH-Sensitive Liposomes

    Science.gov (United States)

    KALE, AMIT A.; TORCHILIN, VLADIMIR P.

    2012-01-01

    To engineer drug carriers capable of spontaneous accumulation in tumors and ischemic areas via the enhanced permeability and retention (EPR) effect and further penetration and drug delivery inside tumor or ischemic cells via the action of the cell-penetrating peptide (CPP), we have prepared liposomes simultaneously bearing on their surface CPP (TAT peptide, TATp) moieties and protective PEG chains. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE). Under normal conditions, liposome-grafted PEG “shielded” liposome-attached TATp moieties since the PEG spacer for TATp attachment (PEG1000) was shorter than protective PEG2000. PEGy-lated liposomes are expected to accumulate in targets via the EPR effect, but inside the “acidified” tumor or ischemic tissues lose their PEG coating due to the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. This concept is shown here to work in cell cultures in vitro as well as in ischemic cardiac tissues in the Langendorff perfused rat heart model and in tumors in experimental mice in vivo. PMID:18027240

  2. "Smart" drug carriers: PEGylated TATp-modified pH-sensitive liposomes.

    Science.gov (United States)

    Kale, Amit A; Torchilin, Vladimir P

    2007-01-01

    To engineer drug carriers capable of spontaneous accumulation in tumors and ischemic areas via the enhanced permeability and retention (EPR) effect and further penetration and drug delivery inside tumor or ischemic cells via the action of the cell-penetrating peptide (CPP), we have prepared liposomes simultaneously bearing on their surface CPP (TAT peptide, TATp) moieties and protective PEG chains. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE). Under normal conditions, liposome-grafted PEG "shielded" liposome-attached TATp moieties since the PEG spacer for TATp attachment (PEG(1000)) was shorter than protective PEG(2000). PEGylated liposomes are expected to accumulate in targets via the EPR effect, but inside the "acidified" tumor or ischemic tissues lose their PEG coating due to the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. This concept is shown here to work in cell cultures in vitro as well as in ischemic cardiac tissues in the Langendorff perfused rat heart model and in tumors in experimental mice in vivo.

  3. Is drug insurance status an effect modifier in epidemiologic database studies? The case of maternal asthma and major congenital malformations.

    Science.gov (United States)

    Blais, Lucie; Kettani, Fatima-Zohra; Forget, Amélie; Beauchesne, Marie-France; Lemière, Catherine

    2015-12-01

    Our previous work on the association between maternal asthma and congenital malformations was based on cohorts formed by women with public drug insurance, i.e., over-represented by women with lower socioeconomic status, questioning the generalizability of our findings. This study aimed to evaluate whether or not drug insurance status, as a proxy of socioeconomic status, is an effect modifier for the association between maternal asthma and major congenital malformations. A cohort of 36,587 pregnancies from asthmatic women and 198,935 pregnancies from nonasthmatic women selected independently of their drug insurance status was reconstructed with Québec administrative databases (1998-2009). Asthmatic women were identified using a validated case definition of asthma. Cases of major congenital malformations were identified using diagnostic codes recorded in the hospitalization database. Drug insurance status at the beginning of pregnancy was classified into three groups: publicly insured with social welfare, publicly insured without social welfare, and privately insured. Adjusted odds ratios were estimated with generalized estimation equations, including an interaction term between maternal asthma and drug insurance status. The prevalence of congenital malformations was 6.8% among asthmatic women and 5.8% among nonasthmatics. The impact of asthma on the prevalence of congenital malformations was significantly greater in women publicly insured with social welfare (odds ratio = 1.42; 95% confidence interval, 1.25-1.61) than in the other two groups ([odds ratio = 1.10; 1.00-1.21] in the publicly insured without social welfare and [odds ratio = 1.13; 1.07-1.20] in the privately insured group). The increased risk of major congenital malformation associated with asthma was significantly higher among pregnant women publicly insured with social welfare than among those privately insured. As a result of this effect modification by drug insurance status, findings

  4. Biologic Disease-Modifying Antirheumatic Drugs in a National, Privately Insured Population: Utilization, Expenditures, and Price Trends.

    Science.gov (United States)

    Atzinger, Christopher B; Guo, Jeff J

    2017-02-01

    Spending on biologic drugs is a significant driver of drug expenditures for payers in private health plans. Biologic disease-modifying antirheumatic drugs (DMARDs) are some of the most effective and costly treatments in a physician's arsenal. Understanding the total annual expenditure, the average cost per prescription, and the impact of cost-sharing is important for drug benefit managers. To assess drug utilization, expenditures, out-of-pocket (OOP) cost, and price trends of biologic DMARDs in patients with rheumatoid arthritis (RA) in a large managed care organization. We conducted a retrospective database analysis of pharmacy claims data from January 2004 to December 2013 using the Optum Clinformatics Data Mart database, which covers 13.3 million lives. Pharmacy claims for 40,373 patients with RA were identified during the study period. In all, 9 biologic DMARDs approved for the treatment of RA, including infliximab, etanercept, adalimumab, certoizumab, golimumab, tocilizumab, anakinra, abatacept, and rituximab, and 1 nonbiologic oral, small molecule-targeted synthetic drug, tofacitinib, were included in this study. Descriptive statistics were used to analyze the total annual number of prescriptions, the total annual expenditures, the average annual cost per drug (a proxy of drug price), and the average OOP cost (copay plus deductible and coinsurance). All measurements were also stratified by study drugs and by insurance type. Of the 40,373 patients with RA included in the study, approximately 76% were female (mean age, 55 years at diagnosis). Approximately 77% of the patients were white, and almost 48% lived in the South or Midwest region of the United States. Approximately 62% of patients had a point of service insurance plan. Expenditures on biologic DMARDs increased from $166 million in 2004 to $243 million in 2013, and the number of prescriptions and refills increased from 59,960 in 2004 to 105,295 in 2013. Prescriptions for biologic DMARDs increased more

  5. Sonication-Based Improvement of the Physicochemical Properties of Guar Gum as a Potential Substrate for Modified Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Siddique Akber Ansari

    2013-01-01

    Full Text Available Guar Gum is a natural polysaccharide that, due to its physicochemical properties, is extensively investigated for biomedical applications as a matrix for modified drug delivery, but it is also used in the food industry as well as in cosmetics. A commercial sample of Guar Gum was sonicated for different periods of time, and the reduction in the average molecular weight was monitored by means of viscometric measurements. At the same time, the rheological behaviour was also followed, in terms of viscoelasticity range, flow curves, and mechanical spectra. Sonicated samples were used for the preparation of gels in the presence of borate ions. The effect of borax on the new samples was investigated by recording mechanical spectra, flow curves, and visible absorption spectra of complexes with Congo Red. The anisotropic elongation, observed in previous studies with tablets of Guar Gum and borax, was remarkably reduced when the sonicated samples were used for the preparation of the gels.

  6. Disease-Modifying Drug Possibly Linked to Placental Insufficiency; Severe placental complications in a pregnant woman with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Sultan M. Salahudheen

    2016-08-01

    Full Text Available Disease-modifying drugs (DMDs such as interferon (IFN-β and glatiramer acetate are often prescribed to slow disability progression in patients with multiple sclerosis (MS. However, adverse pregnancy outcomes have been reported with these medications. We report the rare occurrence of severe placental complications in a 30-yearold pregnant woman with MS who continued to take IFN-β during her first trimester. She presented at the Tawam Hospital, Al Ain, United Arab Emirates, in 2013 with early-onset fetal growth restriction. At 30 gestational weeks, she developed severe pre-eclampsia. The baby was delivered via emergency Caesarean section and was discharged at the age of two months. Continuation of IFN-β during pregnancy may have contributed to the development of placental insufficiency in this patient. Increased education regarding the risks of DMDs for pregnant patients with MS is very important to ensure successful pregnancy outcomes.

  7. Voltammetric Determination of Anti-Hypertensive Drug Hydrochlorothiazide Using Screen-Printed Electrodes Modified with L-Glutamic Acid

    Directory of Open Access Journals (Sweden)

    Camilo González-Vargas

    2017-09-01

    Full Text Available This work deals with the development of screen-printed carbon electrodes modified with L-glutamic acid via two different approaches: electropolymerization (SPCE/PGA and aryl diazonium electrochemical grafting (SPCE/EGA. SPCE/PGA and SPCE/EGA were analytically compared in the determination of hydrochlorothiazide (HCTZ by differential pulse voltammetry. Both electrochemical characterization and analytical performance indicate that SPCE/EGA is a much better sensor for HCTZ. The detection and quantification limits were at the level of μmol L−1 with a very good linearity in the studied concentration range. In addition, the proposed SPCE/EGA was successfully applied for the determination of HCTZ in an anti-hypertensive drug with high reproducibility and good trueness.

  8. Novel Hydrogel-Advanced Modified Clay Nanocomposites as Possible Vehicles for Drug Delivery and Controlled Release

    Directory of Open Access Journals (Sweden)

    Raluca Ianchis

    2017-12-01

    Full Text Available Present study refers to the synthesis of new advanced materials based on poly(methacrylic acid (PMAA with previously reported own advanced modified clays by edge covalent bonding. This will create the premises to obtain nanocomposite hydrogels with combined hydrophilic-hydrophobic behavior absolutely necessary for co-delivery of polar/nonpolar substances. For the synthesis, N,N’-methylenebisacrylamide was used as cross-linker and ammonium persulphate as initiator. As a consequence of the inclusion of clay into the polymer matrix and the intercalation of PMAA between the layers as well as the presence of hydrophobic interactions occurred between partners, the final hydrogel nanocomposites possessed greater swelling degrees, slower de-swelling process and enhanced mechanical properties depending on the clay type in comparison with pure hydrogel. In vitro MTS ([3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, inner salt] colorimetric assay showed that direct exposure with PMMA-clay-based constructs did not affect cell viability and proliferation in time (24 and 48 h on either normal or adenocarcinoma cell lines.

  9. Novel Hydrogel-Advanced Modified Clay Nanocomposites as Possible Vehicles for Drug Delivery and Controlled Release.

    Science.gov (United States)

    Ianchis, Raluca; Ninciuleanu, Claudia M; Gifu, Ioana C; Alexandrescu, Elvira; Somoghi, Raluca; Gabor, Augusta R; Preda, Silviu; Nistor, Cristina L; Nitu, Sabina; Petcu, Cristian; Icriverzi, Madalina; Florian, Paula E; Roseanu, Anca M

    2017-12-13

    Present study refers to the synthesis of new advanced materials based on poly(methacrylic acid) (PMAA) with previously reported own advanced modified clays by edge covalent bonding. This will create the premises to obtain nanocomposite hydrogels with combined hydrophilic-hydrophobic behavior absolutely necessary for co-delivery of polar/nonpolar substances. For the synthesis, N , N '-methylenebisacrylamide was used as cross-linker and ammonium persulphate as initiator. As a consequence of the inclusion of clay into the polymer matrix and the intercalation of PMAA between the layers as well as the presence of hydrophobic interactions occurred between partners, the final hydrogel nanocomposites possessed greater swelling degrees, slower de-swelling process and enhanced mechanical properties depending on the clay type in comparison with pure hydrogel. In vitro MTS ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium, inner salt]) colorimetric assay showed that direct exposure with PMMA-clay-based constructs did not affect cell viability and proliferation in time (24 and 48 h) on either normal or adenocarcinoma cell lines.

  10. Novel Therapeutic Targets and Drug Candidates for Modifying Disease Progression in Adrenoleukodystrophy.

    Science.gov (United States)

    Pujol, Aurora

    2016-01-01

    X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease. It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of very-long-chain fatty acids (VLCFA) in organs and plasma. Recent findings on pathomechanisms of the peroxisomal neurometabolic disease X-ALD have provided important clues on therapeutic targets. Here we describe the impact of chronic redox imbalance caused by the excess VLCFA on mitochondrial biogenesis and respiration, and explore the consequences on the protein quality control systems essential for cell survival, such as the proteasome and autophagic flux. Defective proteostasis, together with mitochondrial malfunction, is a hallmark of the most prevalent neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and of the aging process. Thus, we discuss molecular targets and emerging treatment options that may be common to both multifactorial neurodegenerative disorders and X-ALD. New-generation antioxidants, some of them mitochondrial targeted, mitochondrial biogenesis boosters such as pioglitazone and resveratrol, and the mTOR inhibitor temsirolimus hold promise as disease-modifying therapies. © 2016 S. Karger AG, Basel.

  11. Insights into RNA binding by the anticancer drug cisplatin from the crystal structure of cisplatin-modified ribosome

    Science.gov (United States)

    Melnikov, Sergey V.; Söll, Dieter; Steitz, Thomas A.

    2016-01-01

    Abstract Cisplatin is a widely prescribed anticancer drug, which triggers cell death by covalent binding to a broad range of biological molecules. Among cisplatin targets, cellular RNAs remain the most poorly characterized molecules. Although cisplatin was shown to inactivate essential RNAs, including ribosomal, spliceosomal and telomeric RNAs, cisplatin binding sites in most RNA molecules are unknown, and therefore it remains challenging to study how modifications of RNA by cisplatin contributes to its toxicity. Here we report a 2.6Å-resolution X-ray structure of cisplatin-modified 70S ribosome, which describes cisplatin binding to the ribosome and provides the first nearly atomic model of cisplatin–RNA complex. We observe nine cisplatin molecules bound to the ribosome and reveal consensus structural features of the cisplatin-binding sites. Two of the cisplatin molecules modify conserved functional centers of the ribosome—the mRNA-channel and the GTPase center. In the mRNA-channel, cisplatin intercalates between the ribosome and the messenger RNA, suggesting that the observed inhibition of protein synthesis by cisplatin is caused by impaired mRNA-translocation. Our structure provides an insight into RNA targeting and inhibition by cisplatin, which can help predict cisplatin-binding sites in other cellular RNAs and design studies to elucidate a link between RNA modifications by cisplatin and cisplatin toxicity. PMID:27079977

  12. Modified hydrotalcite-like compounds as active fillers of biodegradable polymers for drug release and food packaging applications.

    Science.gov (United States)

    Costantino, Umberto; Nocchetti, Morena; Tammaro, Loredana; Vittoria, Vittoria

    2012-11-01

    This review treats the recent patents and related literature, mainly from the Authors laboratories, on biomedical and food packaging applications of nano-composites constituted of biodegradable polymers filled with micro or nano crystals of organically modified Layered Double Hydroxides of Hydrotalcite type. After a brief outline of the chemical and structural aspects of Hydrotalcite-like compounds (HTlc) and of their manipulation via intercalation of functional molecular anions to obtain materials for numerous, sometime unexpected applications, the review approaches the theme in three separated parts. Part 1 deals with the synthetic method used to prepare the pristine Mg-Al and Zn-Al HTlc and with the procedures of their functionalization with anti-inflammatory (diclofenac), antibacterial (chloramphenicol hemisuccinate), antifibrinolytic (tranexamic acid) drugs and with benzoates with antimicrobial activity. Procedures used to form (nano) composites of polycaprolactone, used as an example of biodegradable polymer, and functionalized HTlc are also reported. Part 2 discusses a patent and related papers on the preparation and biomedical use of a controlled delivery system of the above mentioned pharmacologically active substances. After an introduction dealing with the recent progress in the field of local drug delivery systems, the chemical and structural aspects of the patented system constituted of a biodegradable polymer and HTlc loaded with the active substances will be presented together with an extensive discussion of the drug release in physiological medium. Part 3 deals with a recent patent and related papers on chemical, structural and release property of antimicrobial species of polymeric films containing antimicrobial loaded HTlc able to act as active packaging for food products prolonging their shelf life.

  13. Cyclic RGD peptide-modified liposomal drug delivery system: enhanced cellular uptake in vitro and improved pharmacokinetics in rats

    Directory of Open Access Journals (Sweden)

    Chen Z

    2012-07-01

    Full Text Available Zhongya Chen,1,2 Jiaxin Deng,1,2 Yan Zhao,1,2 Tao Tao1,21National Pharmaceutical Engineering Research Center, 2Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaBackground: Integrins αvβ3 and αvβ5, both of which specifically recognize the Arg-Gly-Asp (RGD motif, are overexpressed on many solid tumors and in tumor neovasculature. Thus, coupling the RGD motif to the liposomal surface for achieving active targeting can be a promising strategy for the treatment of tumors.Methods: Cyclo(Arg-Gly-Asp-D-Phe-Cys (cRGD was covalently coupled with the liposomal membrane surface, followed by coating with poly(ethylene glycol (PEG using the post-insertion technique. The coupling efficiency of cRGD was determined. Doxorubicin as a model anticancer drug was loaded into liposomes using an ammonium sulfate gradient method to investigate the encapsulation efficiency, cellular uptake by the integrin-overexpressing human glioma cell line U87MG in vitro, and pharmacokinetic properties in Sprague-Dawley rats.Results: cRGD was conjugated to the liposomal surface by a thiol-maleimide coupling reaction. The coupling efficiency reached 98%. The encapsulation efficiency of doxorubicin in liposomes was more than 98%. The flow cytometry test result showed that cRGD-modified liposomes (RGD-DXRL-PEG had higher cell uptake by U87MG cells, compared with nontargeted liposomes (DXRL-PEG. The cellular uptake was significantly inhibited in the presence of excess free cRGD. Both the targeted (t1/2 = 24.10 hours and non-targeted (t1/2 = 25.32 hours liposomes showed long circulating properties in rat plasma. The area under the curve of the targeted and nontargeted liposomes was 6.4-fold and 8.3-fold higher than that of doxorubicin solution, respectively.Conclusion: This study indicates preferential targeting and long circulating properties for cRGD-modified liposomes in vivo, which could be used as

  14. Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment

    NARCIS (Netherlands)

    Schiff, Michael; Takeuchi, Tsutomu; Fleischmann, Roy; Gaich, Carol L.; DeLozier, Amy M.; Schlichting, Douglas; Kuo, Wen-Ling; Won, Ji-Eon; Carmack, Tara; Rooney, Terence; Durez, Patrick; Shaikh, Saeed; Hidalgo, Rodolfo Pardo; van Vollenhoven, Ronald; Zerbini, Cristiano A. F.

    2017-01-01

    This study evaluates patient-reported outcomes (PROs) in a double-blind, phase III study of baricitinib as monotherapy or combined with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) with no or minimal prior conventional synthetic disease-modifying antirheumatic drugs (DMARDs)

  15. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis

    NARCIS (Netherlands)

    Nam, Jackie L.; Ramiro, Sofia; Gaujoux-Viala, Cecile; Takase, Kaoru; Leon-Garcia, Mario; Emery, Paul; Gossec, Laure; Landewe, Robert; Smolen, Josef S.; Buch, Maya H.

    2014-01-01

    To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism(EULAR) Task Force treatment recommendations. Medline, Embase and Cochrane databases were searched for

  16. An Evidence-Based Assessment of the Clinical Significance of Drug-Drug Interactions Between Disease-Modifying Antirheumatic Drugs and Non-Antirheumatic Drugs According to Rheumatologists and Pharmacists

    NARCIS (Netherlands)

    van Roon, Eric N.; van den Bemt, Patricia M. L. A.; Jansen, Tim L. Th. A.; Houtman, Nella M.; van de Laar, Mart A. F. J.; Brouwers, Jacobus R. B. J.

    Background: Clinically relevant drug-drug interactions (DDIs) must be recognized in a timely manner and managed appropriately to prevent adverse drug reactions or therapeutic failure. Because the evidence for most DDIs is based on case reports or poorly documented clinical information, there is a

  17. Comparative QSAR studies on PAMPA/modified PAMPA for high throughput profiling of drug absorption potential with respect to Caco-2 cells and human intestinal absorption

    Science.gov (United States)

    Verma, Rajeshwar P.; Hansch, Corwin; Selassie, Cynthia D.

    2007-01-01

    Despite the dramatic increase in speed of synthesis and biological evaluation of new chemical entities, the number of compounds that survive the rigorous processes associated with drug development is low. Thus, an increased emphasis on thorough ADMET (absorption, distribution, metabolism, excretion and toxicity) studies based on in vitro and in silico approaches allows for early evaluation of new drugs in the development phase. Artificial membrane permeability measurements afford a high throughput, relatively low cost but labor intensive alternative for in vitro determination of drug absorption potential; parallel artificial membrane permeability assays have been extensively utilized to determine drug absorption potentials. The present study provides comparative QSAR analysis on PAMPA/modified PAMPA for high throughput profiling of drugs with respect to Caco-2 cells and human intestinal absorption.

  18. Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding

    Directory of Open Access Journals (Sweden)

    Luisa Rocha

    2008-06-01

    Full Text Available Luisa RochaPharmacobiology Department, Center for Research and Advanced Studies, Calz, Tenorios, MéxicoAbstract: Experiments using male CD1 mice were carried out to investigate the effects of subchronic (daily administration for 8 days pretreatments with drugs enhancing GABAergic transmission (diazepam, 10 mg/kg, ip; gabapentin, 100 mg/kg, po; or vigabatrin, 500 mg/kg, po on pentylenetetrazol (PTZ-induced seizures, 24 h after the last injection. Subchronic administration of diazepam reduced latencies to clonus, tonic extension and death induced by PTZ. Subchronic vigabatrin produced enhanced latency to the first clonus but faster occurrence of tonic extension and death induced by PTZ. Subchronic gabapentin did not modify PTZ-induced seizures. Autoradiography experiments revealed reduced benzodiazepine receptor binding in several brain areas after subchronic treatment with diazepam or gabapentin, whereas subchronic vigabatrin did not induce significant receptor changes. The present results indicate differential effects induced by the subchronic administration of diazepam, vigabatrin, and gabapentin on the susceptibility to PTZ-induced seizures, benzodiazepine receptor binding, or both.Keywords: diazepam, gabapentin, vigabatrin, pentylenetetrazol, benzodiazepine receptors

  19. Preparation of β-cyclodextrin-gold nanoparticles modified open tubular column for capillary electrochromatographic separation of chiral drugs.

    Science.gov (United States)

    Zhou, Li; Jiang, Shenmeng; Zhang, Xue; Fang, Linlin; Guo, Xingjie

    2018-04-01

    In this paper, β-cyclodextrin (β-CD) modified gold nanoparticles (AuNPs) coated open tubular column (OT column) was prepared for capillary electrochromatography. The open tubular column was constructed through self-assembly of gold nanoparticles on 3-mercaptopropyl-trimethoxysilane (MPTMS) prederivatized capillary and subsequent modification of thiols β-cyclodextrin (SH-β-CD). Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and ultraviolet visible spectroscopy were carried out to characterize the prepared open tubular column and synthesized gold nanoparticles. By comparing different coating times of gold nanoparticles and thiols β-cyclodextrin, we got the optimal conditions for preparing the open tubular column. Also, the separation parameters were optimized including buffer pH, buffer concentration and applied voltage. Separation effectiveness of open tubular column was verified by the separation of four pairs of drug enantiomers including bifonazole, fexofenadine, omeprazole and lansoprazole, and satisfactory separation results were achieved for these analytes studied. In addition, the column showed good stability and repeatability. The relative standard deviation values less than 5% were obtained through intra-day, inter-day, and column-to-column investigations. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Combinatorial treatment of DNA and chromatin-modifying drugs cause cell death in human and canine osteosarcoma cell lines.

    Directory of Open Access Journals (Sweden)

    Venugopal Thayanithy

    Full Text Available Downregulation of microRNAs (miRNAs at the 14q32 locus stabilizes the expression of cMYC, thus significantly contributing to osteosarcoma (OS pathobiology. Here, we show that downregulation of 14q32 miRNAs is epigenetically regulated. The predicted promoter regions of miRNA clusters at 14q32 locus showed no recurrent patterns of differential methylation, but Saos2 cells showed elevated histone deacetylase (HDAC activity. Treatment with 4-phenylbutyrate increased acetylation of histones associated with 14q32 miRNAs, but interestingly, robust restoration of 14q32 miRNA expression, attenuation of cMYC expression, and induction of apoptosis required concomitant treatment with 5-Azacytidine, an inhibitor of DNA methylation. These events were associated with genome-wide gene expression changes including induction of pro-apoptotic genes and downregulation of cell cycle genes. Comparable effects were achieved in human and canine OS cells using the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat and the DNA methylation inhibitor Zebularine (Zeb, with significantly more pronounced cytotoxicity in cells whose molecular phenotypes were indicative of aggressive biological behavior. These results suggested that the combination of these chromatin-modifying drugs may be a useful adjuvant in the treatment of rapidly progressive OS.

  1. The effective encapsulation of a hydrophobic lipid-insoluble drug in solid lipid nanoparticles using a modified double emulsion solvent evaporation method.

    Science.gov (United States)

    Nabi-Meibodi, Mohsen; Vatanara, Alireza; Najafabadi, Abdolhossein Rouholamini; Rouini, Mohammad Reza; Ramezani, Vahid; Gilani, Kambiz; Etemadzadeh, Seyed Mohammad Hossein; Azadmanesh, Kayhan

    2013-12-01

    Raloxifene HCl (RH), a selective estrogen receptor modulator (SERM), is indicated for the prophylaxis or treatment of postmenopausal osteoporosis. RH shows extremely poor bioavailability due to limited solubility and an extensive intestinal/hepatic first-pass metabolism. Solid lipid nanoparticles (SLNs) are valuable carriers that can enhance drug bioavailability. However, in the case of RH, the encapsulation of the drug in SLNs remains a challenge because of its poor solubility in both water and lipids. In this study, a series of RH-containing SLNs (RH-SLNs) were generated using a modified double emulsion solvent evaporation (DESE) method. Briefly, RH with various drug/lipid ratios was solubilized in the inner core of a double emulsion using different water/organic solvent mixtures. Our best formulation was achieved with the formation of negatively charged nanoparticles, 180nm in diameter, with an encapsulation and loading efficiency of 85% and 4.5%, respectively. It also showed a Fickian mechanism of the drug release in the basic dissolution media. Thermal analysis revealed a distinct decrease in the crystallinity of lipids and RH in comparison with the unprocessed materials. The results of a cell viability assay also showed a better antiproliferative effect of the drug-loaded SLNs versus the free drug solution. Thus, these results indicated that the modified DESE method could be proposed for the effective encapsulation of RH in SLNs with appropriate physicochemical and biological properties. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Risk of Subsequent Infection Among Patients Receiving Tumor Necrosis Factor Inhibitors and Other Disease-Modifying Antirheumatic Drugs.

    Science.gov (United States)

    Accortt, Neil A; Bonafede, Machaon M; Collier, David H; Iles, Jan; Curtis, Jeffrey R

    2016-01-01

    To describe the incidence of subsequent serious infections in patients who received systemic drug therapy after an initial serious infection. Patients with rheumatic conditions (rheumatoid arthritis [RA], psoriatic arthritis, ankylosing spondylitis) or psoriasis who experienced a serious infection between January 1, 2006 and December 31, 2011 were identified in a claims database. Patients were required to be continuously enrolled in the Truven Health Analytics MarketScan Research Database for 12 months prior to and at least 60 days after the date of discharge or the end of intravenous antibiotic therapy for the index serious infection. Subsequent serious infection incidence rates per 100 patient-years with 95% confidence intervals (95% CIs) were calculated for up to 18 months post-index, starting 60 days post-index. Cox proportional hazards models were used to adjust for baseline demographic and clinical characteristics, treatment duration, and changes during followup. Among the 21,699 patients who met the inclusion criteria, the majority (84.3%) had RA. Patients who received tumor necrosis factor (TNF) inhibitor therapy after their index infection had a lower rate of subsequent serious infections (18.1 per 100 patient-years for those treated with a TNF inhibitor alone and 17.3 per 100 patient-years for those treated with a TNF inhibitor plus a nonbiologic disease-modifying antirheumatic drug [DMARD]) compared with those treated with a nonbiologic DMARD alone (21.4 per 100 patient-years). Etanercept, either alone (adjusted hazard ratio [HR] 0.87, 95% CI 0.77-0.99) or in combination with a nonbiologic DMARD (adjusted HR 0.76, 95% CI 0.66-0.88), and infliximab (only in combination with a nonbiologic DMARD) (adjusted HR 0.80, 95% CI 0.67-0.95) were associated with a significantly lower risk of subsequent serious infections compared with a nonbiologic DMARD alone. We did not observe an increased risk of subsequent infection in patients who received TNF inhibitor

  3. Comparison of Biologic Disease-Modifying Antirheumatic Drug Therapy Persistence Between Biologics Among Rheumatoid Arthritis Patients Switching from Another Biologic.

    Science.gov (United States)

    Johnston, Stephen S; McMorrow, Donna; Farr, Amanda M; Juneau, Paul; Ogale, Sarika

    2015-06-01

    To compare biologic disease-modifying antirheumatic drug therapy persistence between biologics among patients with rheumatoid arthritis (RA) who previously used ≥1 other biologic. Using a large United States administrative claims dataset, we identified adult patients with RA initiating abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, or tocilizumab between January 1, 2010 and January 1, 2012 (initiation date = index). Patients were required to have used ≥1 other biologic before index. Outcomes were biologic persistence, defined in two alternative ways: (1) time from initiation until switching to a different biologic (time to switch) and (2) time from initiation until switching or the first occurrence of a 90-day gap in treatment with the initiated biologic (time to switch/discontinuation). Rituximab was excluded from analyses due to retreatment based on clinical evaluation, which complicates the measurement of persistence. Multivariable survival analyses compared persistence outcomes between tocilizumab and the other biologics, adjusting for patient characteristics. The sample comprised 9,782 biologic initiations; mean age 54 years and 82% female. Compared with tocilizumab, the hazards of switching biologic therapy were significantly higher for abatacept [hazard ratio (HR) = 1.19, P = 0.041], adalimumab (HR = 1.39, P biologic therapy were significantly higher for adalimumab (HR = 1.16, P = 0.014) and certolizumab (HR = 1.15, P biologic persistence to focus specifically on patients with RA who are not naïve to biologic treatment. Among patients with RA who previously used ≥1 other biologic, tocilizumab-treated patients had similar or significantly better biologic persistence compared with other biologics.

  4. [Acupuncture Therapy versus Disease-modifying Antirheumatic Drugs for the Treatment of Ankylosing Spondylitis--a Meta-analysis].

    Science.gov (United States)

    Lv, Zheng-tao; Zhou, Xiang; Chen, An-min

    2015-01-01

    We conducted a meta-analysis evaluating the efficacy and safety of acupuncture compared to disease-modifying antirheumatic drugs in patients with ankylosing spondylitis. Four databases including Pubmed, EMBASE, Cochrane library, and ISI Web of Science were searched in December 2014, taking also the reference section into account. Randomized controlled trials that aimed to assess the efficacy of acupuncture therapy were identified. The inclusion criteria for the outcome measurements were the clinical effect, ESR, occipital wall test, chest expansion, CRP and finger ground distance. Finally, six studies met these inclusion criteria. Two reviewers screened each article independently and were blinded to the findings of each other. We analyzed data from 6 RCTs involving 541 participants. Acupuncture therapy could further improve the clinical effect (OR = 3.01; 95% CI, 1.48-6.13; P = 0.002) and reduce ESR level (SMD = -0.77; 95% CI, -1.46 to -0.08; P = 0.03) compared to DMARDs; a combination of acupuncture and DMARDs could further improve clinical effect (OR = 3.20, 95% CI, 1.36-7.54; P = 0.008), occipital-wall distance (SMD = -0.84; 95% CI, -1.37 to -0.31; P = 0.002), chest expansion (SMD = 0.38; 95% CI, 0.16-0.60; P = 0.0009), and finger-ground distance (SMD = -0.48; 95% CI, -0.87 to -0.09; P = 0.02) as compared to DMARDs treatment alone. Our findings support that acupuncture therapy could be an option to relieve symptoms associated with AS. These results should be interpreted cautiously due to the generally poor methodological qualities of the included trials. © 2015 S. Karger GmbH, Freiburg.

  5. Validating the Modified Drug Adherence Work-Up (M-DRAW Tool to Identify and Address Barriers to Medication Adherence

    Directory of Open Access Journals (Sweden)

    Sun Lee

    2017-09-01

    Full Text Available Barriers to medication adherence stem from multiple factors. An effective and convenient tool is needed to identify these barriers so that clinicians can provide a tailored, patient-centered consultation with patients. The Modified Drug Adherence Work-up Tool (M-DRAW was developed as a 13-item checklist questionnaire to identify barriers to medication adherence. The response scale was a 4-point Likert scale of frequency of occurrence (1 = never to 4 = often. The checklist was accompanied by a GUIDE that provided corresponding motivational interview-based intervention strategies for each identified barrier. The current pilot study examined the psychometric properties of the M-DRAW checklist (reliability, responsiveness and discriminant validity in patients taking one or more prescription medication(s for chronic conditions. A cross-sectional sample of 26 patients was recruited between December 2015 and March 2016 at an academic medical center pharmacy in Southern California. A priming question that assessed self-reported adherence was used to separate participants into the control group of 17 “adherers” (65.4%, and into the intervention group of nine “unintentional and intentional non-adherers” (34.6%. Comparable baseline characteristics were observed between the two groups. The M-DRAW checklist showed acceptable reliability (13 item; alpha = 0.74 for identifying factors and barriers leading to medication non-adherence. Discriminant validity of the tool and the priming question was established by the four-fold number of barriers to adherence identified within the self-selected intervention group compared to the control group (4.4 versus 1.2 barriers, p < 0.05. The current study did not investigate construct validity due to small sample size and challenges on follow-up with patients. Future testing of the tool will include construct validation.

  6. Fe3O4nanoparticles modified by CD-containing star polymer for MRI and drug delivery.

    Science.gov (United States)

    Cha, Ruitao; Li, Juanjuan; Liu, Yang; Zhang, Yifan; Xie, Qian; Zhang, Mingming

    2017-10-01

    Fe 3 O 4 nanoparticles with ultrasmall sizes show good T 1 or T 1 +T 2 contrast abilities, and have attracted considerable interest in the field of magnetic resonance imaging (MRI) contrast agents. For effective biomedical applications, the colloidal stability and biocompatibility of the Fe 3 O 4 nanoparticles need to be improved without reducing MRI relaxivity. In this paper, star polymers were used as coating materials to modify Fe 3 O 4 nanoparticles in view of their dense molecular architecture with moderate flexibility. The star polymer was composed of a β-cyclodextrin (β-CD) core and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) arms. Meanwhile, reduced glutathione (GSH), as a model drug, was also associated with the star polymer. Thus, a new platform for simultaneous diagnosis and treatment was achieved. Compared to the Fe 3 O 4 nanoparticles coated with linear polymers, the Fe 3 O 4 nanoparticles coated with star polymers (Fe 3 O 4 @GCP) possessed higher GSH association capacity and better stability in serum-containing solution. GSH could be released from Fe 3 O 4 @GCP nanoparticles in response to pH value of the solution. Since the sulfhydryl group on GSH is able to combine free radicals, Fe 3 O 4 @GCP nanoparticles exhibited less cytotoxicity compared to the Fe 3 O 4 nanoparticles without including GSH. Furthermore, the nanoparticles could also serve as good T 1 MRI contrast agent, and the MRI relaxivity of Fe 3 O 4 @GCP nanoparticles did not decrease after coated with the star polymer. These results indicate that the precisely designed Fe 3 O 4 @GCP nanoparticles could be used as a versatile promising theranostic nano-platform. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Use of Disease-modifying Antirheumatic Drugs for Inflammatory Arthritis in US Veterans: Effect of Specialty Care and Geographic Distance.

    Science.gov (United States)

    Walsh, Jessica A; Pei, Shaobo; Burningham, Zachary; Penmetsa, Gopi; Cannon, Grant W; Clegg, Daniel O; Sauer, Brian C

    2018-03-01

    To evaluate the effect of access to and distance from rheumatology care on the use of disease-modifying antirheumatic drugs (DMARD) in US veterans with inflammatory arthritis (IA). Provider encounters and DMARD dispensations for IA (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) were evaluated in national Veterans Affairs (VA) datasets between January 1, 2015, and December 31, 2015. Among 12,589 veterans with IA, 23.5% saw a rheumatology provider. In the general IA population, 25.3% and 13.6% of veterans were exposed to a synthetic DMARD (sDMARD) and biologic DMARD (bDMARD), respectively. DMARD exposure was 2.6- to 3.4-fold higher in the subpopulation using rheumatology providers, compared to the general IA population. The distance between veterans' homes and the closest VA rheumatology site was < 40 miles (Near) for 55.9%, 40-99 miles (Intermediate) for 31.7%, and ≥ 100 miles (Far) for 12.4%. Veterans in the Intermediate and Far groups were less likely to see a rheumatology provider than veterans in the Near group (RR = 0.72 and RR = 0.49, respectively). Exposure to bDMARD was 34% less frequent in the Far group than the Near group. In the subpopulation who used rheumatology care, the bDMARD exposure discrepancy did not persist between distance groups. Use of rheumatology care and DMARD was low for veterans with IA. DMARD exposure was strongly associated with rheumatology care use. Veterans in the general IA population living far from rheumatology sites accessed rheumatology care and bDMARD less frequently than veterans living close to rheumatology sites.

  8. Fast Removal of Citalopram Drug from Waste Water Using Magnetic Nanoparticles Modified with Sodium Dodecyl Sulfate Followed by UV-Spectrometry

    Directory of Open Access Journals (Sweden)

    M. Khoeini Sharifabadi

    2014-02-01

    Full Text Available A simple and sensitive, solid-phase extraction method for the removal of Citalopram drug from waste water has been developed by using magnetic nanoparticles modified with surfactant sodium dodecyl sulfate. These magnetic nanoparticles have shown great adsorptive tendency towards Citalopram drug. The effect of different parameters influencing the extraction efficiency of this drug were investigated and optimized including the pH, amount of the surfactant, contact time and temperature. The extracts were analyzed by ultraviolet spectrophotometry at 239nm. Under these conditions, the related standard deviation (RSD % of the method at two concentrations (5 and 50µg.mL-1 was in the range of (3.14–3.75 % (n = 8. The calibration curve was linear in the range of 2-100 µg.mL-1 of Citalopram drug with a correlation coefficient of >0.99.

  9. Fast Removal of Citalopram Drug from Waste Water Using Magnetic Nanoparticles Modified with Sodium Dodecyl Sulfate Followed by UV-Spectrometry

    Directory of Open Access Journals (Sweden)

    M. Khoeini Sharifabadi

    2013-04-01

    Full Text Available A simple and sensitive, solid-phase extraction method for the removal of Citalopram drug from waste water has been developed by using magnetic nanoparticles modified with surfactant sodium dodecyl sulfate. These magnetic nanoparticles have shown great adsorptive tendency towards Citalopram drug. The effect of different parameters influencing the extraction efficiency of this drug were investigated and optimized including the pH, amount of the surfactant, contact time and temperature. The extracts were analyzed by ultraviolet spectrophotometry at 239nm. Under these conditions, the related standard deviation (RSD % of the method at two concentrations (5 and 50µg.mL-1 was in the range of (3.14–3.75 % (n = 8. The calibration curve was linear in the range of 2-100 µg.mL-1 of Citalopram drug with a correlation coefficient of >0.99.

  10. Electro-oxidation of some non-steroidal anti-inflammatory drugs on an alumina nanoparticle-modified glassy carbon electrode

    OpenAIRE

    TABESHNIA, Mahla; HELI, Hossein; JABBARI, Ali

    2010-01-01

    The electro-oxidation of mefenamic acid, diclofenac, and indomethacin on glassy carbon and alumina nanoparticle-modified glassy carbon electrodes in a phosphate buffer solution at physiological pH was studied. The techniques of cyclic voltammetry, chronoamperometry, impedance spectroscopy, and steady state polarization measurements were applied. The drugs were irreversibly oxidized on bath electrodes via an anodic peak and the process was controlled by diffusion in the bulk of soluti...

  11. Factors associated with initial or subsequent choice of biologic disease-modifying antirheumatic drugs for treatment of rheumatoid arthritis.

    Science.gov (United States)

    Jin, Yinzhu; Desai, Rishi J; Liu, Jun; Choi, Nam-Kyong; Kim, Seoyoung C

    2017-07-05

    Biologic disease-modifying antirheumatic drugs (DMARDs) are increasingly used for rheumatoid arthritis (RA) treatment. However, little is known based on contemporary data about the factors associated with DMARDs and patterns of use of biologic DMARDs for initial and subsequent RA treatment. We conducted an observational cohort study using claims data from a commercial health plan (2004-2013) and Medicaid (2000-2010) in three study groups: patients with early untreated RA who were naïve to any type of DMARD and patients with prevalent RA with or without prior exposure to one biologic DMARD. Multivariable logistic regression models were used to examine the effect of patient demographics, clinical characteristics and healthcare utilization factors on the initial and subsequent choice of biologic DMARDs for RA. We identified a total of 195,433 RA patients including 78,667 (40%) with early untreated RA and 93,534 (48%) and 23,232 (12%) with prevalent RA, without or with prior biologic DMARD treatment, respectively. Patients in the commercial insurance were 87% more likely to initiate a biologic DMARD versus patients in Medicaid (OR = 1.87, 95% CI = 1.70-2.05). In Medicaid, African-Americans had lower odds of initiating (OR = 0.59, 95% CI = 0.51-0.68 in early untreated RA; OR = 0.71, 95% CI = 0.61-0.74 in prevalent RA) and switching (OR = 0.71, 95% CI = 0.55-0.90) biologic DMARDs than non-Hispanic whites. Prior use of steroid and non-biologic DMARDs predicted both biologic DMARD initiation and subsequent switching. Etanercept, adalimumab, and infliximab were the most commonly used first-line and second-line biologic DMARDS; patients on anakinra and golimumab were most likely to be switched to other biologic DMARDS. Insurance type, race, and previous use of steroids and non-biologic DMARDs were strongly associated with initial or subsequent treatment with biologic DMARDs.

  12. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update

    Science.gov (United States)

    Smolen, Josef S; Landewé, Robert; Breedveld, Ferdinand C; Buch, Maya; Burmester, Gerd; Dougados, Maxime; Emery, Paul; Gaujoux-Viala, Cécile; Gossec, Laure; Nam, Jackie; Ramiro, Sofia; Winthrop, Kevin; de Wit, Maarten; Aletaha, Daniel; Betteridge, Neil; Bijlsma, Johannes W J; Boers, Maarten; Buttgereit, Frank; Combe, Bernard; Cutolo, Maurizio; Damjanov, Nemanja; Hazes, Johanna M W; Kouloumas, Marios; Kvien, Tore K; Mariette, Xavier; Pavelka, Karel; van Riel, Piet L C M; Rubbert-Roth, Andrea; Scholte-Voshaar, Marieke; Scott, David L; Sokka-Isler, Tuulikki; Wong, John B; van der Heijde, Désirée

    2014-01-01

    In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least

  13. [Side-effects of the treatment with disease modifying drugs in patients with multiple sclerosis: an analysis of register data in the Yaroslavl region].

    Science.gov (United States)

    Spirin, N N; Kasatkin, D S; Stepanov, I O; Shipova, E G; Baranova, N S

    2012-01-01

    Authors have followed up 230 patients with multiple sclerosis treated with disease modifying drugs (DMD) using the data of the Multiple sclerosis register of the Yaroslavl oblast during 2009-2011. Original drugs and their generics registered in Russia are used. Patients received interferon-beta 1a for intramuscular introduction (avonex - 3.0%), interferon-beta 1a for hypodermic injection (rebif - 19.2%, genfakson - 8.5%), interferon-beta 1b (betaferon - 16.5%, extavia - 18.2%, ronbetal - 18.0%), glatimer acetate (copaxone - 16.7%). Adverse effects were recorded and subjective tolerability of the drug by the patient was assessed. Statistically significant differences in the safety profile between some bioanalogues and original DMD were identified. This finding suggests that effects of different DMD should be studied in depth in clinical and post marketing trials.

  14. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial.

    Science.gov (United States)

    Scott, David L; Ibrahim, Fowzia; Farewell, Vern; O'Keeffe, Aidan G; Walker, David; Kelly, Clive; Birrell, Fraser; Chakravarty, Kuntal; Maddison, Peter; Heslin, Margaret; Patel, Anita; Kingsley, Gabrielle H

    2015-03-13

    To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs. Open label pragmatic randomised multicentre two arm non-inferiority trial over 12 months. 24 rheumatology clinics in England. Patients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy. Biologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for non-responders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders. reduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy. quality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data. 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of -0.30 with the tumour necrosis factor inhibitor strategy and -0.45 with the alternative combined drug strategy. The difference between

  15. Enhancement of the predicted drug hepatotoxicity in gel entrapped hepatocytes within polysulfone-g-poly (ethylene glycol) modified hollow fiber

    International Nuclear Information System (INIS)

    Shen Chong; Zhang Guoliang; Meng Qin

    2010-01-01

    Collagen gel-based 3D cultures of hepatocytes have been proposed for evaluation of drug hepatotoxicity because of their more reliability than traditional monolayer culture. The collagen gel entrapment of hepatocytes in hollow fibers has been proven to well reflect the drug hepatotoxicity in vivo but was limited by adsorption of hydrophobic drugs onto hollow fibers. This study aimed to investigate the impact of hollow fibers on hepatocyte performance and drug hepatotoxicity. Polysulfone-g-poly (ethylene glycol) (PSf-g-PEG) hollow fiber was fabricated and applied for the first time to suppress the drug adsorption. Then, the impact of hollow fibers was evaluated by detecting the hepatotoxicity of eight selected drugs to gel entrapped hepatocytes within PSf and PSf-g-PEG hollow fibers, or without hollow fibers. The hepatocytes in PSf-g-PEG hollow fiber showed the highest sensitivity to drug hepatotoxicity, while those in PSf hollow fiber and cylindrical gel without hollow fiber underestimated the hepatotoxicity due to either drug adsorption or low hepatic functions. Therefore, the 3D culture of gel entrapped hepatocytes within PSf-g-PEG hollow fiber would be a promising tool for investigation of drug hepatotoxicity in vitro.

  16. A multifunctional β-CD-modified Fe3O4@ZnO:Er3+,Yb3+ nanocarrier for antitumor drug delivery and microwave-triggered drug release

    International Nuclear Information System (INIS)

    Peng, Hongxia; Cui, Bin; Li, Guangming; Wang, Yingsai; Li, Nini; Chang, Zhuguo; Wang, Yaoyu

    2015-01-01

    We constructed a novel core–shell structured Fe 3 O 4 @ZnO:Er 3+ ,Yb 3+ @(β-CD) nanoparticles used as drug carrier to investigate the loading and controllable release properties of the chemotherapeutic drug etoposide (VP-16). The cavity of β-cyclodextrin is chemically inert, it can store etoposide molecules by means of hydrophobic interactions. The Fe 3 O 4 core and ZnO:Er 3+ ,Yb 3+ shell functioned successfully for magnetic targeting and up-conversion fluorescence imaging, respectively. In addition, the ZnO:Er 3+ ,Yb 3+ shell acts as a good microwave absorber with excellent microwave thermal response property for microwave triggered drug release (the VP-16 release of 18% under microwave irradiation for 15 min outclass the 2% within 6 h without microwave irradiation release). The release profile could be controlled by the duration and number of cycles of microwave application. This material therefore promises to be a useful noninvasive, externally controlled drug-delivery system in cancer therapy. - Graphical abstract: We functionalized a multifunctional core–shell Fe 3 O 4 @ZnO:Er 3+ ,Yb 3+ nanocarriers by adding β-cyclodextrin, which is capable of carrying drug molecules and triggered release of the drug by microwave treatment. - Highlights: • We constructed Fe 3 O 4 @ZnO:Er 3+ ,Yb 3+ @(β-CD) nanoparticles used as a drug carrier. • The nanoparticles have magnetic and up-conversion fluorescence properties. • The nanoparticles have excellent microwave thermal response property. • The nanocomposite could be a controllable drug release triggered by microwave

  17. Factors associated with the initiation of biologic disease-modifying antirheumatic drugs in Texas Medicaid patients with rheumatoid arthritis.

    Science.gov (United States)

    Kim, Gilwan; Barner, Jamie C; Rascati, Karen; Richards, Kristin

    2015-05-01

    Rheumatoid arthritis (RA) is a progressive autoimmune disorder of joints that is associated with high health care costs, yet guidance is lacking on how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs), a class of medications that is the major cost driver in RA management. Few studies have examined the factors associated with the transition from nonbiologic DMARDs, the first-line therapy for RA, to biologic DMARDs in RA patients.  To examine patient sociodemographics, medication use patterns, and clinical characteristics associated with initiation of biologic DMARDs.   This was a retrospective study using the Texas Medicaid prescription and medical claims database from July 1, 2003-December 31, 2010. Adults (aged 18-63 years) with an RA diagnosis (ICD-9-CM code 714.xx), no nonbiologic DMARD or biologic DMARD use during the 6-month pre-index period, and a minimum of 2 prescription claims for the same nonbiologic DMARD during the post-index period were included in the study. The index date was defined as the date when the first nonbiologic DMARD claim was made. Predictors of initiation of biologic DMARDs were age, gender, race, adherence (proportion of days covered), persistence to nonbiologic DMARDs, comorbidity (Charlson Comorbidity Index [CCI]), pain medication use, glucocorticoid use, and rheumatologist visit. Logistic regression was used to examine the factors associated with the initiation of biologic DMARDs.   A total of 2,714 patients were included. After controlling for patient characteristics, logistic regression showed, that compared with methotrexate (MTX) users, sulfasalazine (SSZ) and hydroxychloroquine (HCQ) users were less likely to initiate biologic DMARDs by 69.0% (OR = 0.310, 95% CI = 0.221-0.434, P  less than  0.0001) and 79.9% (OR = 0.201, 95% CI = 0.152-0.265, P  less than  0.0001), respectively. Nonbiologic DMARD dual therapy users were 39.1% less likely to initiate biologic DMARDs compared

  18. Integrating sol-gel with cold plasmas modified porous polycaprolactone membranes for the drug-release of silver-sulfadiazine and ketoprofen

    Energy Technology Data Exchange (ETDEWEB)

    Mangindaan, Dave; Chen, Chao-Ting [Department of Chemical Engineering, National Taiwan University of Science and Technology, 43, Keelung Rd., Sec. 4, Taipei 106, Taiwan (China); Wang, Meng-Jiy, E-mail: mjwang@mail.ntust.edu.tw [Department of Chemical Engineering, National Taiwan University of Science and Technology, 43, Keelung Rd., Sec. 4, Taipei 106, Taiwan (China)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer Integrated control-release system of sol-gel and biodegradable polycaprolactone membrane. Black-Right-Pointing-Pointer Biocompatible and nontoxic chitosan-SiO{sub 2} sol-gel for drug loading. Black-Right-Pointing-Pointer Characterizations of the oxygen plasma modified biodegradable PCL porous membrane. Black-Right-Pointing-Pointer Achieved controllable in vitro release for ketoprofen and silver sulfadiazine. Black-Right-Pointing-Pointer The sol-gel/plasma modified porous membranes showed excellent biocompatibility. - Abstract: A controlled release system composed of surface modified porous polycaprolactone (PCL) membranes combined with a layer of tetraorthosilicate (TEOS)-chitosan sol-gel was reported in this study. PCL is a hydrophobic, semi-crystalline, and biodegradable polymer with a relatively slow degradation rate. The drugs chosen for release experiments were silver-sulfadiazine (AgSD) and ketoprofen which were impregnated in the TEOS-chitosan sol-gel. The surface modification was achieved by O{sub 2} plasma and the surfaces were characterized by water contact angle (WCA) measurements, atomic force microscope (AFM), scanning electron microscope and electron spectroscopy for chemical analysis (ESCA). The results showed that the release of AgSD on O{sub 2} plasma treated porous PCL membranes was prolonged when compared with the pristine sample. On the contrary, the release rate of ketoprofen revealed no significant difference on pristine and plasma treated PCL membranes. The prepared PCL membranes showed good biocompatibility for the wound dressing biomaterial applications.

  19. Development of a modified - solid dispersion in an uncommon approach of melting method facilitating properties of a swellable polymer to enhance drug dissolution.

    Science.gov (United States)

    Nguyen, Tuong Ngoc-Gia; Tran, Phuong Ha-Lien; Tran, Thanh Van; Vo, Toi Van; Truong-DinhTran, Thao

    2015-04-30

    The study aimed to develop a modified-solid dispersion method using a swellable hydrophilic polymers accompanied by a conventional carrier to enhance the dissolution of a drug that possesses poor water solubility. Two swellable polymers (hydroxypropyl methylcellulose and polyethylene oxide) were swelled in melted polyethylene glycol 6000 (PEG 6000) in different ratios and under different conditions. The type, amount, and, especially, incorporation method of the swellable polymers were crucial factors affecting the dissolution rate, crystallinity, and molecular interaction of the drug. Interestingly, the method in which the swellable polymer was thoroughly mixed with the melted PEG 6000 as the first step was more effective in increasing drug dissolution than the method in which the drug was introduced to the melted PEG 6000 followed by the addition of the swellable polymer. This system has potential for controlling drug release due to high swelling capabilities of these polymers. Therefore, the current study can be considered to be a promising model for formulations of controlled release systems containing solid dispersions. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. In vitro cytotoxicity and phototoxicity of surface-modified gold nanoparticles associated with neutral red as a potential drug delivery system in phototherapy

    Energy Technology Data Exchange (ETDEWEB)

    Verissimo, Tanira V. [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Laboratory of Photochemistry and Nanobiotechnology, Faculty of Ceilandia, University of Brasilia, Brasilia (Brazil); Santos, Naiara T. [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Silva, Jaqueline R.; Azevedo, Ricardo B. [Institute of Biological Sciences, University of Brasilia, Brasilia (Brazil); Gomes, Anderson J., E-mail: ajgomes@unb.br [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Laboratory of Photochemistry and Nanobiotechnology, Faculty of Ceilandia, University of Brasilia, Brasilia (Brazil); Lunardi, Claure N., E-mail: clunardi@unb.br [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Laboratory of Photochemistry and Nanobiotechnology, Faculty of Ceilandia, University of Brasilia, Brasilia (Brazil)

    2016-08-01

    The surface of gold nanoparticles (AuNP) was modified, improving their interaction with neutral red (NR), by using sodium thioglycolate (TGA) as a covering agent. The resulting NR-AuNPTGA system was evaluated as a potential drug delivery system for photodynamic therapy (PDT). The associations of NR with the gold nanoparticles were evaluated using UV-vis spectrometry and measurement of their zeta potential and size distribution. The toxicity and phototoxicity of NR, AuNPTGA and NR-AuNPTGA were evaluated in NIH-3T3 fibroblast and 4T1 tumor cell lines. The compounds NR and NR-AuNPTGA induced toxicity in 4T1 tumor cells and NIH-3T3 fibroblasts under visible light irradiation. Modification of the surface of AuNP with TGA prevented nanoparticle aggregation and allowed greater association with NR molecules than for naked AuNP. The photosensitizer (PS) characteristics were not affected by its association with the modified surface of the gold nanoparticles, leading to a reduction of cell viability in both cell lines assayed. This NR-AuNPTGA system is a promising drug delivery system for photodynamic cancer therapy. - Highlights: • Modified gold nanoparticle (AuNP) by sodium thioglicolate (TGA) prevents aggregation. • Neutral red (NR) adsorbed on the surface of modified gold nanoparticles (AuNPTGA). • AuNPTGA is suitable as a platform to deliver the NR under irradiation process. • Photodamage of 90% was achieved by NR added to AuNPTGA in 4T1 and NIH-3T3 cells.

  1. Evaluation of coat uniformity and taste-masking efficiency of irregular-shaped drug particles coated in a modified tangential spray fluidized bed processor.

    Science.gov (United States)

    Xu, Min; Heng, Paul Wan Sia; Liew, Celine Valeria

    2015-01-01

    To explore the feasibility of coating irregular-shaped drug particles in a modified tangential spray fluidized bed processor (FS processor) and evaluate the coated particles for their coat uniformity and taste-masking efficiency. Paracetamol particles were coated to 20%, w/w weight gain using a taste-masking polymer insoluble in neutral and basic pH but soluble in acidic pH. In-process samples (5, 10 and 15%, w/w coat) and the resultant coated particles (20%, w/w coat) were collected to monitor the changes in their physicochemical attributes. After coating to 20%, w/w coat weight gain, the usable yield was 81% with minimal agglomeration (processor shows promise for direct coating of irregular-shaped drug particles with wide size distribution. The coated particles with 15% coat were sufficiently taste masked and could be useful for further application in orally disintegrating tablet platforms.

  2. Polymer coating of carrier excipients modify aerosol performance of adhered drugs used in dry powder inhalation therapy.

    Science.gov (United States)

    Traini, Daniela; Scalia, Santo; Adi, Handoko; Marangoni, Elisabetta; Young, Paul M

    2012-11-15

    The potential of excipient coating to enhance aerosol performance of micronized drugs in carrier excipient-drug blends, used in dry powder inhalers, was investigated. Both EC (ethyl cellulose) and PVP (polyvinylpyrrolidone) were used as coating agents. Carriers were prepared via sieve fractioning followed by spray drying, with and without polymer additive. Each uncoated and coated carrier salbutamol sulphate (SS) blended systems were evaluated for particle size, morphology, drug carrier adhesion and aerosolisation performance, after blending and storage for 24h. All carrier-based systems prepared had similar particle sizes and morphologies. The surface chemistries of the carriers were significantly different, as was drug-carrier adhesion and aerosolisation performance. Particle adhesion between SS and aerosol performance (fine particle fraction; FPF) followed the rank: PVP coated>un-coated>EC coated lactose. This rank order could be attributed to the surface energy measured by contact goniometry and related to the chemistry of lactose and each polymer. Storage did not significantly affect aerosol performance, however a rank increase in mean FPF value was observed for uncoated and EC coated lactose. Finally, the net electrostatic charge across the aerosol cloud indicated that the EC coated lactose transferred less charge to SS particles. The performance of each carrier system could be attributed to the carrier surface chemistry and, in general, by careful selection of the coating polymer, drug-carrier adhesion, electrostatic charge and aerosol performance could be controlled. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. A Target-Directed Chemo-Photothermal System Based on Transferrin and Copolymer-Modified MoS2Nanoplates with pH-Activated Drug Release.

    Science.gov (United States)

    Zhang, Aitang; Li, Aihua; Tian, Wenxue; Li, Zichao; Wei, Chen; Sun, Yong; Zhao, Wei; Liu, Mengli; Liu, Jingquan

    2017-08-22

    Molybdenum disulfide (MoS 2 ) nanosheets have attracted significant attention due to their photothermal properties, but the poor solubility and colloidal stability limited their further application in biomedical field. Here, we report a targeted photothermal controllable nanocarrier consisting of MoS 2 nanosheets modified with block copolymer P(OEG-A)-b-P(VBA-co-KH570) and targeting ligand transferrin. P(OEG-A)-b-P(VBA-co-KH570) is synthesized by RAFT polymerization and utilized not only to improve the solubility of MoS 2 nanosheets but also efficiently load the anti-cancer drug doxorubicin (DOX) through an acid-cleavable Schiff base linker. Thiol-functionalized transferrin (Tf-SH) is anchored onto the surface of MoS 2 nanosheets by the formation of disulfide bonds, which could further enhance the cellular uptake of DOX and MoS 2 to HepG2 cells for high-efficiency synergetic therapy. The drug release experiments exhibited the minimal release of DOX at room temperature and neutral pH, and the maximal drug release of 53 % at acidic tumor pH and hyperthermia condition after 48 h. In addition, the DOX-loaded, Tf-SH and P(OEG-A)-b-P(VBA-co-KH570) modified MoS 2 (DOX-POVK-MoS 2 -Tf) showed better a therapeutic effect than DOX-POVK-MoS 2 and POVK-MoS 2 , probably owing to the combined effects of target-directed uptake, acid-triggered drug release, and NIR induced localized heating, which suggest the designed MoS 2 nanocarriers are promising for applications in multi-modal cancer therapy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Modified human serum albumins as carriers for the specific delivery of antiviral drugs to liver- and blood cells

    NARCIS (Netherlands)

    Jansen, Robert Walter

    1992-01-01

    The general goal of this study, was to determine the possibility of a targeted delivery of antiviral drugs to their site of action. We decided to focus on two viral diseases; HIV and Hepatitis B, that replicate in T,-lymphocytes, monocytes/macrophages and hepatocytes respectively. The specific aims

  5. Double-layered hyaluronic acid/stearic acid-modified polyethyleneimine nanoparticles encapsulating (-)-gossypol: a nanocarrier for chiral anticancer drugs

    OpenAIRE

    Liu, Hao; Li, Ke; Lan, Lan; Ma, Jingwen; Zeng, Yun; Xu, Liang; Wu, Daocheng

    2014-01-01

    This study aimed to enhance the water solubility and antitumor efficacy of (-)-gossypol. Polyethyleneimine conjugated with stearic acid (PgS) was used for loading and protecting (-)-gossypol through hydrogen bonding. Double-layered hyaluronic acid (HA)-modified PgS nanoparticles encapsulating (-)-gossypol [(-)-G-PgSHAs] were prepared through a two-step fabrication process. The nanoparticles possessed a uniform spherical shape with a dynamic size of 110.9 ± 2.4 nm, which was determined through...

  6. Ionic Liquid Crystals Modifier for Selective Determination of Terazosin Antihypertensive Drug in Presence of Common Interference Compounds

    Directory of Open Access Journals (Sweden)

    Nada F. Atta

    2017-01-01

    Full Text Available Electrochemical sensor was fabricated based on carbon paste electrode modified with an ionic liquid crystal ILC (2-chloro-1,3-dimethyl-imidazolidinium hexafluorophosphate in presence of sodium dodecyl sulfate for the selective electrochemical determination of Terazosin (TZ in presence of common interference compounds. The electrode performance was compared in presence of other ionic liquids ILs (1-Butyl-4-methyl pyridinium tetrafluoroborate and (1-n-Hexyl-3-methyl imidazolium tetrafluoroborate. Ultrasensitive determination of Terazosin HCl at the ILC modified electrode in the linear dynamic ranges of 0.002 to 0.09 μmol·L−1 and 0.2 to 30 μmol·L−1 with correlation coefficients 0.996 and 0.995 and LODs 1.69 × 10−11 mol·L−1 and 6.43 × 10−9 mol·L−1, respectively, were obtained. Selective determination of TZ in presence of uric acid and ascorbic acid and simultaneous determination of binary mixtures of TZ/dopamine, TZ/paracetamol and TZ/Morphine were also determined successfully using the modified sensor.

  7. Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

    Directory of Open Access Journals (Sweden)

    Yan X

    2018-01-01

    Full Text Available Xiuju Yan,1,* Lixiao Xu,1,* Chenchen Bi,1 Dongyu Duan,1 Liuxiang Chu,1 Xin Yu,1 Zimei Wu,1 Aiping Wang,1,2 Kaoxiang Sun1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University, Ministry of Education, Yantai University, Yantai, Shandong Province, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People’s Republic of China *These authors contributed equally to this work Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD. Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD.Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs.Results: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05 in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf

  8. Use and Spending for Biologic Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis Among US Medicare Beneficiaries.

    Science.gov (United States)

    Yazdany, Jinoos; Tonner, Chris; Schmajuk, Gabriela

    2015-09-01

    Biologic therapies have assumed an important role in treating rheumatoid arthritis (RA). We sought to investigate use, spending, and patient cost-sharing for Medicare beneficiaries using biologic drugs for RA, comparing patients exposed to minimal cost-sharing because of a Part D low-income subsidy (LIS) to those facing substantial out-of-pocket costs (OOP). We performed a retrospective, nationwide study using 2009 Medicare claims for a 5% random sample of beneficiaries with RA who had at least 1 RA drug dispensed. We analyzed biologic drug utilization and costs across the Part B (medical benefit) and Part D (pharmacy benefit) programs by LIS status using multinomial regression. We also projected OOP costs as the Affordable Care Act (ACA) mandates closure of the Part D coverage gap by 2020. Among 6,932 beneficiaries, 1,812 (26.1%) received a biologic drug. LIS beneficiaries were significantly more likely to obtain Part D home-administered biologics (relative risk ratio [RRR] 2.98, 95% confidence interval [95% CI] 2.50-3.56), while non-LIS beneficiaries were less likely to receive Part D biologic agents (RRR 0.58, 95% CI 0.48-0.69). OOP costs in Part D were lower, as expected, for LIS beneficiaries ($72 versus $3,751 per year for non-LIS). Non-LIS beneficiaries had lower costs for Part B facility-administered biologic agents (range $0-$2,584) than for Part D home-administered biologic agents. ACA reforms will narrow OOP differences between Part D and B for non-LIS beneficiaries. In contrast to LIS beneficiaries who receive mostly Part D home-administered biologic DMARDs, nonsubsidized beneficiaries have significant cost-based incentives to obtain facility-administered biologic DMARDs through Part B. The ACA will result in only slightly lower costs for Part D biologic drugs for these beneficiaries. © 2015, American College of Rheumatology.

  9. Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

    International Nuclear Information System (INIS)

    Balaev, V. V.; Lashkov, A. A.; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M.

    2015-01-01

    Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis (YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability (R work = 16.2, R free = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh

  10. Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

    Energy Technology Data Exchange (ETDEWEB)

    Balaev, V. V.; Lashkov, A. A., E-mail: alashkov83@gmail.com; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2015-03-15

    Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis (YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability (R{sub work} = 16.2, R{sub free} = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh.

  11. Long-term effects of exposure to disease-modifying drugs in the offspring of mothers with multiple sclerosis: a retrospective chart review.

    Science.gov (United States)

    Fragoso, Yara D; Adoni, Tarso; Alves-Leon, Soniza V; Azambuja, Nério D; Barreira, Amilton A; Brooks, Joseph B B; Carneiro, Denise S D; Carvalho, Margarete J; Claudino, Rinaldo; Comini-Frota, Elizabeth R; Domingues, Renan B; Finkelzstejn, Alessandro; Gama, Paulo D; Giacomo, Maria C B; Gomes, Sidney; Goncalves, Marcus V M; Grzesiuk, Anderson K; Kaimen-Maciel, Damacio R; Mendes, Maria F; Morales, Nivea M O; Morales, Rogério R; Muniz, Andre; Papais-Alvarenga, Regina M; Parolin, Monica K F; Ribeiro, Sonia B F; Ruocco, Heloisa H; Siquineli, Fabio; Tosta, Elza D

    2013-11-01

    Multiple sclerosis (MS) mainly affects women of fertile age. To date, the only recommendation for women with MS intending to become pregnant is to stop all treatment. This recommendation reflects the concerns about the effects of disease-modifying drugs (DMDs) on the offspring. The objective of the present study was to assess the potential long-term effects of maternal exposure to DMDs on the offspring. This was a retrospective study revising medical data on the offspring of women with MS. These women now have children aged at least 1 year and include a group of patients that were not exposed to any DMDs for at least 3 months prior to pregnancy and during the whole gestation (control group). Another group of patients had at least 2 weeks of exposure to DMDs, mainly to interferon beta or glatiramer acetate The women with MS participating in this study have children currently aged, on average, 6.6 years (range 1-39 years). There was no pattern of drug-related adverse events or complications in the children whose mothers were exposed to DMDs. No specific long-term adverse events were observed in the offspring of women with MS who were exposed to drugs during pregnancy. The profile of relevant diagnoses in their children was similar to that of children whose mothers had not been exposed to DMDs. The present retrospective study did not show a specific profile of long-term deleterious drug effects on children born from mothers who were exposed to drugs for MS treatment.

  12. Optimization and application of octadecyl-modified monolithic silica for solid-phase extraction of drugs in whole blood samples.

    Science.gov (United States)

    Namera, Akira; Saito, Takeshi; Ota, Shigenori; Miyazaki, Shota; Oikawa, Hiroshi; Murata, Kazuhiro; Nagao, Masataka

    2017-09-29

    Monolithic silica in MonoSpin for solid-phase extraction of drugs from whole blood samples was developed to facilitate high-throughput analysis. Monolithic silica of various pore sizes and octadecyl contents were synthesized, and their effects on recovery rates were evaluated. The silica monolith M18-200 (20μm through-pore size, 10.4nm mesopore size, and 17.3% carbon content) achieved the best recovery of the target analytes in whole blood samples. The extraction proceeded with centrifugal force at 1000rpm for 2min, and the eluate was directly injected into the liquid chromatography-mass spectrometry system without any tedious steps such as evaporation of extraction solvents. Under the optimized condition, low detection limits of 0.5-2.0ngmL -1 and calibration ranges up to 1000ngmL -1 were obtained. The recoveries of the target drugs in the whole blood were 76-108% with relative standard deviation of less than 14.3%. These results indicate that the developed method based on monolithic silica is convenient, highly efficient, and applicable for detecting drugs in whole blood samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy.

    Science.gov (United States)

    Takara, Kazuhiro; Hatakeyama, Hiroto; Kibria, Golam; Ohga, Noritaka; Hida, Kyoko; Harashima, Hideyoshi

    2012-08-20

    Anti-angiogenic therapy is a potential chemotherapeutic strategy for the treatment of drug resistant cancers. However, a method for delivering such drugs to tumor endothelial cells remains to be a major impediment to the success of anti-angiogenesis therapy. We designed liposomes (LPs) with controlled diameter of around 300 nm, and modified them with a specific ligand and a cell penetrating peptide (CPP) (a dual-ligand LP) for targeting CD13-expressing neovasculature in a renal cell carcinoma (RCC). We modified the LPs with an NGR motif peptide on the top of poly(ethylene glycol) and tetra-arginine (R4) on the surface of the liposome membrane as a specific and CPP ligand, respectively. The large size prevented extravasation of the dual-ligand LP, which allowed it to associate with target vasculature. While a single modification with either the specific or CPP ligand showed no increase in targetability, the dual-ligand enhanced the amount of delivered liposomes after systemic administration to OS-RC-2 xenograft mice. The anti-tumor activity of a dual-ligand LP encapsulating doxorubicin was evaluated and the results were compared with Doxil, which is clinically used to target tumor cells. Even though Doxil showed no anti-tumor activity, the dual-ligand LP suppressed tumor growth because the disruption of tumor vessels was efficiently induced. The comparison showed that tumor endothelial cells (TECs) were more sensitive to doxorubicin by 2 orders than RCC tumor cells, and the disruption of tumor vessels was efficiently induced. Collectively, the dual-ligand LP is promising carrier for the treatment of drug resistant RCC via the disruption of TECs. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Captopril-polyethyleneimine conjugate modified gold nanoparticles for co-delivery of drug and gene in anti-angiogenesis breast cancer therapy.

    Science.gov (United States)

    Li, Manhong; Li, Yong; Huang, Xiaohui; Lu, Xizhi

    2015-01-01

    Captopril-polyethyleneimine (CP) containing low molecular weight polyethyleneimine and anti-angiogenesis drug captopril conjugated via an amide bond was fabricated to modify gold nanoparticles and complex with siRNA to construct siRNA/CP/GNP complexes for the co-delivery of drug and siRNA in anti-angiogenesis breast cancer therapy. The self-assembled siRNA/CP/GNP complexes exhibited desirable and homogenous particle size, reasonable positive charges and condensation ability, and effective gene-silencing property in vitro. In addition, siRNA/CP/GNP complexes co-delivering captopril and siRNA achieved combined angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor mRNA and protein via different pathways in vitro, as compared to mono-delivery systems. In vivo investigation on nude mice bearing MDA-MB435 tumor xenografts revealed that siRNA/CP/GNP complexes possessed satisfying tumor homing ability and strong antitumor activity. These findings suggested that siRNA/CP/GNP complexes could be an ideal system for simultaneous transfer of drug and siRNA, which might be a new promising strategy for effective breast cancer therapy.

  15. Dissolution enhancement of a poorly water-soluble antimalarial drug by means of a modified multi-fluid nozzle pilot spray drier

    International Nuclear Information System (INIS)

    Sahoo, Nanda Gopal; Kakran, Mitali; Li Lin; Judeh, Zaher; Mueller, Rainer H.

    2011-01-01

    A spray drier with a modified multi-fluid nozzle was used to prepare microparticles of a poorly water-soluble antimalarial drug, artemisinin (ART), with the aim of improving its dissolution in water. ART was co-spray dried with a hydrophilic polymer, polyethylene glycol (PEG). The differential scanning calorimetry and X-ray diffraction studies showed that the crystallinity of ART decreased after spray drying. Compared to the physical mixture of ART and PEG, the amorphous phase of ART in the spray dried ART-PEG composites increased, which depended on the weight ratio of drug to polymer. The phase-solubility studies revealed that the aqueous solubility of ART was improved by the presence of PEG. The dissolution of ART from the spray dried ART-PEG composites was more rapid than that from their respective physical mixture and the original ART powder. For example, the dissolution of ART from the spray dried ART-PEG composite (1:6) was 6.5 times higher than that from the original ART powder in the first 30 min. In the mathematical modeling, the Weibull and Korsemeyer-Peppas models were found to best fit to the in vitro dissolution data and then the drug release mechanism was considered as the Fickian diffusion.

  16. Dissolution enhancement of a poorly water-soluble antimalarial drug by means of a modified multi-fluid nozzle pilot spray drier

    Energy Technology Data Exchange (ETDEWEB)

    Sahoo, Nanda Gopal; Kakran, Mitali [School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Li Lin, E-mail: mlli@ntu.edu.sg [School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Judeh, Zaher [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459 (Singapore); Mueller, Rainer H. [Free University of Berlin, Department of Pharmacy, Biopharmaceutics and Nutricosmetics, Kelchstrass 31, Berlin (Germany)

    2011-03-12

    A spray drier with a modified multi-fluid nozzle was used to prepare microparticles of a poorly water-soluble antimalarial drug, artemisinin (ART), with the aim of improving its dissolution in water. ART was co-spray dried with a hydrophilic polymer, polyethylene glycol (PEG). The differential scanning calorimetry and X-ray diffraction studies showed that the crystallinity of ART decreased after spray drying. Compared to the physical mixture of ART and PEG, the amorphous phase of ART in the spray dried ART-PEG composites increased, which depended on the weight ratio of drug to polymer. The phase-solubility studies revealed that the aqueous solubility of ART was improved by the presence of PEG. The dissolution of ART from the spray dried ART-PEG composites was more rapid than that from their respective physical mixture and the original ART powder. For example, the dissolution of ART from the spray dried ART-PEG composite (1:6) was 6.5 times higher than that from the original ART powder in the first 30 min. In the mathematical modeling, the Weibull and Korsemeyer-Peppas models were found to best fit to the in vitro dissolution data and then the drug release mechanism was considered as the Fickian diffusion.

  17. Preparation, Characterization and Evaluation of α-Tocopherol Succinate-Modified Dextran Micelles as Potential Drug Carriers

    Directory of Open Access Journals (Sweden)

    Jingmou Yu

    2015-09-01

    Full Text Available In the present study, α-tocopherol succinate (TOS conjugated dextran (Dex-TOS was synthesized and characterized by fourier transform infrared (FT-IR spectroscopy, 1H nuclear magnetic resonance (1H NMR, dynamic light scattering (DLS and fluorescence spectroscopy. Dex-TOS could form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC is 0.0034 mg/mL. Doxorubicin (Dox was selected as a model drug. Dox-loaded Dex-TOS (Dex-TOS/Dox micelles were prepared by a dialysis method. The size of Dex-TOS/Dox micelles increased from 295 to 325 nm with the Dox-loading content increasing from 4.21% to 8.12%. The Dex-TOS/Dox micelles were almost spherical in shape, as determined by transmission electron microscopy (TEM. In vitro release demonstrated that Dox release from the micelles was in a sustained manner for up to 96 h. The cellular uptake of Dex-TOS/Dox micelles in human nasopharyngeal epidermoid carcinoma (KB cells is an endocytic process determined by confocal laser scanning microscopy (CLSM. Moreover, Dex-TOS/Dox micelles exhibited comparable cytotoxicity in contrast with doxorubicin hydrochloride. These results suggested that Dex-TOS micelles could be a promising carrier for drug delivery.

  18. Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yinbo Zhao

    2014-09-01

    Full Text Available In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs modified by Arg–Gly–Asp(RGD peptide, loaded with curcumin (Cur, were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid–mPEG (methoxyl poly(ethylene- glycol, RGD–polyethylene glycol (PEG–cholesterol (Chol copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD–lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD–lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD–lpNPs was increased for human umbilical vein endothelial cells (HUVEC. Furthermore, Cur loaded RGD–lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD–lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD–lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD–lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.

  19. Ethnicity modifies the additive effects of anxiety and drug use disorders on suicidal ideation among black adults in the United States

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2013-01-01

    Full Text Available Background: This study aimed to test if ethnicity moderates the additive effects of lifetime psychiatric disorders on serious suicidal thoughts among a nationally representative sample of Black adults in the United States. Methods: For this study, we used data of 5,181 Black adults (3,570 African Americans and 1,621 Caribbean Blacks who participated in the National Survey of American Life, 2001-2003. Five lifetime psychiatric disorders (i.e., major depressive disorder, general anxiety disorder, post-traumatic stress disorder, alcohol abuse disorder, and drug abuse were considered as the independent variables. Lifetime serious suicidal ideation was considered as the dependent variable. Logistic regressions were used to determine if ethnicity modifies the effects of each psychiatric disorder on serious suicide ideation. Ethnicity was conceptualized as the possible moderator and socio-demographics (i.e., age, gender, education level, employment, marital status and country region were control variables. Results: Among African Americans, major depressive disorder, general anxiety disorder, post-traumatic stress disorder and alcohol abuse disorder were associated with higher odds of suicidal thoughts. Among Caribbean Blacks, major depressive disorder and drug abuse disorder were associated with higher odds of suicidal thoughts. In the pooled sample, there was a significant interaction between ethnicity and anxiety disorder and a marginally significant interaction between ethnicity and drug abuse. Conclusions: Based on our study, suicidality due to psychiatric disorders among Black adults in the United States may depend on ethnicity. General anxiety disorder seems to be a more important risk factor for suicidal ideation among African Americans while drug abuse may contribute more to the risk of suicidal thoughts among Caribbean Blacks.

  20. Extracellular biosynthesis of gadolinium oxide (Gd2O3 nanoparticles, their biodistribution and bioconjugation with the chemically modified anticancer drug taxol

    Directory of Open Access Journals (Sweden)

    Shadab Ali Khan

    2014-03-01

    Full Text Available As a part of our programme to develop nanobioconjugates for the treatment of cancer, we first synthesized extracellular, protein-capped, highly stable and well-dispersed gadolinium oxide (Gd2O3 nanoparticles by using thermophilic fungus Humicola sp. The biodistribution of the nanoparticles in rats was checked by radiolabelling with Tc-99m. Finally, these nanoparticles were bioconjugated with the chemically modified anticancer drug taxol with the aim of characterizing the role of this bioconjugate in the treatment of cancer. The biosynthesized Gd2O3 nanoparticles were characterized by UV–vis spectroscopy, transmission electron microscopy (TEM, X-ray diffraction (XRD and X-ray photoemission spectroscopy (XPS. The Gd2O3–taxol bioconjugate was confirmed by UV–vis spectroscopy and fluorescence microscopy and was purified by using high performance liquid chromatography (HPLC.

  1. Metabolism of a novel side chain modified Δ8(14)-15-ketosterol, a potential cholesterol lowering drug: 28-hydroxylation by CYP27A1

    Science.gov (United States)

    Pettersson, Hanna; Norlina, Maria; Andersson, Ulla; Pikuleva, Irina; Björkhem, Ingemar; Misharin, Alexander Yu.; Wikvall, Kjell

    2009-01-01

    The synthetic inhibitors of sterol biosynthesis, 3β-hydroxy-5α-cholest-8(14)-en-15-one and 3β-hydroxy-24S-methyl-5α-cholesta-8(14),22-dien-15-one, are of interest as potential cholesterol lowering drugs. Rapid metabolism of synthetic 15-ketosterols may lead to a decrease, or loss, of their potency to affect lipid metabolism. 3β-Hydroxy-5α-cholest-8(14)-en-15-one is reported to be rapidly side chain oxygenated by rat liver mitochondria. In an attempt to reduce this metabolism, the novel side-chain modified 15-ketosterol 3β-Hydroxy-24S-methyl-5α-cholesta-8(14),22-dien-15-one was synthesized. We have examined the metabolism by recombinant human CYP27A1 of this novel side-chain modified 3β-hydroxy-24S-methyl-5α-cholesta-8(14),22-dien-15-one and compared the rate of metabolism with that of the previously described 3β-hydroxy-5α-cholest-8(14)-en-15-one. Both sterols were found to be efficiently metabolized by recombinant human CYP27A1. None of the two 15-ketosterols was significantly metabolized by microsomal 7α-hydroxylation. Interestingly, CYP27A1-mediated product formation was much lower with the side-chain modified 3β-hydroxy-24S-methyl-5α-cholesta-8(14),22-dien-15-one than with the previously described 3β-hydroxy-5α-cholest-8(14)-en-15-one. A surprising finding was that this novel side-chain modified sterol was metabolized mainly in the C-28 position by CYP27A1. The data on 28-hydroxylation by human CYP27A1 provide new insights on the catalytic properties and substrate specificity of this enzyme. The finding that 3β-hydroxy-24S-methyl-5α-cholesta-8(14),22-dien-15-one with a modified side chain is metabolized at a dramatically slower rate than the previously described 15-ketosterol with unmodified side chain may be important for future development of synthetic cholesterol lowering sterols. PMID:18603016

  2. Metabolism of a novel side chain modified Delta8(14)-15-ketosterol, a potential cholesterol lowering drug: 28-hydroxylation by CYP27A1.

    Science.gov (United States)

    Pettersson, Hanna; Norlin, Maria; Andersson, Ulla; Pikuleva, Irina; Björkhem, Ingemar; Misharin, Alexander Yu; Wikvall, Kjell

    2008-08-01

    The synthetic inhibitors of sterol biosynthesis, 3beta-hydroxy-5alpha-cholest-8(14)-en-15-one and 3beta-hydroxy-24S-methyl-5alpha-cholesta-8(14),22-dien-15-one, are of interest as potential cholesterol lowering drugs. Rapid metabolism of synthetic 15-ketosterols may lead to a decrease, or loss, of their potency to affect lipid metabolism. 3beta-Hydroxy-5alpha-cholest-8(14)-en-15-one is reported to be rapidly side chain oxygenated by rat liver mitochondria. In an attempt to reduce this metabolism, the novel side chain modified 15-ketosterol 3beta-Hydroxy-24S-methyl-5alpha-cholesta-8(14),22-dien-15-one was synthesized. We have examined the metabolism by recombinant human CYP27A1 of this novel side chain modified 3beta-hydroxy-24S-methyl-5alpha-cholesta-8(14),22-dien-15-one and compared the rate of metabolism with that of the previously described 3beta-hydroxy-5alpha-cholest-8(14)-en-15-one. Both sterols were found to be efficiently metabolized by recombinant human CYP27A1. None of the two 15-ketosterols was significantly metabolized by microsomal 7alpha-hydroxylation. Interestingly, CYP27A1-mediated product formation was much lower with the side chain modified 3beta-hydroxy-24S-methyl-5alpha-cholesta-8(14),22-dien-15-one than with the previously described 3beta-hydroxy-5alpha-cholest-8(14)-en-15-one. A surprising finding was that this novel side chain modified sterol was metabolized mainly in the C-28 position by CYP27A1. The data on 28-hydroxylation by human CYP27A1 provide new insights on the catalytic properties and substrate specificity of this enzyme. The finding that 3beta-hydroxy-24S-methyl-5alpha-cholesta-8(14),22-dien-15-one with a modified side chain is metabolized at a dramatically slower rate than the previously described 15-ketosterol with unmodified side chain may be important for future development of synthetic cholesterol lowering sterols.

  3. Analytical application of polymethylene blue-multiwalled carbon nanotubes modified glassy carbon electrode on anticancer drug irinotecan and determination of its ionization constant value.

    Science.gov (United States)

    Karadas, Nurgul; Sanli, Senem; Akmese, Bediha; Dogan-Topal, Burcu; Can, Alp; Ozkan, Sibel A

    2013-10-15

    The voltammetric behavior of anticancer drug irinotecan (IRT) was investigated at poly (methylene blue)/multi-walled carbon nanotube (PMB/MWCNT) modified glassy carbon electrode (GCE). The modified electrode surface was characterized by a scanning electron microscope (SEM). The PMB/MWCNT modified GCE exhibits a distinct shift of the oxidation potential of IRT on the cathodic direction and a considerable enhancement of the peak current compared with bare electrode. The calibration curve was linear between the concentration range 8.0 × 10(-6) and 8.0 × 10(-5)M with the detection limit of 2.14 × 10(-7)M by differential pulse voltammetry in pH 10.0 Britton-Robinson buffer solution. Controlled potential coulometry was applied to find transferred electron numbers due to the oxidation of IRT. In this study, the pKa value of IRT was also determined by the dependence of the retention factor on the pH of the mobile phase. The effect of the mobile phase composition on the ionization constant was studied by measuring the pKa at different acetonitrile-water mixtures, ranging between 35 and 50% (v/v) using the reversed-phase liquid chromatography (RP-LC) method with UV detector. IRT was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions, and the stressed samples were detected by the proposed method. Sensitive, rapid, and fully validated electrochemical and RP-LC methods for the determination of IRT in its dosage form were presented in details. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Linalool loaded on glutathione-modified gold nanoparticles: a drug delivery system for a successful antimicrobial therapy.

    Science.gov (United States)

    Jabir, Majid S; Taha, Ali A; Sahib, Usama I

    2018-04-04

    In the present study, antimicrobial activity of Linalool loaded on Glutathione-modified Gold nanoparticles prepared by novel method was investigated. The aim of this study is to evaluate the antimicrobial activity of Linalool-gold nanoparticles (LIN-GNPs) against Gram's positive bacteria Staphylococcus aureus, Gram's negative bacteria Escherichia coli, and against Leishmania tropica. Gold nanoparticles were synthesized using the chemical method. Colour change, UV-Vis spectrum, FTIR and SEM confirmed the characterization of gold nanoparticles and LIN-GNPs. The antibacterial study was including agar well diffusion method, MIC, MBC. The mode of action was determined by cellular material release assay, SEM and AO/EtBr for ROS detection. Anti-parasitic activity was evaluated using MTT assay. FTIR spectral analysis investigated that Linalool was loaded on gold nanoparticles. SEM showed that the Gold nanoparticles and LIN-GNPs were generally found to be spherical in shape and the size was ranged 5-11 nm for GNPs and 15-20 nm for LIN-GNPs. The results of antibacterial activity demonstrated that Linalool alone had low activity against gram-positive and gram-negative bacteria. While the results showed that gram-positive bacteria were more effective by LIN-GNPs. LIN-GNPs acted on the bacterial cell membrane, resulting in loss of integrity and increased permeability of cell wall and stimulated ROS production that leads to damage of bacterial nucleic acid. The anti-parasitic activity results indicated the high activity of LIN-GNPs on L. tropica compared with Linalool and Gold nanoparticles. These results proved that LIN-GNPs have great potential as antimicrobial activity and could be used as a developing strategy for a successful antimicrobial therapeutic agent.

  5. A new pH/organic modifier gradient RP HPLC method for convenient determination of lipophilicity and acidity of drugs as applied to established imidazoline agents.

    Science.gov (United States)

    Wiczling, Paweł; Nasal, Antoni; Kubik, Łukasz; Kaliszan, Roman

    2012-08-30

    Convenient drug candidates testing methods for lipophilicity and acidity are highly requested in modern pharmaceutical research and development strategy. Reversed-phase high-performance liquid chromatography (RP HPLC) might be particularly useful for the determination of both pK(a) and the apparent (pH-dependent) octanol-water partition coefficient, applicable in high-throughput analysis of multi-component mixtures. In this report the pH/organic modifier gradient RP HPLC is presented as a means of simultaneous determination of acidity and lipophilicity of a series of 26 imidazoline-like drugs. The previously theoretically elaborated approach has been applied consisting in retention measurements in a series of methanol gradient runs differing in pH range and duration of the gradient. The simultaneously determined lipophilicity and dissociation constants have been demonstrated to correlate to the respective parameters form calculation chemistry. The proposed approach can be applied to compound mixtures, it requires only minute amounts of substances, and pK(a) values can be determined in the range 3-10 units and lipophilicity log P parameter in the range 0-7 units. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Spectroscopic Study of the Interaction of Carboxyl-Modified Gold Nanoparticles with Liposomes of Different Chain Lengths and Controlled Drug Release by Layer-by-Layer Technology.

    Science.gov (United States)

    Kanwa, Nishu; De, Soumya Kanti; Adhikari, Chandan; Chakraborty, Anjan

    2017-12-21

    In this article, we investigate the interactions of carboxyl-modified gold nanoparticles (AuC) with zwitterionic phospholipid liposomes of different chain lengths using a well-known membrane probe PRODAN by steady-state and time-resolved spectroscopy. We use three zwitterionic lipids, namely, dipalmitoylphosphatidylcholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), which are widely different in their phase transition temperatures to form liposome-AuC assemblies. The steady-state and time-resolved studies indicate that the AuC brings in stability toward liposomes by local gelation. We observe that the bound AuC detach from the surface of the liposomes under pH ≈ 5 due to protonation of the carboxyl group, thus eliminating the electrostatic interaction between nanoparticles and head groups of liposomes. The detachment rate of AuC from the liposome-AuC assemblies is different for the aforementioned liposomes due to differences in their fluidity. We exploited the phenomena for the controlled release of a prominent anticancer drug Doxorubicin (DOX) under acidic conditions for different zwitterionic liposomes. The drug release rate was further optimized by coating of liposome-AuC assemblies with oppositely charged polymer (P), polydiallyldimethylammonium chloride, followed by a mixture of lipids L (DMPC:DMPG) and again with a polymer in a layer-by-layer fashion to obtain capsule-like structures. This system is highly stable for weeks, as confirmed by field-emission scanning electron microscopy (FE-SEM) and confocal laser scanning microscopy (CLSM) imaging, and inhibits premature release. The layer coating was confirmed by hydrodynamic size and zeta potential measurements of the systems. The capsules obtained are of immense importance as they can control release of the drug from the systems to a large extent.

  7. Metabolically active extracellular vesicles released from hepatocytes under drug-induced liver-damaging conditions modify serum metabolome and might affect different pathophysiological processes.

    Science.gov (United States)

    Royo, Felix; Palomo, Laura; Mleczko, Justyna; Gonzalez, Esperanza; Alonso, Cristina; Martínez, Ibon; Pérez-Cormenzana, Miriam; Castro, Azucena; Falcon-Perez, Juan M

    2017-02-15

    Hepatocytes are involved in the endogenous and drug metabolism; many of the enzymes involved in those processes are incorporated into extracellular vesicles and secreted into the bloodstream. Liver-damaging conditions modify the molecular cargo of those vesicles significantly. However, no information about the effect of these hepatic vesicles on the extracellular environment is available. Drug-induced liver damage increases the number of circulating extracellular vesicles and affects the release and content of hepatocyte-derived vesicles. In this work, we evaluated the metabolic effect of these vesicles on the composition of the serum. We performed a targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) metabolomics analysis of serum samples. The samples had been first incubated with hepatic extracellular vesicles from hepatocytes challenged with acetaminophen or diclofenac. The incubation affected the serum levels of 67 metabolites, such as amino acids and different species of lipids. The metabolites included various species of phosphatidylcholines and phosphatidylethanolamines. These compounds are the components of biological membranes; our observations suggest that the vesicles might take part in remodelling and maintenance of the membranes. Alterations in the levels of some other serum metabolites might have deleterious consequences, for example, the tetracosanoic acid with its cardiovascular effects. However, some of the metabolites whose levels were increased, including alpha-linoleic and tauroursodeoxycholic acids, have been reported to have a protective effect. Our targeted metabolomics analysis indicated that the hepatic extracellular vesicles act as nano-metabolic machines supplying the extracellular environment with the means to integrate diverse tissue responses. In conclusion, we show that the hepatic extracellular vesicles are metabolically active and might play a role in the physiopathological response to hepatic insults

  8. Antibacterial and antibiotic-resistance modifying activity of the extracts and compounds from Nauclea pobeguinii against Gram-negative multi-drug resistant phenotypes.

    Science.gov (United States)

    Seukep, Jackson A; Sandjo, Louis P; Ngadjui, Bonaventure T; Kuete, Victor

    2016-07-07

    Multi-drug resistance of Gram-negative bacteria constitutes a major obstacle in the antibacterial fight worldwide. The discovery of new and effective antimicrobials and/or resistance modulators is necessary to combat the spread of resistance or to reverse the multi-drug resistance. In this study, we investigated the antibacterial and antibiotic-resistance modifying activities against 29 Gram-negative bacteria including multi-drug resistant (MDR) phenotypes of the methanol extracts from Nauclea pobeguiinii leaves (NPL), Nauclea pobeguiinii bark (NPB) and six compounds from the bark extract, identified as 3-acetoxy-11-oxo-urs-12-ene (1), p-coumaric acid (2), citric acid trimethyl ester (3), resveratrol (4), resveratrol β- D -glucopyranoside (5) and strictosamide (6). The broth microdilution method was used to determine the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of crude extracts and compounds as well as the antibiotic-resistance modifying effects of MPB and 4. MIC determinations indicate values ranging from 32-1024 μg/mL for NPB and NPL on 89.7 % and 69.0 % of the tested bacterial strains respectively. MIC values below 100 μg/mL were obtained with NPB against Escherichia coli ATCC10536, AG100 and Enterobacter aerogenes CM64 strains. The lowest MIC value for crude extracts of 32 μg/mL was obtained with NPB against E. coli ATCC10536. Compound 4 was active all tested bacteria, whilst 1, 3 and 6 displayed weak and selective inhibitory effects. The corresponding MIC value (16 μg/mL) was obtained with 4 against Klebsiella pneumoniae KP55 strain. Synergistic effects of the combination of NPB with chloramphenicol (CHL), kanamycin (KAN) as well as that of compound 4 with streptomycin (STR) and ciprofloxacin (CIP) were observed. The present study provides information on the possible use of Nauclea pobeguinii and compound 4 in the control of Gram-negative bacterial infections including MDR phenotypes. It also indicates

  9. Development of a simple one-pot extraction method for various drugs and metabolites of forensic interest in blood by modifying the QuEChERS method.

    Science.gov (United States)

    Matsuta, Shuntaro; Nakanishi, Keiko; Miki, Akihiro; Zaitsu, Kei; Shima, Noriaki; Kamata, Tooru; Nishioka, Hiroshi; Katagi, Munehiro; Tatsuno, Michiaki; Tsuboi, Kento; Tsuchihashi, Hitoshi; Suzuki, Koichi

    2013-10-10

    A rapid and convenient extraction method has been developed for the determination of various drugs and metabolites of forensic interest in blood by modifying the dispersive solid-phase extraction method "QuEChERS". The following 13 analytes with various chemical properties were used for the method development and its validation: amphetamine, methamphetamine, zolpidem, the carboxylate-form major metabolite of zolpidem M-1, flunitrazepam, 7-aminoflunitrazepam, phenobarbital, triazolam, α-hydroxytriazolam, brotizolam, α-hydroxybrotizolam, chlorpromazine, and promethazine. The modification of the QuEChERS method includes the use of relatively large amounts of inorganic salts in order to coagulate blood, which allows easy isolation of the organic extract phase. A combination of 100 mg anhydrous magnesium sulfate as a dehydrating agent, 50mg sodium chloride as a salting-out agent, and 500 μL acetonitrile containing 0.2% acetic acid as the organic solvent provided the optimum conditions for processing a 100 μL whole blood sample. The recoveries of the analytes spiked into whole blood at 0.5 μg/mL ranged between 59% and 93%. Although the addition of the graphitized carbon Envi-carb for cleanup decreased the recoveries of zolpidem and its carboxylate-form metabolite M-1, it was very effective in avoiding interferences by cholesterol. The present method can provide a rapid, effective, user-friendly, and relatively hygienic method for the simultaneous extraction of a wide range of drugs and metabolites in whole blood specimens. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. A retrospective study of patients with adult-onset Still's disease: is pericarditis a possible predictor for biological disease-modifying anti-rheumatic drugs need?

    Science.gov (United States)

    Dall'Ara, Francesca; Frassi, Micol; Tincani, Angela; Airò, Paolo

    2016-08-01

    The aims of this study were to look for clinical or serological markers able to predict the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in patients with adult-onset Still's disease (AOSD) and to evaluate the efficacy and safety of bDMARDs in AOSD. In a single-center retrospective study, 39 patients with AOSD were divided into two groups according to whether they were ever treated with bDMARDs or not. Literature was searched for articles dealing with possible predictors of the use of bDMARDs in AOSD. Among the 18 AOSD patients who received at least one bDMARD, the prevalence of pericarditis was higher than that in the other patients [p = 0.014, odds ratio (OR) = 13.4, 95 % confidence interval (CI) = 1.45 to 122]. Literature search retrieved another paper dealing with predictors of bDMARDs need in AOSD: the analysis pooling data from our series and this previous report confirmed pericarditis at disease onset as a predictor of bDMARDs need (p = 0.028, OR = 3.62, 95 % CI = 1.22 to 10.7). A complete remission was observed in 17 out of 18 patients treated with bDMARDs, allowing withdrawal or tapering of corticosteroid therapy (p Pericarditis at disease onset may be a predictor of bDMARDs need in AOSD. These drugs have a good efficacy and safety profile and should be considered for patients not responding to conventional therapy.

  11. Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study

    DEFF Research Database (Denmark)

    Hetland, M.L.; Stengaard-Pedersen, K.; Junker, P.

    2008-01-01

    OBJECTIVE: To investigate whether clinical and radiographic disease control can be achieved and maintained in patients with early, active rheumatoid arthritis (RA) during the second year of aggressive treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and intra-articular c...

  12. Determinants of adherence to disease modifying anti-rheumatic drugs in White British and South Asian patients with rheumatoid arthritis: a cross sectional study.

    Science.gov (United States)

    Kumar, Kanta; Raza, Karim; Nightingale, Peter; Horne, Robert; Chapman, Sarah; Greenfield, Sheila; Gill, Paramjit

    2015-12-29

    Rheumatoid arthritis (RA) is a common chronic inflammatory disease causing joint damage, disability, and reduced life expectancy. Highly effective drugs are now available for the treatment of RA. However, poor adherence to drug regimens remains a significant barrier to improving clinical outcomes in RA. Poor adherence has been shown to be linked to patients' beliefs about medicines with a potential impact on adherence. These beliefs are reported to be different between ethnic groups. The purpose of this study was to identify potential determinants of adherence to disease modifying anti-rheumatic drugs (DMARDs) including an assessment of the influence of beliefs about medicines and satisfaction with information provided about DMARDs and compare determinants of adherence between RA patients of White British and South Asian. RA patients of either White British (n = 91) or South Asian (n = 89) origin were recruited from secondary care. Data were collected via questionnaires on patients': (1) self-reported adherence (Medication Adherence Report Scale-MARS); (2) beliefs about medicines (Beliefs about Medicines Questionnaire-BMQ); (3) illness perceptions (Illness Perceptions Questionnaire-IPQ) and (4) satisfaction with information about DMARDs (Satisfaction with Information about Medicines questionnaire-SIMS). In addition, clinical and demographic data were collected. The results revealed that socio-demographic factors only explained a small amount of variance in adherence whereas illness representations and treatment beliefs were more substantial in explaining non-adherence to DMARDs. Patients' self-reported adherence was higher in White British than South Asian patients (median 28 (interquartile range 26-30) vs median 26 (interquartile range 23-30) respectively; P = 0.013, Mann-Whitney test). Patients who reported lower adherence were more dissatisfied with the information they had received about their DMARDs (P problems subscale) and had more negative beliefs about

  13. Safety of Biologic and Nonbiologic Disease-modifying Antirheumatic Drug Therapy in Veterans with Rheumatoid Arthritis and Hepatitis C Virus Infection.

    Science.gov (United States)

    Burton, Mary Jane; Curtis, Jeffrey R; Yang, Shuo; Chen, Lang; Singh, Jasvinder A; Mikuls, Ted R; Winthrop, Kevin L; Baddley, John W

    2017-05-01

    To examine the effect of disease-modifying antirheumatic drug (DMARD) therapy on hepatotoxicity among patients with rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection. We identified biologic and nonbiologic treatment episodes of patients with RA using the 1997-2011 national data from the US Veterans Health Administration. Eligible episodes had HCV infection (defined by detectable HCV RNA) and subsequently initiated a new biologic or nonbiologic DMARD. Cohort entry required a baseline alanine aminotransferase (ALT) biologic/DMARD therapy. The primary outcome of interest was hepatotoxicity, defined as ALT elevation ≥ 100 IU/l or increase in HCV RNA of 1 log or more, and was examined within the first year of biologic/DMARD use. Results were reported as the cumulative incidence of treatment episodes achieving predefined hepatotoxicity at 3, 6, and 12 months after biologic/DMARD initiation. RA patients with HCV (n = 748) were identified and contributed 1097 biologic/DMARD treatment episodes. Overall, ALT elevations were uncommon, with 37 (3.4%) hepatotoxicity events occurring within 12 months. Treatment episodes with biologic DMARD demonstrated more frequency of hepatotoxicity than did nonbiologic DMARD (4.8% vs 2.3%, p = 0.03). Among treatment episodes involving hepatotoxicity events, the majority occurred within 6 months of DMARD initiation (29/37, 78%). In US veterans with HCV and RA receiving biologic and nonbiologic DMARD, the frequency of hepatotoxicity (ALT ≥ 100 IU/l) was low, with a higher frequency observed in treatment episodes with current biologic use.

  14. Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

    Directory of Open Access Journals (Sweden)

    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs versus DMARDs alone for ankylosing spondylitis (AS with reduced pulmonary function vital capacity (FVC%. Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT, Borg scale after 6MWT, and St. George’s Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P=0.04. Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5% in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55% in the DMARDs group (P=0.04. Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%.

  15. Eudragit ® FS 30 D polymeric films containing chondroitin sulfate as candidates for use in coating seeking modified delivery of drugs

    Directory of Open Access Journals (Sweden)

    Camila Borges dos Reis

    Full Text Available ABSTRACT Polymeric films associating different concentrations of Eudragit(r FS 30 D (EFS and chondroitin sulfate (CS were produced by casting for the development of a new target-specific site material. Formed films kept a final polymer mass of 4% (w/v in the following proportions: EFS 100:00 CS (control, EFS 95:05 CS, EFS 90:10 CS and EFS 80:20 CS. They were analyzed for physical and chemical characteristics using Fourier transform infrared spectroscopy (FTIR, scanning electron microscopy (SEM and Raman spectroscopy. Furthermore, they were characterized by their water vapor permeability and degree of hydration at different conditions simulating the gastrointestinal tract. No chemical interactions were observed between CS and EFS, suggesting only a physical interaction between them in the different combinations tested. The results suggest that EFS and CS, when combined, may form films that are candidates for coating processes seeking a modified drug delivery, especially due to the synergism between pH dependency and specific biodegradability properties by the colonic microbiota. EFS 90:10 CS proved to be the most suitable for this purpose considering hydration and permeability characteristics of different associations analyzed.

  16. Different Effects of the Immunomodulatory Drug GMDP Immobilized onto Aminopropyl Modified and Unmodified Mesoporous Silica Nanoparticles upon Peritoneal Macrophages of Women with Endometriosis

    Directory of Open Access Journals (Sweden)

    Yuliya Antsiferova

    2013-01-01

    Full Text Available The aim of the present work was to compare in vitro the possibility of application of unmodified silica nanoparticles (UMNPs and modified by aminopropyl groups silica nanoparticles (AMNPs for topical delivery of immunomodulatory drug GMDP to the peritoneal macrophages of women with endometriosis. The absence of cytotoxic effect and high cellular uptake was demonstrated for both types of silica nanoparticles. The immobilization of GMDP on the UMNPs led to the suppression of the stimulatory effect of GMDP on the membrane expression of scavenger receptors SR-AI and SR-B, mRNAs expression of NOD2 and RAGE, and synthesis of proteolytic enzyme MMP-9 and its inhibitor TIMP-1. GMDP, immobilized onto AMNPs, enhanced the initially reduced membrane expression of SRs and increased NOD2, RAGE, and MMP-9 mRNAs expression by macrophages. Simultaneously high level of mRNAs expression of factors, preventing undesirable hyperactivation of peritoneal macrophages (SOCS1 and TIMP-1, was observed in macrophages incubated in the presence of GMDP, immobilized onto AMNPs. The effect of AMNPs immobilized GMDP in some cases exceeded the effect of free GMDP. Thus, among the studied types of silica nanoparticles, AMNPs are the most suitable nanoparticles for topical delivery of GMDP to the peritoneal macrophages.

  17. Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer.

    Science.gov (United States)

    Zhu, Dunwan; Tao, Wei; Zhang, Hongling; Liu, Gan; Wang, Teng; Zhang, Linhua; Zeng, Xiaowei; Mei, Lin

    2016-01-01

    Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle (NP) surfaces with ligands and/or additional polymeric layers. In this work, we developed DTX-loaded formulations using polydopamine-modified NPs synthesized using D-α-tocopherol polyethylene glycol 1000 succinate-poly(lactide) (pD-TPGS-PLA/NPs). To target liver cancer cells, galactosamine was conjugated on the prepared NPs (Gal-pD-TPGS-PLA/NPs) to enhance the delivery of DTX via ligand-mediated endocytosis. The size and morphology of pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs changed obviously compared with TPGS-PLA/NPs. In vitro studies showed that TPGS-PLA/NPs, pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs had similar release profiles of DTX. Both confocal laser scanning microscopy and flow cytometric results showed that coumarin 6-loaded Gal-pD-TPGS-PLA/NPs had the highest cellular uptake efficiency in liver cancer cell line HepG2. Moreover, DTX-loaded Gal-pD-TPGS-PLA/NPs inhibited the growth of HepG2 cells more potently than TPGS-PLA/NPs, pD-TPGS-PLA/NPs, and a clinically available DTX formulation (Taxotere®). The in vivo biodistribution experiments show that the Gal-pD-TPGS-PLA/NPs are specifically targeted to the tumor. Furthermore, the in vivo anti-tumor effects study showed that injecting DTX-loaded Gal-pD-TPGS-PLA/NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. These results suggest that Gal-pD-TPGS-PLA/NPs prepared in the study specifically interacted with the hepatocellular carcinoma cells through ligand-receptor recognition and they may be used as a potentially eligible drug delivery system targeting liver cancers. Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle surfaces with ligands and/or additional polymeric layers. In this work, we developed docetaxel (DTX)-loaded formulations using polydopamine-modified NPs synthesized from D-α-tocopherol polyethylene glycol 1000 succinate

  18. CONCEPT OF DRUG INTERACTION

    OpenAIRE

    Singh Nidhi

    2012-01-01

    Drug interaction is an increasingly important cause of adverse reactions (ADR), and is the modification of the effect of one drug (object) by the prior or concomitant administration of another drug (precipitant drug). Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin) are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or act...

  19. Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs.

    Science.gov (United States)

    Takakubo, Yuya; Oki, Hiroharu; Naganuma, Yasushi; Saski, Kan; Sasaki, Akiko; Tamaki, Yasunobu; Suran, Yang; Konta, Tsuneo; Takagi, Michiaki

    2017-01-01

    Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular distribution of PDPN and it's relationships with inflammation was studied in RA treated with biologic disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD). PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of inflammation and cell-typing. Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA. PDPN was markedly increased in the immunologically inflamed RA synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new marker of residual arthritis in local joints for inflammation-associated severe RA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Disease-modifying anti-rheumatic drug usage, prescribing patterns and disease activity in rheumatoid arthritis patients in community-based practice.

    Science.gov (United States)

    Montag, K; Gingold, M; Boers, A; Littlejohn, G

    2011-06-01

    Our aim was to examine the spectrum of disease activity and usage of disease-modifying anti-rheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients seen over a period of 12 months in community-based rheumatology practice. Data were prospectively collected on 1059 consecutive RA patients who attended two private, community-based rheumatology clinics from 1 May 2007 to 1 May 2008. Information on patient demographics, medication history and disease activity was collected. Life table graphs were developed to track medication retention over time. Statistical significance was determined by log-rank tests. One thousand and fifty-nine patients with RA were entered into the database over a 12-month period. Eight hundred and twenty-six patients (85%) were treated with single or combination conventional DMARD compared with 159 patients (15%) on a biologic DMARD either alone or in combination. Methotrexate monotherapy was the most commonly prescribed DMARD, used in 41% of patients studied. Almost half (47%) were on combination DMARD therapy. Methotrexate and tumour necrosis factor inhibitors had the highest retention rate over 12 and 30 months since first prescription. A large proportion of patients (47%) had moderate disease activity. Rates of biologic DMARD usage were similar to other studies and the predominance of methotrexate use was also in keeping with current recommendations for management of RA. There appears to be a significant unmet need for improved disease control among RA patients with moderate disease activity, which requires further investigation. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  1. Efficacy of yttrium-90 synovectomy across a spectrum of arthropathies in an era of improved disease modifying drugs and treatment protocols.

    Science.gov (United States)

    Wong, Yiisong; Cherk, Martin H; Powell, Anne; Cicuttini, Flavia; Bailey, Michael; Kalff, Victor

    2014-01-01

    To evaluate clinical response rates, duration of response and complication rates of yttrium radiosynovectomy (RSV) in an era of improved disease modifying antirheumatic drugs (DMARDS) and increased access to replacement therapy for clotting factor deficiencies introduced in the mid 2000s. A retrospective review of 167 consecutive joints treated with RSV between 2000 and 2010 was conducted. Clinical response and complication rates in 167 joints (119 patients: 45 female,74 male, mean age 52 years) with rheumatoid, psoriatic, hemophilic, large joint mono-arthropathy and miscellaneous arthropathies refractory to conventional therapy were reviewed. Clinical response was determined at 3 months with responding patients reviewed again at 36 months to assess whether response was sustained. Comparison of response rates pre- and post-introduction of improved DMARDS in the mid 2000s was also performed. Satisfactory clinical response was highest for large joint mono-arthropathy (85%) and lower for other arthropathies (47-64%). A strong relationship was demonstrated between degree and duration of response with 90% of complete responders compared to 41% of incomplete responders having a sustained response at 36 months (P ≤ 0.0001). Major complication rates were low (1%). No difference was demonstrated in response rates pre- and post-introduction of improved DMARDS in the mid 2000s. In an era of improved DMARDS, yttrium synovectomy remains a safe and effective procedure across a broad spectrum of arthropathies and should continue to be considered in cases refractory to conventional therapies. Complete responders can be expected to have symptom relief for at least 36 months and complication rates are low. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  2. Delayed wound healing and postoperative surgical site infections in patients with rheumatoid arthritis treated with or without biological disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Tada, Masahiro; Inui, Kentaro; Sugioka, Yuko; Mamoto, Kenji; Okano, Tadashi; Kinoshita, Takuya; Hidaka, Noriaki; Koike, Tatsuya

    2016-06-01

    Biological disease-modifying antirheumatic drugs (bDMARDs) have become more popular for treating rheumatoid arthritis (RA). Whether or not bDMARDs increase the postoperative risk of surgical site infection (SSI) has remained controversial. We aimed to clarify the effects of bDMARDs on the outcomes of elective orthopedic surgery. We used multivariate logistic regression analysis to analyze risk factors for SSI and delayed wound healing among 227 patients with RA (mean age, 65.0 years; disease duration, 16.9 years) after 332 elective orthopedic surgeries. We also attempted to evaluate the effects of individual medications on infection. Rates of bDMARD and conventional synthetic DMARD (csDMARD) administration were 30.4 and 91.0 %, respectively. Risk factors for SSI were advanced age (odds ratio [OR], 1.11; P = 0.045), prolonged surgery (OR, 1.02; P = 0.03), and preoperative white blood cell count >10,000/μL (OR, 3.66; P = 0.003). Those for delayed wound healing were advanced age (OR, 1.16; P = 0.001), prolonged surgery (OR, 1.02; P = 0.007), preoperative white blood cell count >10,000/μL (OR, 4.56; P = 0.02), and foot surgery (OR, 6.60; P = 0.001). Risk factors for SSI and medications did not significantly differ. No DMARDs were risk factors for any outcome examined. Biological DMARDs were not risk factors for postoperative SSI. Foot surgery was a risk factor for delayed wound healing.

  3. Simultaneous Response in Several Domains in Patients with Psoriatic Disease Treated with Etanercept as Monotherapy or in Combination with Conventional Synthetic Disease-modifying Antirheumatic Drugs.

    Science.gov (United States)

    Behrens, Frank; Meier, Lothar; Prinz, Jörg C; Jobst, Jürgen; Lippe, Ralph; Löschmann, Peter-Andreas; Lorenz, Hanns-Martin

    2018-04-01

    To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously. A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary. Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group. While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.

  4. Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drugs in rheumatoid arthritis: results of the GO-MORE study in Spain.

    Science.gov (United States)

    Alonso, Alberto; González, Carlos M; Ballina, Javier; García Vivar, María L; Gómez-Reino, Juan J; Marenco, Jose Luis; Fernández-Nebro, Antonio; Ordás, Carmen; Cea-Calvo, Luis; Arteaga, María J; Sanmartí, Raimon

    2015-01-01

    To assess the efficacy and safety of golimumab in the 140 patients included in Spain as the first part of the GO-MORE trial, a multinational study involving patients with active rheumatoid arthritis (RA) despite treatment with different disease-modifying antirheumatic drugs (DMARDs). The patients received subcutaneous golimumab 50mg once a month during 6 months. The primary endpoint was the percentage of individuals with a good or moderate EULAR DAS28-ESR response after 6 months of treatment. A total of 140 patients were included. Of these, 76.4% had very active disease (DAS28-ESR>5.1). 76.4% were taking methotrexate, 40.0% other DMARDs in monotherapy or combined, and 65.0% received corticosteroids. After 6 months, 82.9% of the patients showed a good or moderate EULAR response, 41.4% had low disease activity, and 30.7% were in remission. The percentage of responders one month after the first dose was 69.3%. The efficacy was similar in patients treated with methotrexate or other DMARDs, with different methotrexate doses, with or without corticosteroids, or in subjects who had failed one or more DMARDs. The response to golimumab was observed from the first dose. Golimumab was well tolerated and its safety profile was consistent with the findings of previous studies. Serious adverse events were reported in 11 patients (7.9%). The addition of subcutaneous golimumab 50 mg once a month to different DMARDs in patients with active RA yielded a moderate or good response after 6 months in 82.9% of the cases. The response was observed early, from the start of the second month, after a single dose of golimumab. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  5. Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Tetsuo Kobayashi

    Full Text Available To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD in patients with rheumatoid arthritis (RA.In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs related to RA were also determined.After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP (P = 0.04 for both and anti-cyclic citrullinated peptide (CCP IgG levels (P = 0.03 and P = 0.04 than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both and the anti-CCP IgG levels (P = 0.02 for both from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006, after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs.The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA.

  6. Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor.

    Science.gov (United States)

    Abdulkader, Omer Ahmad Fatheddin; Qushmaq, Khalid; Aljishi, Faiza

    2016-01-01

    Tocilizumab (TCZ) is a humanized anti-human IL-6R antibody, a novel therapy for rheumatoid arthritis (RA) patients who fail treatment with disease modifying anti-rheumatic drugs (DMARDs) or anti-tumor necrosis factor (anti-TNFs). To assess the safety and efficacy of TCZ monotherapy or in combination with non-biologic DMARDs or anti-TNFs in moderate to severe active RA. Prospective, phase III, multi-center, open-label, single arm, 24-week trial. Three centers in Saudi Arabia. The study included consecutive RA patients infused with TCZ (8 mg/kg) over 60 minutes every 4 weeks (up to 6 times), either alone or with non-biologic DMARDs. Patients were followed for 24 weeks. Patients with good/moderate European League Against Rheumatism responses, continued on TCZ as long as commerically available or for 1 year. Disease activity measured by DAS28 score. Of 28 patients enrolled from 2 November 2011 to 12 May 2013 (18 months), 21 completed (77.8%) and 7 (25%) discontinued TCZ therapy. One patient was excluded from the intent-to-treat analysis. Efficacy analysis showed a significant difference (P modification or death. TCZ monotherapy or in combination with non-biologic DMARDs resulted in a significant effect on the endpoints in moderate to severe RA in Saudi Arabia, which is consistent with other published reports. No information on tapering of steroid therapy, lack of follow-up data of all 28 patients, lack of data on long-term effects of TCZ on lipid levels and the need for statins. (ClinicalTrials.gov identifier: NCT01326962).

  7. The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic–Lipophilic Matrices

    OpenAIRE

    Dvořáčková, Kateřina; Doležel, Petr; Mašková, Eliška; Muselík, Jan; Kejdušová, Martina; Vetchý, David

    2013-01-01

    The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic–lipophilic (hypromellose–montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumar...

  8. Biologic Disease-Modifying Antirheumatic Drugs and Risk of High-Grade Cervical Dysplasia and Cervical Cancer in Rheumatoid Arthritis: A Cohort Study.

    Science.gov (United States)

    Kim, Seoyoung C; Schneeweiss, Sebastian; Liu, Jun; Karlson, Elizabeth W; Katz, Jeffrey N; Feldman, Sarah; Solomon, Daniel H

    2016-09-01

    Recent research showed an increased risk of high-grade cervical dysplasia and cervical cancer associated with rheumatoid arthritis (RA). The purpose of this study was to examine whether this risk was associated with the use of biologic versus nonbiologic disease-modifying antirheumatic drugs (DMARDs). We identified RA patients in the US Medicaid and commercial insurance databases (for the years 2000-2012) who were starting treatment with either a biologic or a nonbiologic DMARD. High-grade cervical dysplasia or cervical cancer was identified with a validated claims-based algorithm, and we assessed utilization of gynecologic procedures. To control for potential confounders, those starting therapy with a biologic DMARD were matched 1:1 to those starting therapy with a nonbiologic DMARD according to the propensity score (PS). Hazard ratios (HRs) and rate ratios (RRs) in the PS-matched Medicaid and commercial insurance cohorts were pooled by an inverse variance-weighted fixed-effects model. We included 14,729 pairs of patients initiating biologic and nonbiologic DMARDs from the Medicaid cohort and 7,538 pairs from the commercial insurance cohort. During 73,389 person-years of active treatment with either biologic or nonbiologic DMARDs, 95 cases of high-grade cervical dysplasia or cervical cancer occurred in the 2 cohorts. The HR for high-grade cervical dysplasia or cervical cancer associated with biologic DMARD use was 1.25 (95% confidence interval [95% CI] 0.78-2.01) in the Medicaid cohort and 1.63 (95% CI 0.62-4.27) in the commercial insurance cohort, with a pooled HR of 1.32 (95% CI 0.86-2.01). The rate of gynecologic procedures involving the uterine cervix was not different between the 2 groups (pooled RR 0.96 [95% CI 0.90-1.02]). Among women with RA, initiation of therapy with a biologic DMARD was associated with a numerically significant, but not statistically significant, increase in the risk of high-grade cervical dysplasia or cervical cancer as compared to

  9. Examining Time to Initiation of Biologic Disease-modifying Antirheumatic Drugs and Medication Adherence and Persistence Among Texas Medicaid Recipients With Rheumatoid Arthritis.

    Science.gov (United States)

    Kim, Gilwan; Barner, Jamie C; Rascati, Karen; Richards, Kristin

    2016-03-01

    Little is known about the transition from nonbiologic disease-modifying antirheumatic drugs (DMARDs) to biologic DMARDs or about individual nonbiologic DMARD use patterns among patients with rheumatoid arthritis (RA). This study examined time to initiation of biologic DMARDs and nonbiologic DMARD medication adherence and persistence among Texas Medicaid recipients with RA taking nonbiologic DMARDs. In this retrospective study (July 1, 2003-December 31, 2010) of the Texas Medicaid database, patients were aged 18 to 62 years at index, were diagnosed with RA (International Classification of Diseases, Ninth Revision, Clinical Modification, code 714.xx), had no claims for nonbiologic or biologic DMARDs in the preindex period, and had a minimum of 2 prescription claims for the same nonbiologic DMARD in the postindex period. Kaplan-Meier survival analysis and log-rank tests were used to compare time to initiation of biologic DMARDs according to nonbiologic DMARD type and therapy. Adherence and persistence were examined according to nonbiologic type and therapy by using ANOVA models and χ(2), Duncan, and t tests. On average, patients were 47.9 (± 10.4) years of age, mostly female (89.1%) and Hispanic (55.2%). Methotrexate (MTX) and leflunomide (LEF) users took the shortest time to initiate biologic DMARDs (207 [190] days and 188 [205] days, respectively). LEF users had the highest mean adherence of 37.5% (27.5%), which was similar to MTX users (35.7% [26.9%]), whereas dual-therapy users had the lowest mean adherence at 17.1% (14.4%). Sulfasalazine users (108 [121] days) had the lowest persistence, whereas LEF (227 [231] days) and MTX (211 [222] days) users had the longest persistence. Nonbiologic DMARD monotherapy users were more adherent than dual-therapy users (32.6% [25.8%] vs 17.1% [14.4%]). These results should be interpreted in light of some study limitations, such as using proportion of days covered as a proxy for adherence, not having clinical data to control for

  10. Polymer brush hexadecyltrimethylammonium bromide (CTAB) modified poly (propylene-g-styrene sulphonic acid) fiber (ZB-1): CTAB/ZB-1 as a promising strategy for improving the dissolution and physical stability of poorly water-soluble drugs.

    Science.gov (United States)

    Cao, Jinxu; Yang, Baixue; Wang, Yumei; Wei, Chen; Wang, Hongyu; Li, Sanming

    2017-11-01

    The feasibility of polymer brush as drug delivery vehicle was demonstrated with the goal of improving the dissolution and physical stability of poorly water-soluble drugs. Polymer brush CTAB/ZB-1 was synthesized by electrostatic interaction using a physical modification method with anionic poly (propylene-g-styrene sulphonic acid) fiber (ZB-1) as the substrate and cationic hexadecyltrimethylammonium bromide (CTAB) as the modifier. The polymer brush structure of CTAB/ZB-1 was validated by atomic force microscopy (AFM) and the channels of brush provided the drug loading sites. Flurbiprofen (FP), a BCS class II representative drug, was selected as the model poorly water-soluble drug to be loaded into this polymer brush. Then the drug loading and release were systematically investigated. Besides, the transformation from crystalline FP to amorphous state was observed by differential scanning calorimeter (DSC). In vitro dissolution in pure water and pH1.2 HCl media with/without 0.1% sodium dodecyl sulfate (SDS) was tested. Moreover, the optimal formulations (namely carrier/drug ratios) were determined. The results demonstrated prominent improvement of dissolution when FP was released from CTAB/ZB-1. After a long time storage, FP remained amorphous in CTAB/ZB-1 according to DSC determinations and performed an approximately equivalent dissolution compared with fresh samples, suggesting the advantage of CTAB/ZB-1 as carrier in enhancing the physical stability of drugs. The study introduced the versatile easily formulated polymer brush CTAB/ZB-1 and demonstrated the potential of polymer brush as an alternative approach for improving the dissolution and physical stability of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Protein kinase C isozymes as regulators of sensitivity to and self-administration of drugs of abuse-studies with genetically modified mice.

    Science.gov (United States)

    Olive, Michael Foster; Newton, Philip M

    2010-09-01

    Studies using targeted gene deletion in mice have revealed distinct roles for individual isozymes of the protein kinase C (PKC) family of enzymes in regulating sensitivity to various drugs of abuse. These changes in drug sensitivity are associated with altered patterns of drug self-administration. The purpose of this review is to summarize behavioral studies conducted on mice carrying targeted deletions of genes encoding specific PKC isozymes (namely the beta, gamma, delta, and epsilon isozymes), and to critically evaluate the possibility of using pharmacological inhibitors of specific PKC isozymes as modulators of the sensitivity to various drugs of abuse, as well as potential aids in the treatment of substance use disorders.

  12. Cell-like features imprinted in the physical nano- and micro-topography of the environment modify the responses to anti-cancer drugs of endometrial cancer cells.

    Science.gov (United States)

    Tan, Li Hui; Sykes, Peter H; Alkaisi, Maan M; Evans, John J

    2017-02-14

    Topographical features of cells at nanometre resolution were fabricated in polystyrene. The study investigated the effect of physical topography on the response of cancer cells to the common anticancer drugs, paclitaxel and doxorubicin. Human endometrial cancer cells (Ishikawa) were incubated on substrates containing cell-like features that had been fabricated using our bioimprint methodology to create moulds of cells with positive (convex) and negative (concave) topography. Control cultures were performed on flat substrates. Effects of the drugs on caspase-3 expression, proliferating nuclear antigen (PCNA) expression, cell number and vascular endothelial growth factor (VEGF) secretion were determined. Results revealed that the topography influenced the cell responses in a drug-dependent manner i.e. paclitaxel effects were sensitive to topography differently to those of doxorubicin. In addition, function signalling pathways were sensitive to the detailed topography i.e. positive imprint and negative imprint induced distinct response patterns. The results in this study show for the first time that a culture surface with cell-like topography, that has both nano- and micro-resolution, influences endometrial cancer cell responses to chemotherapy drugs. The effects are dependent on the topography and also on the chemotherapy drug. In particular, the platforms described have potential to provide substrates with high physical relevancy on which to undertake preclinical testing of new drugs. The method also allows for use of different cell types to provide cell-specific topography. The results imply that physical architecture of the cancer cell environment may be a suitable prospective target to enhance clinical activity of traditional drugs. Additionally or alternatively we provide compelling support for the notion that understanding the physical component of the nano- and micro-environment may encourage a redirection of drug development. Further, our observation that the

  13. Determinants of adherence to disease modifying anti-rheumatic drugs in White British and South Asian patients with rheumatoid arthritis: a cross sectional study

    OpenAIRE

    Kumar, Kanta; Raza, Karim; Nightingale, Peter; Horne, Robert; Chapman, Sarah; Greenfield, Sheila; Gill, Paramjit

    2015-01-01

    Background Rheumatoid arthritis (RA) is a common chronic inflammatory disease causing joint damage, disability, and reduced life expectancy. Highly effective drugs are now available for the treatment of RA. However, poor adherence to drug regimens remains a significant barrier to improving clinical outcomes in RA. Poor adherence has been shown to be linked to patients? beliefs about medicines with a potential impact on adherence. These beliefs are reported to be different between ethnic group...

  14. Glassy carbon electrode modified with multi-walled carbon nanotubes sensor for the quantification of antihistamine drug pheniramine in solubilized systems

    Directory of Open Access Journals (Sweden)

    Rajeev Jain

    2012-02-01

    Full Text Available A sensitive electroanalytical method for quantification of pheniramine in pharmaceutical formulation has been investigated on the basis of the enhanced electrochemical response at glassy carbon electrode modified with multi-walled carbon nanotubes in the presence of sodium lauryl sulfate. The experimental results suggest that the pheniramine in anionic surfactant solution exhibits electrocatalytic effect resulting in a marked enhancement of the peak current response. Peak current response is linearly dependent on the concentration of pheniramine in the range 200–1500 μg/mL with correlation coefficient 0.9987. The limit of detection is 58.31 μg/mL. The modified electrode shows good sensitivity and repeatability. Keywords: Pheniramine, Sodium lauryl sulfate (SLS, Glassy carbon electrode modified with multi-walled carbon nanotubes (GCE-MWCNTs, Solubilized systems, Voltammetric quantification

  15. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William

    2010-01-01

    To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug.......To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug....

  16. Modified cyanobacteria

    Science.gov (United States)

    Vermaas, Willem F J.

    2014-06-17

    Disclosed is a modified photoautotrophic bacterium comprising genes of interest that are modified in terms of their expression and/or coding region sequence, wherein modification of the genes of interest increases production of a desired product in the bacterium relative to the amount of the desired product production in a photoautotrophic bacterium that is not modified with respect to the genes of interest.

  17. Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Goldberg, Lawrence D D; Edwards, Natalie C; Fincher, Contessa; Doan, Quan V; Al-Sabbagh, Ahmad; Meletiche, Dennis M

    2009-09-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that primarily afflicts young adults. Approximately 400,000 people in the United States are affected by MS. Although several forms of MS exist, the most common course is known as relapsing-remitting MS (RRMS), which affects about 85% of MS patients. This form of MS is characterized by relapses of neurologic symptoms followed by periods of recovery. Progression of disease can lead to increasingly severe disability. Since the introduction of immunomodulatory biologic agents, such as interferon betas and glatiramer acetate, treatment has helped to change the course of the disease. Under budgetary constraints, health services payers are challenged to differentiate the economic value of these agents for formulary selection and/or placement. The primary objective of this analysis was to evaluate the 2-year cost-effectiveness of 4 disease modifying drugs (DMDs) used as first-line treatment of RRMS: glatiramer acetate, interferon (IFN) Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b SC injection. An Excel-based model was developed to compare the relative effectiveness and cost components of relapses, disability progression, and DMDs in the treatment of RRMS over a 2-year time horizon. The relative risk reduction (RRR) method was used to compare reduction in relapse rates and disease progression data from pivotal randomized double-blind placebo-controlled clinical trials of the DMDs. RRRs for relapses and disability progression, respectively, were calculated as the relative difference (treatment vs. placebo) in relapse rates and disease progression rates from placebo-controlled clinical trials. These RRRs were applied to the weighted average rates of relapse and number of disability progression steps seen in the placebo arms of the pivotal studies. The evaluation was conducted from the perspective of a U.S. health care payer (only direct medical costs considered

  18. A multifunctional β-CD-modified Fe{sub 3}O{sub 4}@ZnO:Er{sup 3+},Yb{sup 3+} nanocarrier for antitumor drug delivery and microwave-triggered drug release

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hongxia; Cui, Bin, E-mail: cuibin@nwu.edu.cn; Li, Guangming; Wang, Yingsai; Li, Nini; Chang, Zhuguo; Wang, Yaoyu

    2015-01-01

    We constructed a novel core–shell structured Fe{sub 3}O{sub 4}@ZnO:Er{sup 3+},Yb{sup 3+}@(β-CD) nanoparticles used as drug carrier to investigate the loading and controllable release properties of the chemotherapeutic drug etoposide (VP-16). The cavity of β-cyclodextrin is chemically inert, it can store etoposide molecules by means of hydrophobic interactions. The Fe{sub 3}O{sub 4} core and ZnO:Er{sup 3+},Yb{sup 3+} shell functioned successfully for magnetic targeting and up-conversion fluorescence imaging, respectively. In addition, the ZnO:Er{sup 3+},Yb{sup 3+} shell acts as a good microwave absorber with excellent microwave thermal response property for microwave triggered drug release (the VP-16 release of 18% under microwave irradiation for 15 min outclass the 2% within 6 h without microwave irradiation release). The release profile could be controlled by the duration and number of cycles of microwave application. This material therefore promises to be a useful noninvasive, externally controlled drug-delivery system in cancer therapy. - Graphical abstract: We functionalized a multifunctional core–shell Fe{sub 3}O{sub 4}@ZnO:Er{sup 3+},Yb{sup 3+} nanocarriers by adding β-cyclodextrin, which is capable of carrying drug molecules and triggered release of the drug by microwave treatment. - Highlights: • We constructed Fe{sub 3}O{sub 4}@ZnO:Er{sup 3+},Yb{sup 3+}@(β-CD) nanoparticles used as a drug carrier. • The nanoparticles have magnetic and up-conversion fluorescence properties. • The nanoparticles have excellent microwave thermal response property. • The nanocomposite could be a controllable drug release triggered by microwave.

  19. Glassy carbon electrode modified with multi-walled carbon nanotubes sensor for the quantification of antihistamine drug pheniramine in solubilized systems.

    Science.gov (United States)

    Jain, Rajeev; Sharma, Sanjay

    2012-02-01

    A sensitive electroanalytical method for quantification of pheniramine in pharmaceutical formulation has been investigated on the basis of the enhanced electrochemical response at glassy carbon electrode modified with multi-walled carbon nanotubes in the presence of sodium lauryl sulfate. The experimental results suggest that the pheniramine in anionic surfactant solution exhibits electrocatalytic effect resulting in a marked enhancement of the peak current response. Peak current response is linearly dependent on the concentration of pheniramine in the range 200-1500 μg/mL with correlation coefficient 0.9987. The limit of detection is 58.31 μg/mL. The modified electrode shows good sensitivity and repeatability.

  20. A school-based programme for tobacco and alcohol prevention in special education: effectiveness of the modified 'healthy school and drugs' intervention and moderation by school subtype

    NARCIS (Netherlands)

    Turhan, Abdullah; Onrust, Simone; ten Klooster, Peter M.; Pieterse, Marcel E.

    2017-01-01

    AIMS: To test the effectiveness of the Healthy School and Drugs (HSD) programme on tobacco and alcohol use in Dutch secondary special education (SE) schools, and whether this depends upon subtypes of SE schools and the level of implementation. DESIGN: In a quasi-experimental design with baseline and

  1. Modified Extraction-Free Ion-Pair Methods for the Determination of Flunarizine Dihydrochloride in Bulk Drug, Tablets, and Human Urine

    Science.gov (United States)

    Prashanth, K. N.; Basavaiah, K.

    2018-01-01

    Two simple and sensitive extraction-free spectrophotometric methods are described for the determination of flunarizine dihydrochloride. The methods are based on the ion-pair complex formation between the nitrogenous compound flunarizine (FNZ), converted from flunarizine dihydrochloride (FNH), and the acidic dye phenol red (PR), in which experimental variables were circumvented. The first method (method A) is based on the formation of a yellow-colored ion-pair complex (1:1 drug:dye) between FNZ and PR in chloroform, which is measured at 415 nm. In the second method (method B), the formed drug-dye ion-pair complex is treated with ethanolic potassium hydroxide in an ethanolic medium, and the resulting base form of the dye is measured at 580 nm. The stoichiometry of the formed ion-pair complex between the drug and dye (1:1) is determined by Job's continuous variations method, and the stability constant of the complex is also calculated. These methods quantify FNZ over the concentration ranges 5.0-70.0 in method A and 0.5-7.0 μg/mL in method B. The calculated molar absorptivities are 6.17 × 103 and 5.5 × 104 L/mol·cm-1 for method A and method B, respectively, with corresponding Sandell sensitivity values of 0.0655 and 0.0074 μg/cm2. The methods are applied to the determination of FNZ in pure drug and human urine.

  2. Magnetic field assisted μ-solid phase extraction of anti-inflammatory and loop diuretic drugs by modified polybutylene terephthalate nanofibers

    Energy Technology Data Exchange (ETDEWEB)

    Bagheri, Habib, E-mail: bagheri@sharif.edu; Khanipour, Peyman; Asgari, Sara

    2016-08-31

    A magnetic nanocomposite consisting of nanoparticles–polybutylene terephthalate (MNPs–PBT) was electrospun and used as an extracting medium for an on-line μ-solid phase extraction (μ–SPE)–high performance liquid chromatography (HPLC) set–up with an ultraviolet (UV) detection system. Due to the magnetic property of the prepared nanofibers, the whole extraction procedure was implemented under an external magnetic field to enhance the extraction efficiencies. The developed method along with the synthesized nanocomposite were found to be appropriate for the determination of trace levels of selected drugs including furosemide, naproxen, diclofenac and clobetasol propionate in the urine sample. The prepared MNPs-PBT electrospun nanocomposite was characterized using the scanning electron microscopy (SEM), energy dispersive spectroscopy (EDX) and Fourier transform infrared (FT–IR) spectroscopy. The prepared magnetic fibers showed high porosity, which was another driving force for the extraction efficiency enhancement. Major parameters affecting the extraction efficiency of the selected drugs were optimized. The limits of detections (LOD) of the studied drugs were in the range of 0.4–1.6 μg L{sup −1} and the limits of quantification (LOQ) were 1–4 μg L{sup −1} under the optimized conditions. Relative standard deviation (RSD%) for three replicates at three concentration levels of 6, 100 and 400 μg L{sup −1} were 5.9–8.0% while acceptable linear range with two orders of magnitude was obtained (R{sup 2} = 0.99). The method was validated by the determination of the selected drugs in urine samples and the results indicated that this method has sufficient potential for enrichment and determination of the desired drugs in the urine sample. The relative recovery values were found to be in the range of 78–91%. Implementing the developed on–line μ–SPE method under the external magnetic field induction, led to higher extraction efficiencies

  3. Magnetic field assisted μ-solid phase extraction of anti-inflammatory and loop diuretic drugs by modified polybutylene terephthalate nanofibers

    International Nuclear Information System (INIS)

    Bagheri, Habib; Khanipour, Peyman; Asgari, Sara

    2016-01-01

    A magnetic nanocomposite consisting of nanoparticles–polybutylene terephthalate (MNPs–PBT) was electrospun and used as an extracting medium for an on-line μ-solid phase extraction (μ–SPE)–high performance liquid chromatography (HPLC) set–up with an ultraviolet (UV) detection system. Due to the magnetic property of the prepared nanofibers, the whole extraction procedure was implemented under an external magnetic field to enhance the extraction efficiencies. The developed method along with the synthesized nanocomposite were found to be appropriate for the determination of trace levels of selected drugs including furosemide, naproxen, diclofenac and clobetasol propionate in the urine sample. The prepared MNPs-PBT electrospun nanocomposite was characterized using the scanning electron microscopy (SEM), energy dispersive spectroscopy (EDX) and Fourier transform infrared (FT–IR) spectroscopy. The prepared magnetic fibers showed high porosity, which was another driving force for the extraction efficiency enhancement. Major parameters affecting the extraction efficiency of the selected drugs were optimized. The limits of detections (LOD) of the studied drugs were in the range of 0.4–1.6 μg L −1 and the limits of quantification (LOQ) were 1–4 μg L −1 under the optimized conditions. Relative standard deviation (RSD%) for three replicates at three concentration levels of 6, 100 and 400 μg L −1 were 5.9–8.0% while acceptable linear range with two orders of magnitude was obtained (R 2  = 0.99). The method was validated by the determination of the selected drugs in urine samples and the results indicated that this method has sufficient potential for enrichment and determination of the desired drugs in the urine sample. The relative recovery values were found to be in the range of 78–91%. Implementing the developed on–line μ–SPE method under the external magnetic field induction, led to higher extraction efficiencies for the selected

  4. Use and Spending on Biologic Disease-modifying Anti-rheumatic Drugs for Rheumatoid Arthritis among U.S. Medicare Beneficiaries

    Science.gov (United States)

    Yazdany, Jinoos; Tonner, Chris; Schmajuk, Gabriela

    2015-01-01

    Objectives Biologic therapies have assumed an important role in treating rheumatoid arthritis (RA). We sought to investigate use, spending, and patient cost-sharing for Medicare beneficiaries using biologic drugs for RA, comparing patients exposed to minimal cost-sharing because of a Part D low-income subsidy (LIS) to those facing substantial out-of-pocket costs (OOP). Methods We performed a retrospective, nationwide study using 2009 Medicare claims for a 5% random sample of beneficiaries with RA who had at least one RA drug dispensed. We analyzed biologic drug utilization and costs across the Part B (medical benefit) and Part D (pharmacy benefit) programs by LIS status using multinomial regression. We also projected OOP costs as the Affordable Care Act (ACA) mandates closure of the Part D coverage gap by 2020. Results Among 6932 beneficiaries, 1812 (26.1%) received a biologic drug. LIS beneficiaries were significantly more likely to obtain Part D home-administered biologics (RRR 2.98, 95% CI 2.50–3.56), while non-LIS beneficiaries were less likely to receive Part D biologics (RRR 0.58, 95% CI 0.48–0.69). OOP costs in Part D were lower, as expected, for LIS beneficiaries ($72 vs. $3,751/year for non-LIS). Non-LIS beneficiaries had lower costs for Part B facility-administered biologics (range $0–$2,584) than for Part D home-administered biologics. ACA reforms will narrow OOP differences between Part D and B for non-LIS beneificiaries. Conclusions In contrast to LIS beneficiaries who receive mostly Part D home-administered biologic DMARDs, non-subsidized beneficiaries have significant cost-based incentives to obtain facility-administered biologic DMARDs through Part B. The ACA will result in only slightly lower costs for Part D biologic drugs for these beneficiaries. PMID:25776035

  5. A MULTICENTER, BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF THE SYMPTOM- AND STRUCTURE-MODIFYING EFFET OF ALFLUTOP IN PATIENTS WITH KNEE OSTEOARTHRITIS. REPORT 2: THE ASSESSMENT OF THE STRUCTURE-MODIFYING EFFECT OF THE DRUG

    Directory of Open Access Journals (Sweden)

    L. I. Alekseeva

    2014-01-01

    Full Text Available Objective. To evaluate the symptom- and structure-modifying effect of Alflutop compared to placebo (PL in patients with knee osteoarthritis (OA. Material and methods. The study included 90 patients with knee OA (according to the criteria of the Russian Association of Rheumatologists at the stage 2–3 (according to the Kellgren-Lawrence scale; pain score when walk- ing ≥ 40 mm (assessed using the visual analog scale. All the patients provided an informed consent. The patients were randomly divided into two groups: group 1 (n=45 received an intramuscular injection of 1 mL Alflutop for 20 days with 6-month intervals for 2 years (a total of 4 courses for 2 years; group 2 (n=45 received an injection of PL (iso- tonic sodium chloride solution in the same way. Ibuprofen at a dose of 600–1200 mg/day was administered as concomitant therapy. To evaluate the structure-modifying effect of Alflutop, X-ray of the knee joint was performed at the beginning and end of the study; the level of biochemical markers (CTX-II and COMP was determined at the beginning, after 3 months, and at the end of the study. A statistical analysis was performed using the Statistica 10 software package.Results. After the 2-year follow-up, a statistically significant negative trend was detected less frequently in the group of patients treated with Alflutop compared to the PL group (6.1 and 38.4%, respectively. The statistically significant delay in joint space narrowing was observed in patients who received Alflutop in contrast to patients who received PL (the numerical score of the joint space, the Wilcoxon test; p=0.0003. An increase in osteo- phyte size was observed in 72% of the patients receiving PL, and only in 27% of the patients receiving Alflutop (medial and lateral osteophytes of the femoral bone, the Wilcoxon test; p=0.0078; medial and lateral osteophytes of the shin bone, the Wilcoxon test; p=0.0001 and p=0.0039, respective- ly. Augmentation of subchondral

  6. Clinical and laboratory assessment of a combination of drugs with radiation. Coordinated programme on improvement in radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    Bleehen, N.

    1982-01-01

    Applications were clinically studied of misonidazole (MISO) as a hypoxic cell radiosensitizer with pharmacokinetic studies. Work with desmethylmisonidazole was focused on its penetration into the CNS because its low lipophilicity would predict poorer access than MISO. Laboratory work was focused on the interaction of hyperthermia with drugs. Cytotoxicity of MISO induced by hyperthermia was studied. Heat response following hypoxic pretreatment with MISO of EMT6 spheroids showed marked enhancement of subsequent heat killing dependent on the duration of the hypoxic pretreatment. The effect was studied in vitro of preheat temperature at modest temperatures (39 to 43 0 C) on thermal tolerance and subsequent hyperthermic (43 to 44 0 C) interaction with bleomycin, adriamycin and BCNU. Interaction between several cytotoxic drugs and two potentially critical normal tissues, skin and bone marrow was studied in the mouse. No increase in the heat reaction in the skin of the mouse foot was observed following single injections of adriamycin, bleomycin or 5 daily doses of bleomycin together with a single heat treatment. Single doses of BCNU and CTX increased the heat reaction. The radioprotector WR2721 failed to protect against either the heat or heat drug reactions from CTX and BCNU

  7. Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery: epigenetic regulation of the hypoxic response via hypoxia-inducible factor and histone modifying enzymes.

    Science.gov (United States)

    Mimura, Imari; Tanaka, Tetsuhiro; Wada, Youichiro; Kodama, Tatsuhiko; Nangaku, Masaomi

    2011-01-01

    The hypoxia response regulated primarily by hypoxia-inducible factor (HIF) influences metabolism, cell survival, and angiogenesis to maintain biological homeostasis. In addition to the traditional transcriptional regulation by HIF, recent studies have shown that epigenetic modulation such as histone methylation, acetylation, and DNA methylation could change the regulation of the response to hypoxia. Eukaryotic chromatin is known to be modified by multiple post-translational histone methylation and demethylation, which result in the chromatin conformation change to adapt to hypoxic stimuli. Interestingly, some of the histone demethylase enzymes, which have the Jumonji domain-containing family, require oxygen to function and are induced by hypoxia in an HIF-1-dependent manner. Recent studies have demonstrated that histone modifiers play important roles in the hypoxic environment such as that in cancer cells and that they may become new therapeutic targets for cancer patients. It may lead to finding a new therapy for cancer to clarify a new epigenetic mechanism by HIF and histone demethylase such as JMJD1A (KDM3A) under hypoxia.

  8. Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects.

    Science.gov (United States)

    Song, Zhiwang; Lin, Yun; Zhang, Xia; Feng, Chan; Lu, Yonglin; Gao, Yong; Dong, Chunyan

    2017-01-01

    Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin α v β 3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer.

  9. Study and comparison of the meta cognitive-emotional processing and drug therapy in modifying emotional, cognitive and social skills in bipolar disorders

    Directory of Open Access Journals (Sweden)

    fatemeh bahrami

    2009-11-01

    Full Text Available Psychotherapy for bipolor disorder has been very much neglected. The aim of this study was to determine and compare the meta cognitive, emotional processing training (MEPT with medical and standard therapy (drug in increasing emotional, cognitive and social skills, of the patients with bipolar disorders. Materials and Methods: This semi experimental study with control group was carried out on 32 females in the 16-40 age bracket, diagnosed with bipolar disorder by means of DSM - IV –R criteria selected among referrals from Isfahan hospitals and psychology clinics. One group randomly received medical therapy plus MEPT. The second group (control group received standard drug therapy. Data gathering instruments were a semi – structural interview based on DSM – IV – R criteria and the following questionnaires: Mania (Bech, et al, 1979, Depression (Hamilton, 1980, Emotional intelligence (Cooper, 1999, Self – control (Rosenbaum, 1980, Insigt (David, et al, 1992, Social function (Hurry, et al, 1983. And the Aconomic, social, cultural questionnaire was used to control social ststus of the subjects. this questionnaire was made by the researcher. Results: The MEPT method influenced on increasing all of the emotional skills, sub scales and total scales. And also influenced on cognitive scales such as: dysfunctional thought, (p=0. 000, insight (p=0. 05, self – control (p=0. 000. Social skills could be increased (p=0. 02 by use of MEPT. Conclusion: Using pschological treatment in addition to pharmacotherapy increases treatment efficay. Therefor an educational program about MEPT is necessary for therapists.

  10. Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement

    Directory of Open Access Journals (Sweden)

    Li CY

    2016-11-01

    Full Text Available ChunYan Li,1 ZhiGang Huang,2 ZheShuo Liu,1 LiQian Ci,3 ZhePeng Liu,3 Yu Liu,2 XueYing Yan,1 WeiYue Lu2 1School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 2Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 3School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China Abstract: Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050, good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA assay of

  11. Formas farmacêuticas de liberação modificada: polímeros hidrifílicos Modified release of drug delivery systems: hydrophilic polymers

    Directory of Open Access Journals (Sweden)

    Carla Martins Lopes

    2005-06-01

    Full Text Available Os sistemas de liberação de fármacos são parte integrante da investigação farmacêutica. A maioria dos sistemas de liberação oral de fármacos é baseada em matrizes poliméricas. Nas duas décadas passadas, as matrizes hidrofílicas tornaram-se muito populares na formulação de formas farmacêuticas de liberação modificada. A escolha do polímero hidrofílico na formulação da matriz pode fornecer uma combinação apropriada dos mecanismos de intumescimento, de dissolução ou de erosão e determinam a cinética de liberação in vitro. As matrizes de intumescimento são sistemas monolíticos preparados pela compressão de mistura de um polímero hidrofílico e de um fármaco. Elas representam sistemas da liberação em que os vários mecanismos podem ser adaptados ao programa de liberação. O sucesso desses sistemas está relacionado com a tecnologia de fabricação e com as características físicas e físico-químicas do polímero, responsáveis pelo mecanismo de liberação.Drug delivery systems (DDS became an integral part of pharmaceutical research. The majority of oral DDS are matrix-based systems. Hydrophilic matrices for the past two decades have been popular in the formulation of controlled release solid dosage forms. Swellable matrices are monolithic systems prepared by compression of a powdered mixture of a hydrophilic polymer and a drug. They represent a delivery system in which various mechanisms can be adapted to the delivery program. Their success is linked to the established tabletting technology of manufacture. The choice of the hydrophilic polymer in the matrix formulation can provide an appropriate combination of swelling, dissolution or erosion mechanisms to evaluate in vitro release kinetics.

  12. A school-based programme for tobacco and alcohol prevention in special education: effectiveness of the modified 'healthy school and drugs' intervention and moderation by school subtype.

    Science.gov (United States)

    Turhan, Abdullah; Onrust, Simone A; Ten Klooster, Peter M; Pieterse, Marcel E

    2017-03-01

    To test the effectiveness of the Healthy School and Drugs (HSD) programme on tobacco and alcohol use in Dutch secondary special education (SE) schools, and whether this depends upon subtypes of SE schools and the level of implementation. In a quasi-experimental design with baseline and post-treatment follow-up, 363 students were allocated arbitrarily or depending on teacher motivation to either intervention condition (n = 205) or usual curriculum (n = 158). Thirteen secondary SE schools spread throughout the Netherlands. Participants were recruited during the autumn of 2013 from three school subtypes: SE for adolescents with intellectual/physical disabilities (SEI; n = 13), behavioural/emotional difficulties (SEB; n = 136) and learning disabilities/developmental disorders (SEL; n = 214). Self-reported life-time smoking prevalence and life-time drinking frequency as outcomes, and school subtype (SEL/SEB) and implementation fidelity (high/low) as moderators. No significant differences were found at follow-up in life-time smoking [odds ratio (OR) = 1.52; 95% confidence interval (CI) = 0.74-3.12] and drinking frequency (d = 0.01; 95% CI = -0.16 to 0.18). Interaction analyses revealed adverse effects in SEB students for alcohol use (d = 0.43; 95% CI = 0.16-0.69). Effect on tobacco refusal self-efficacy was moderated positively by implementation fidelity (d = 0.35; 95% CI = 0.07-0.63). The Healthy School and Drugs programme adapted for secondary special education in the Netherlands lacked clear evidence for effects on all outcomes. This pilot study suggests further that, within special education, substance use interventions may need to be targeted at school subtypes, as these may have harmful effects among students with behavioural difficulties. Finally, limited evidence was found that programme effectiveness may depend upon implementation fidelity. © 2016 Society for the Study of Addiction.

  13. Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

    Science.gov (United States)

    Cheung, E. V.; Tidball, J. G.

    2003-01-01

    OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

  14. Preparation of water stable methyl-modified metal-organic framework-5/polyacrylonitrile composite nanofibers via electrospinning and their application for solid-phase extraction of two estrogenic drugs in urine samples.

    Science.gov (United States)

    Asiabi, Mina; Mehdinia, Ali; Jabbari, Ali

    2015-12-24

    The nanofibers of methyl-modified metal-organic framework-5/polyacrylonitrile composite (CH3MOF-5/PAN) were successfully synthesized and used as a solid-phase extraction (SPE) sorbent for pre-concentration of two estrogenic drugs, levonorgestrel and megestrol acetate, in urine samples. A simple, cheap and accessible electrospinning method was employed to prepare a water stable CH3MOF-5/PAN composite. The nanofibers were packed into the mini-disc cartridges to be used as SPE devices. They were also characterized by scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, X-ray diffraction and N2 adsorption-desorption experiments. The effects of different parameters influencing the extraction efficiency including the type of eluent and its volume, the amount of the sorbent, pH, the ionic strength, the sample volume and the reusability of the sorbent were investigated and optimized. Under the optimized conditions, the linearity varied in range of 0.05-100μgL(-1) with R(2) values higher than 0.999. The limit of detection for both of the analytes was 0.02μgL(-1). The applicability of the method was examined by analyzing the analytes in the urine samples. The recovery of the analytes varied in the range of 82.8-94.8% which shows capability of the method for the determination of the drugs in the urine samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan.

    Science.gov (United States)

    Takeuchi, Tsutomu; Ishida, Kota; Shiraki, Katsuhisa; Yoshiyasu, Takashi

    2018-01-01

    Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

  16. 21 CFR 184.1287 - Enzyme-modified fats.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Enzyme-modified fats. 184.1287 Section 184.1287... Listing of Specific Substances Affirmed as GRAS § 184.1287 Enzyme-modified fats. (a) Enzyme-modified refined beef fat, enzyme-modified butterfat, and enzyme-modified steam-rendered chicken fat are prepared...

  17. Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.

    Science.gov (United States)

    Liang, Po-Chin; Chen, Yung-Chu; Chiang, Chi-Feng; Mo, Lein-Ray; Wei, Shwu-Yuan; Hsieh, Wen-Yuan; Lin, Win-Li

    2016-01-01

    In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.

  18. Novel Interactions between Gut Microbiome and Host Drug-Processing Genes Modify the Hepatic Metabolism of the Environmental Chemicals Polybrominated Diphenyl Ethers

    Energy Technology Data Exchange (ETDEWEB)

    Li, Cindy Yanfei; Lee, Soowan; Cade, Sara; Kuo, Li-Jung; Schultz, Irvin R.; Bhatt, Deepak K.; Prasad, Bhagwat; Bammler, Theo K.; Cui, Julia Yue

    2017-09-01

    The gut microbiome is a novel frontier in xenobiotic metabolism. Polybrominated diphenyl ethers (PBDEs), especially BDE-47 and BDE-99, are among the most abundant and persistent environmental contaminants that produce a variety of toxicities. Little is known about how the gut microbiome affects the hepatic metabolism of PBDEs and the PBDE-mediated regulation of drug-processing genes (DPGs) in vivo. The goal of this study was to determine the role of gut microbiome in modulating the hepatic biotransformation of PBDEs. Nine-week-old male C57BL/6J conventional (CV) or germ free (GF) mice were treated with vehicle, BDE-47 or BDE-99 (100 μmol/kg) for four days. Following BDE-47 treatment, GF mice had higher level of 5-OH-BDE-47 but lower levels of 4 other metabolites in liver than CV mice; whereas following BDE-99 treatment, GF mice had lower levels of 4 minor metabolites in liver than CV mice. RNA- Seq demonstrated that the hepatic expression of DPGs was regulated by both PBDEs and enterotypes. Under basal condition, the lack of gut microbiome up-regulated the Cyp2c subfamily but down-regulated the Cyp3a subfamily. Following PBDE exposure, certain DPGs were differentially regulated by PBDEs in a gut microbiome-dependent manner. Interestingly, the lack of gut microbiome augmented PBDE-mediated up- regulation of many DPGs, such as Cyp1a2 and Cyp3a11 in mouse liver, which was further confirmed by targeted metabolomics. The lack of gut microbiome also augmented the Cyp3a enzyme activity in liver. In conclusion, our study has unveiled a novel interaction between gut microbiome and the hepatic biotransformation of PBDEs.

  19. Transferrin receptor antibody-modified α-cobrotoxin-loaded nanoparticles enable drug delivery across the blood–brain barrier by intranasal administration

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lin; Zhang, Xiangyi [Zhejiang University School of Medicine, Department of Pharmacology, First Affiliated Hospital (China); Li, Wuchao [ZheJiang Chinese Medical University, College of Pharmaceutical Science (China); Sun, Haozhen; Lou, Yan; Zhang, Xingguo, E-mail: xgzhang@zju.edu.cn [Zhejiang University School of Medicine, Department of Pharmacology, First Affiliated Hospital (China); Li, Fanzhu [ZheJiang Chinese Medical University, College of Pharmaceutical Science (China)

    2013-11-15

    A novel drug carrier for brain delivery, maleimide–poly(ethyleneglycol)–poly(lactide) (maleimide–PEG–PLA) nanoparticles (NPs) conjugated with mouse–anti-rat monoclonal antibody OX26 (OX26–NPs), was developed and its brain delivery property was evaluated. The diblock copolymers of maleimide–PEG–PLA were synthesized and applied to α-cobrotoxin (αCT)-loaded NPs which were characterized by transmission electron micrograph imaging, Fourier-transform IR, and X-ray diffraction. The NPs encapsulating αCT had a round and vesicle-like shape with a mean diameter around 100 nm, and the OX26 had covalently conjugated to the surface of NPs. MTT studies in brain microvascular endothelial cells (BMEC) revealed a moderate decrease in the cell viability of αCT, when incorporated in OX26–NPs compared to free αCT in solution. A higher affinity of the OX26–αCT–NPs to the BMEC was shown in comparison to αCT–NPs. Then, OX26–αCT–NPs were intranasally (i.n.) administered to rats, and αCT in the periaqueductal gray was monitored for up to 480 min using microdialysis technique in free-moving rats, with i.n. αCT–NPs, i.n. OX26–αCT–NPs, intramuscular injection (i.m.) αCT–NPs, and i.m. OX26–αCT–NPs. The brain transport results showed that the corresponding absolute bioavailability (F{sub abs}) of i.n. OX26–αCT–NPs were about 125 and 155 % with i.n. αCT–NPs and i.m. OX26–αCT–NPs, respectively, and it was found that both the C{sub max} and AUC of the four groups were as follows: i.n. OX26–αCT–NPs > i.n. αCT–NPs > i.m. OX26–αCT–NPs > i.m. αCT–NPs, while αCT solution, as control groups, could hardly enter the brain. These results indicated that OX26–NPs are promising carriers for peptide brain delivery.

  20. Transferrin receptor antibody-modified α-cobrotoxin-loaded nanoparticles enable drug delivery across the blood-brain barrier by intranasal administration

    Science.gov (United States)

    Liu, Lin; Zhang, Xiangyi; Li, Wuchao; Sun, Haozhen; Lou, Yan; Zhang, Xingguo; Li, Fanzhu

    2013-11-01

    A novel drug carrier for brain delivery, maleimide-poly(ethyleneglycol)-poly(lactide) (maleimide-PEG-PLA) nanoparticles (NPs) conjugated with mouse-anti-rat monoclonal antibody OX26 (OX26-NPs), was developed and its brain delivery property was evaluated. The diblock copolymers of maleimide-PEG-PLA were synthesized and applied to α-cobrotoxin (αCT)-loaded NPs which were characterized by transmission electron micrograph imaging, Fourier-transform IR, and X-ray diffraction. The NPs encapsulating αCT had a round and vesicle-like shape with a mean diameter around 100 nm, and the OX26 had covalently conjugated to the surface of NPs. MTT studies in brain microvascular endothelial cells (BMEC) revealed a moderate decrease in the cell viability of αCT, when incorporated in OX26-NPs compared to free αCT in solution. A higher affinity of the OX26-αCT-NPs to the BMEC was shown in comparison to αCT-NPs. Then, OX26-αCT-NPs were intranasally (i.n.) administered to rats, and αCT in the periaqueductal gray was monitored for up to 480 min using microdialysis technique in free-moving rats, with i.n. αCT-NPs, i.n. OX26-αCT-NPs, intramuscular injection (i.m.) αCT-NPs, and i.m. OX26-αCT-NPs. The brain transport results showed that the corresponding absolute bioavailability ( F abs) of i.n. OX26-αCT-NPs were about 125 and 155 % with i.n. αCT-NPs and i.m. OX26-αCT-NPs, respectively, and it was found that both the C max and AUC of the four groups were as follows: i.n. OX26-αCT-NPs > i.n. αCT-NPs > i.m. OX26-αCT-NPs > i.m. αCT-NPs, while αCT solution, as control groups, could hardly enter the brain. These results indicated that OX26-NPs are promising carriers for peptide brain delivery.

  1. Plain radiography or magnetic resonance imaging (MRI): Which is better in assessing outcome in clinical trials of disease-modifying osteoarthritis drugs? Summary of a debate held at the World Congress of Osteoarthritis 2014.

    Science.gov (United States)

    Eckstein, Felix; Le Graverand, Marie-Pierre Hellio

    2015-12-01

    Osteoarthritis (OA) is the most common disease of synovial joints and currently lacks treatment options that modify structural pathology. Imaging is ideally suited for directly evaluating efficacy of disease-modifying OA drugs (DMOADs) in clinical trials, with plain radiography and MRI being most often applied. The current article is based on a debate held on April 26, 2014, at the World Congress of Osteoarthritis: The authors were invited to contrast strengths and limitations of both methods, highlighting scientific evidence on reliability, construct-validity, and correlations with clinical outcome, and comparing their sensitivity to change in knee OA and sensitivity to DMOAD treatment. The authors concluded that MRI provides more comprehensive information on articular tissues pathology, and that implementation of radiography in clinical trials remains a challenge. However, neither technique has thus far been demonstrated to be strongly superior over the other; for the time being it therefore appears advisable to use both in parallel in clinical trials, to provide more evidence on their relative performance. Radiographic JSW strongly depends on adequate positioning; it is not specific to cartilage loss but also to the meniscus. MRI provides somewhat superior sensitivity to change compared with the commonly used non-fluoroscopic radiographic acquisition protocols, and has recently provided non-location-dependent measures of cartilage thickness loss and gain, which are potentially more sensitive in detecting DMOAD effects than radiographic JSW or region-specific MRI. Non-location-dependent measures of cartilage thickness change should thus be explored further in context of anabolic and anti-catabolic DMOADs. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Long-Term Outcomes in Puerto Ricans with Rheumatoid Arthritis (RA) Receiving Early Treatment with Disease-Modifying Anti-Rheumatic Drugs using the American College of Rheumatology Definition of Early RA.

    Science.gov (United States)

    Varela-Rosario, Noemí; Arroyo-Ávila, Mariangelí; Fred-Jiménez, Ruth M; Díaz-Correa, Leyda M; Pérez-Ríos, Naydi; Rodríguez, Noelia; Ríos, Grissel; Vilá, Luis M

    2017-01-01

    Early treatment of rheumatoid arthritis (RA) results in better long-term outcomes. However, the optimal therapeutic window has not been clearly established. To determine the clinical outcome of Puerto Ricans with RA receiving early treatment with conventional and/or biologic disease-modifying anti-rheumatic drugs (DMARDs) based on the American College of Rheumatology (ACR) definition of early RA. A cross-sectional study was performed in a cohort of Puerto Ricans with RA. Demographic features, clinical manifestations, disease activity, functional status, and pharmacotherapy were determined. Early treatment was defined as the initiation of DMARDs (conventional and/or biologic) in less than 6 months from the onset of symptoms attributable to RA. Patients who received early (disease duration was 14.9 years and 337 (87.0%) patients were women. One hundred and twenty one (31.3%) patients received early treatment. In the multivariate analysis adjusted for age and sex, early treatment was associated with better functional status, lower probability of joint deformities, intra-articular injections and joint replacement surgeries, and lower scores in the physician's assessments of global health, functional impairment and physical damage of patients. Using the ACR definition of early RA, this group of patients treated with DMARDs within 6 months of disease had better long-term outcomes with less physical damage and functional impairment.

  3. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  4. Antiretroviral therapeutic drug monitoring

    African Journals Online (AJOL)

    Winnie

    GENERAL PRINCIPLES OF TDM. The vast majority of drugs used in clinical practice do not require TDM. It is far easier for clinicians to adopt a 'one size fits all' approach to dosing. Alternatively doses may be modified according to response. However, with some drugs this will result in high rates of toxicity, or suboptimal ...

  5. 21 CFR 184.1063 - Enzyme-modified lecithin.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Enzyme-modified lecithin. 184.1063 Section 184.1063... Listing of Specific Substances Affirmed as GRAS § 184.1063 Enzyme-modified lecithin. (a) Enzyme-modified... Lysolecithin Content of Enzyme-Modified Lecithin: Method I,” dated 1985, which is incorporated by reference in...

  6. Interfacial Modifiers

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Ina; French, Roger H.

    2018-03-19

    Our project objective in the first and only Budget Period was to demonstrate the potential of nm-scale organofunctional silane coatings as a method of extending the lifetime of PV materials and devices. Specifically, the target was to double the lifetime performance of a laminated Cu(In,Ga)Se2 (CIGS) cell under real-world and accelerated aging exposure conditions. Key findings are that modification of aluminum-doped zinc oxide (AZO) films (materials used as transparent conductive oxide (TCO) top contacts) resulted in decreased degradation of optical and electrical properties under damp heat (DH) exposure compared to un-modified AZO. The most significant finding is that modification of the AZO top contact of full CIGS devices resulted in significantly improved properties under DH exposure compared to un-modified devices, by a factor of 4 after 1000 h. Results of this one-year project have demonstrated that surface functionalization is a viable pathway for extending the lifetime of state-of-the-art CIGS devices.

  7. Association between use of disease-modifying antirheumatic drugs and diabetes in patients with ankylosing spondylitis, rheumatoid arthritis, or psoriasis/psoriatic arthritis: a nationwide, population-based cohort study of 84,989 patients

    Directory of Open Access Journals (Sweden)

    Chen HH

    2017-05-01

    Full Text Available Hsin-Hua Chen,1–7 Der-Yuan Chen,1–6 Chi-Chen Lin,1,2 Yi-Ming Chen,1–4 Kuo-Lung Lai,3,4 Ching-Heng Lin1 1Department of Medical Research, Taichung Veterans General Hospital, 2Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, 3School of Medicine, National Yang-Ming University, Taipei, 4Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 5School of Medicine, Chung-Shan Medical University, 6Department of Medical Education, Taichung Veterans General Hospital, Taichung, 7Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan Purpose: The aim of this study is to investigate the association between the use of disease-modifying antirheumatic drugs (DMARDs and diabetes mellitus (DM in patients with ankylosing spondylitis (AS, rheumatoid arthritis (RA, or psoriasis/psoriatic arthritis (PS/PSA.Patients and methods: This retrospective cohort study used a nationwide, population-based administrative database to enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti-tumor necrosis factor (anti-TNF drugs or nonbiologic DMARDs. Multivariable analysis was used to estimate the effect of different therapies on the risk of DM.Results: The incidence rates of DM per 1,000 person-years were 8.3 for users of anti-TNF drugs, 13.3 for users of cyclosporine (CSA, 8.4 for users of hydroxychloroquine (HCQ, and 8.1 for users of other nonbiologic DMARDs. Compared with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios (aHRs for DM were significantly lower for those who used anti-TNF drugs with HCQ (aHR: 0.49, 95% confidence interval [CI]: 0.36–0.66 and those who used HCQ alone (aHR: 0.70, 95% CI: 0.63–0.78, but not for those who used anti-TNFs without HCQ (aHR: 1.23, 95% CI: 0.94–1.60 or CSA (aHR: 1.14, 95% CI: 0.77–1

  8. Drug Facts

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    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  9. Drug Facts

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    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  10. Drug Facts

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    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  11. Selection of knee radiographs for trials of structure-modifying drugs in patients with knee osteoarthritis: a prospective, longitudinal study of Lyon Schuss knee radiographs with the definition of adequate alignment of the medial tibial plateau.

    Science.gov (United States)

    Conrozier, Thierry; Mathieu, Pierre; Piperno, Muriel; Favret, Huguette; Colson, Frédéric; Vignon, Martine; Conrozier, Sylvie; Vignon, Eric

    2005-05-01

    The quality of medial tibial plateau (MTP) alignment, which is assessed by measuring the distance between the anterior and posterior margins (intermargin distance [IMD]) of the tibial plateau, and the reproducibility of alignment in serial radiographs are suggested to be key elements in determining the accuracy and sensitivity to change in knee radiographs in patients with tibiofemoral osteoarthritis (OA). We evaluated the influence of both MTP alignment and radiograph superimposition on the sensitivity to change in radiographic joint space narrowing (JSN) in knee OA. The study group comprised 106 patients with knee pain (73 with OA). Lyon schuss radiographic images of the knee were obtained twice (at baseline [month 0] and 12 months later), using a standardized radiographic procedure. Computerized measurement of the IMD for the assessment of MTP alignment was compared with the grading of MTP alignment by 2 observers using a 5-point scale (excellent, good, fair, poor, bad). To obtain the rate of JSN, computerized measurement of the joint space width was performed at month 0 and month 12. The sensitivity of the joint space width to change over 1 year was evaluated by the standardized response mean (SRM). The mean (+/-SD) IMD was 1.2 +/- 0.9 mm. The correlation between scoring and computer measurement of MTP alignment was highly significant. The cutoff value for satisfactory alignment (excellent or good) was an IMD of 1.2 mm at month 0 and/or month 12. The quality of MTP alignment at both baseline and the end point highly influences the sensitivity to change in radiographic JSN in knee OA. To obtain relevant data, only radiographs showing an IMD of modifying OA drugs.

  12. Tocilizumab in patients with active rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs or tumor necrosis factor inhibitors: subanalysis of Spanish results of an open-label study close to clinical practice.

    Science.gov (United States)

    Álvaro-Gracia, José M; Fernández-Nebro, Antonio; García-López, Alicia; Guzmán, Manuel; Blanco, Francisco J; Navarro, Francisco J; Bustabad, Sagrario; Armendáriz, Yolanda; Román-Ivorra, José A

    2014-01-01

    To analyze the Spanish experience in an international study which evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice setting. Subanalysis of 170 patients with RA from Spain who participated in a phase IIIb, open-label, international clinical trial. Patients presented inadequate response to DMARDs or TNFis. They received 8mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20 weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was placed on differences between failure to a DMARD or to a TNFi and the need to switch to tocilizumab with or without a washout period in patients who had previously received TNFi. The most common adverse events were infections (25%), increased total cholesterol (38%) and transaminases (15%). Five patients discontinued the study due to an adverse event. After six months of tocilizumab treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A higher proportion of TNFi-naive patients presented an ACR20 response: 76% compared to 64% in the TNFi group with previous washout and 66% in the TNFi group without previous washout. Safety results were consistent with previous results in patients with RA and an inadequate response to DMARDs or TNFis. Tocilizumab is more effective in patients who did not respond to conventional DMARDs than in patients who did not respond to TNFis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Drug Addiction

    Science.gov (United States)

    ... attempt to stop taking the drug Recognizing unhealthy drug use in family members Sometimes it's difficult to ... sold to support drug use Recognizing signs of drug use or intoxication Signs and symptoms of drug ...

  14. Drug Allergy

    Science.gov (United States)

    ... Seizure Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days ... reaction the first time you take the drug. Drugs commonly linked to allergies Although any drug can ...

  15. Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70

    Science.gov (United States)

    Orme, Michelle E; MacGilchrist, Katherine S; Mitchell, Stephen; Spurden, Dean; Bird, Alex

    2012-01-01

    Background Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with suboptimal response or intolerance to conventional DMARDs. The objective of this systematic review and meta-analysis was to compare the relative efficacy of EU-licensed bDMARD combination therapy or monotherapy for patients intolerant of or contraindicated to continued methotrexate. Methods Comprehensive, structured literature searches were conducted in Medline, Embase, and the Cochrane Library, as well as hand-searching of conference proceedings and reference lists. Phase II or III randomized controlled trials reporting American College of Rheumatology (ACR) criteria scores of 20, 50, and 70 between 12 and 30 weeks’ follow-up and enrolling adult patients meeting ACR classification criteria for rheumatoid arthritis previously treated with and with an inadequate response to conventional DMARDs were eligible. To estimate the relative efficacy of treatments whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using fixed and random-effects, logit-link models fitted to the binomial ACR 20/50/70 trial data. Results The systematic review identified 10,625 citations, and after a review of 2450 full-text papers, there were 29 and 14 eligible studies for the combination and monotherapy meta-analyses, respectively. In the combination analysis, all licensed bDMARD combinations had significantly higher odds of ACR 20/50/70 compared to DMARDs alone, except for the rituximab comparison, which did not reach significance for the ACR 70 outcome (based on the 95% credible interval). The etanercept combination was significantly better than the tumor necrosis factor-α inhibitors adalimumab and infliximab in improving ACR 20/50/70 outcomes, with no significant differences between the etanercept combination and certolizumab pegol or tocilizumab. Licensed-dose etanercept, adalimumab

  16. Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70

    Directory of Open Access Journals (Sweden)

    Orme ME

    2012-12-01

    Full Text Available Michelle E Orme,1 Katherine S MacGilchrist,2 Stephen Mitchell,2 Dean Spurden,3 Alex Bird31Icera Consulting, Swindon, Wiltshire, UK; 2Systematic Review Department, Abacus International, Bicester, Oxfordshire, UK; 3Pfizer UK Limited, Tadworth, Surrey, UKBackground: Biologic disease-modifying antirheumatic drugs (bDMARDs extend the treatment choices for rheumatoid arthritis patients with suboptimal response or intolerance to conventional DMARDs. The objective of this systematic review and meta-analysis was to compare the relative efficacy of EU-licensed bDMARD combination therapy or monotherapy for patients intolerant of or contraindicated to continued methotrexate.Methods: Comprehensive, structured literature searches were conducted in Medline, Embase, and the Cochrane Library, as well as hand-searching of conference proceedings and reference lists. Phase II or III randomized controlled trials reporting American College of Rheumatology (ACR criteria scores of 20, 50, and 70 between 12 and 30 weeks' follow-up and enrolling adult patients meeting ACR classification criteria for rheumatoid arthritis previously treated with and with an inadequate response to conventional DMARDs were eligible. To estimate the relative efficacy of treatments whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using fixed and random-effects, logit-link models fitted to the binomial ACR 20/50/70 trial data.Results: The systematic review identified 10,625 citations, and after a review of 2450 full-text papers, there were 29 and 14 eligible studies for the combination and monotherapy meta-analyses, respectively. In the combination analysis, all licensed bDMARD combinations had significantly higher odds of ACR 20/50/70 compared to DMARDs alone, except for the rituximab comparison, which did not reach significance for the ACR 70 outcome (based on the 95% credible interval. The etanercept combination was

  17. Drug Facts

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    Full Text Available ... some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely ... So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug ...

  18. Drug allergies

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    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  19. Drug Facts

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    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  20. Drug Facts

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    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  1. Drug Facts

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    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  2. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  3. Drug Facts

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    Full Text Available ... and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ... Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use ...

  4. Drugs ID Obesity

    African Journals Online (AJOL)

    a new attitude to eating. Adjunctive measures aimed at modifying behaviour, such as psychotherapy and group therapy, may help in individual cases. Psychological factors in response to stress would appear to be the basis of some cases of obesity, but the use of psychotropic drugs is limited and for specific indications only.

  5. MWCNTs/Cu(OH)2 nanoparticles/IL nanocomposite modified glassy carbon electrode as a voltammetric sensor for determination of the non-steroidal anti-inflammatory drug diclofenac

    International Nuclear Information System (INIS)

    Arvand, Majid; Gholizadeh, Tahereh M.; Zanjanchi, Mohammad Ali

    2012-01-01

    This paper describes the development and utilization of a new nanocomposite consisting of Cu(OH) 2 nanoparticles, hydrophobic ionic liquid 1-ethyl-3-methylimidazolium hexafluorophosphate (EMIMPF 6 ) and multiwalled carbon nanotubes for glassy carbon electrode modification. The nanocomposite was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM) along with energy-dispersive X-ray spectroscopy (EDX). The modified electrode was used for electrochemical characterization of diclofenac. Using differential pulse voltammetry, the prepared sensor showed good sensitivity and selectivity with low overpotential for the determination of diclofenac in the range from 0.18 to 119 μM, with a detection limit of 0.04 μM. Electrochemical studies suggested that the MWCNTs/Cu(OH) 2 nanoparticles/IL nanocomposite modified electrode provided a synergistic augmentation on the voltammetric behavior of electrochemical oxidation of diclofenac, which was indicated by the improvement of anodic peak current. Highlights: ► This work examines oxidation of diclofenac at a nanocomposite modified electrode. ► The salient feature of this electrode is large diffusion coefficient. ► The proposed electrode decreased overpotential of diclofenac electrooxidation. ► The modified electrode has good stability and reproducibility.

  6. MWCNTs/Cu(OH){sub 2} nanoparticles/IL nanocomposite modified glassy carbon electrode as a voltammetric sensor for determination of the non-steroidal anti-inflammatory drug diclofenac

    Energy Technology Data Exchange (ETDEWEB)

    Arvand, Majid, E-mail: arvand@guilan.ac.ir; Gholizadeh, Tahereh M.; Zanjanchi, Mohammad Ali

    2012-08-01

    This paper describes the development and utilization of a new nanocomposite consisting of Cu(OH){sub 2} nanoparticles, hydrophobic ionic liquid 1-ethyl-3-methylimidazolium hexafluorophosphate (EMIMPF{sub 6}) and multiwalled carbon nanotubes for glassy carbon electrode modification. The nanocomposite was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM) along with energy-dispersive X-ray spectroscopy (EDX). The modified electrode was used for electrochemical characterization of diclofenac. Using differential pulse voltammetry, the prepared sensor showed good sensitivity and selectivity with low overpotential for the determination of diclofenac in the range from 0.18 to 119 {mu}M, with a detection limit of 0.04 {mu}M. Electrochemical studies suggested that the MWCNTs/Cu(OH){sub 2} nanoparticles/IL nanocomposite modified electrode provided a synergistic augmentation on the voltammetric behavior of electrochemical oxidation of diclofenac, which was indicated by the improvement of anodic peak current. Highlights: Black-Right-Pointing-Pointer This work examines oxidation of diclofenac at a nanocomposite modified electrode. Black-Right-Pointing-Pointer The salient feature of this electrode is large diffusion coefficient. Black-Right-Pointing-Pointer The proposed electrode decreased overpotential of diclofenac electrooxidation. Black-Right-Pointing-Pointer The modified electrode has good stability and reproducibility.

  7. Randomised controlled trial of tumour necrosis factor inhibitors against combination intensive therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews.

    Science.gov (United States)

    Scott, David L; Ibrahim, Fowzia; Farewell, Vern; O'Keeffe, Aidan G; Ma, Margaret; Walker, David; Heslin, Margaret; Patel, Anita; Kingsley, Gabrielle

    2014-10-01

    Rheumatoid arthritis (RA) is initially treated with methotrexate and other disease-modifying antirheumatic drugs (DMARDs). Active RA patients who fail such treatments can receive tumour necrosis factor inhibitors (TNFis), which are effective but expensive. We assessed whether or not combination DMARDs (cDMARDs) give equivalent clinical benefits at lower costs in RA patients eligible for TNFis. An open-label, 12-month, pragmatic, randomised, multicentre, two-arm trial [Tumour necrosis factor inhibitors Against Combination Intensive Therapy (TACIT)] compared these treatment strategies. We then systematically reviewed all comparable published trials. The TACIT trial involved 24 English rheumatology clinics. Active RA patients eligible for TNFis. The TACIT trial compared cDMARDs with TNFis plus methotrexate or another DMARD; 6-month non-responders received (a) TNFis if in the cDMARD group; and (b) a second TNFi if in the TNFi group. The Heath Assessment Questionnaire (HAQ) was the primary outcome measure. The European Quality of Life-5 Dimensions (EQ-5D), joint damage, Disease Activity Score for 28 Joints (DAS28), withdrawals and adverse effects were secondary outcome measures. Economic evaluation linked costs, HAQ changes and quality-adjusted life-years (QALYs). In total, 432 patients were screened; 104 started on cDMARDs and 101 started on TNFis. The initial demographic and disease assessments were similar between the groups. In total, 16 patients were lost to follow-up (nine in the cDMARD group, seven in the TNFi group) and 42 discontinued their intervention but were followed up (23 in the cDMARD group and 19 in the TNFi group). Intention-to-treat analysis with multiple imputation methods used for missing data showed greater 12-month HAQ score reductions with initial cDMARDs than with initial TNFis [adjusted linear regression coefficient 0.15, 95% confidence interval (CI) -0.003 to 0.31; p = 0.046]. Increases in 12-month EQ-5D scores were greater with initial c

  8. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What ... Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the principal biomedical and behavioral research agency ...

  9. 21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

    Science.gov (United States)

    2010-04-01

    ... adhesive. 872.3480 Section 872.3480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

  10. Allosteric regulation of epigenetic modifying enzymes.

    Science.gov (United States)

    Zucconi, Beth E; Cole, Philip A

    2017-08-01

    Epigenetic enzymes including histone modifying enzymes are key regulators of gene expression in normal and disease processes. Many drug development strategies to target histone modifying enzymes have focused on ligands that bind to enzyme active sites, but allosteric pockets offer potentially attractive opportunities for therapeutic development. Recent biochemical studies have revealed roles for small molecule and peptide ligands binding outside of the active sites in modulating the catalytic activities of histone modifying enzymes. Here we highlight several examples of allosteric regulation of epigenetic enzymes and discuss the biological significance of these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Drug Facts

    Medline Plus

    Full Text Available ... Where Can Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking ... You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English ...

  12. Hazardous Drugs

    Science.gov (United States)

    ... and hazardous drugs in the workplace. Pharmacy . OSHA Hospital eTool. Reviews safety and health topics related to hazardous drugs including drug handling, administration, storage, and disposal. OSHA has identified worker exposure ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment ...

  14. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  16. Club Drugs

    Science.gov (United States)

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... regarding prevention and treatment of MDMA. ( September 2017 ) View all related publications Related NIDA Notes Articles Narrative ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  18. Drug Facts

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    Full Text Available ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ...

  19. Drug Facts

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    Full Text Available ... Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her ...

  20. Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA).

    Science.gov (United States)

    Singh, Jasvinder A; Hossain, Alomgir; Tanjong Ghogomu, Elizabeth; Mudano, Amy S; Tugwell, Peter; Wells, George A

    2016-11-17

    We performed a systematic review, a standard meta-analysis and network meta-analysis (NMA), which updates the 2009 Cochrane Overview, 'Biologics for rheumatoid arthritis (RA)'. This review is focused on biologic monotherapy in people with RA in whom treatment with traditional disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) had failed (MTX/other DMARD-experienced). To assess the benefits and harms of biologic monotherapy (includes anti-tumor necrosis factor (TNF) (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) or non-TNF (abatacept, anakinra, rituximab, tocilizumab)) or tofacitinib monotherapy (oral small molecule) versus comparator (placebo or MTX/other DMARDs) in adults with RA who were MTX/other DMARD-experienced. We searched for randomized controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2015, Issue 6, June), MEDLINE (via OVID 1946 to June 2015), and Embase (via OVID 1947 to June 2015). Article selection, data extraction and risk of bias and GRADE assessments were done in duplicate. We calculated direct estimates with 95% confidence intervals (CI) using standard meta-analysis. We used a Bayesian mixed treatment comparisons (MTC) approach for NMA estimates with 95% credible intervals (CrI). We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We calculated absolute measures as risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB). This update includes 40 new RCTs for a total of 46 RCTs, of which 41 studies with 14,049 participants provided data. The comparator was placebo in 16 RCTs (4,532 patients), MTX or other DMARD in 13 RCTs (5,602 patients), and another biologic in 12 RCTs (3,915 patients). Monotherapy versus placeboBased on moderate-quality direct evidence, biologic monotherapy (without concurrent MTX/other DMARDs) was associated with a clinically meaningful and statistically significant

  1. A Modified P1 Moiety Enhances in vitro Antiviral Activity against Various Multi-Drug-Resistant HIV-1 Variants and in vitro CNS Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Masayuki; Salcedo-Gómez, Pedro Miguel; Zhao, Rui; Yedidi, Ravikiran S.; Das, Debananda; Bulut, Haydar; Delino, Nicole S.; Sheri, Venkata Reddy; Ghosh, Arun K.; Mitsuya, Hiroaki (Kumamoto); (NIH); (Purdue)

    2016-09-12

    We here report that GRL-10413, a novel non-peptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (EC50: 0.00035 - 0.0018 μM) with minimal cytotoxicity (CC50: 35.7 μM). GRL-10413 blocked the infectivity and replication of HIV-1NL4-3variants selected by up to 5 μM concentrations of atazanavir, lopinavir, or amprenavir (EC50: 0.0021 - 0.0023 μM). GRL-10413 also maintained its strong antiviral activity against multi-drug-resistant clinical HIV-1 variants isolated from patients, who no longer responded to various antiviral regimens after long-term antiretroviral therapy. The development of resistance against GRL-10413 was significantly delayed compared to that of APV. In addition, GRL-10413 showed a favorable central nervous system (CNS) penetration property as assessed with anin vitroblood brain barrier (BBB) reconstruction system. Analysis of the crystal structure of HIV-1 protease in complex with GRL-10413 demonstrated that the modified P1 moiety of GRL-10413 has a greater hydrophobic surface area and makes greater van der Waals contacts with active-site amino acids of protease than in the case of darunavir. Moreover, the chlorine substituent in the P1 moiety interacts with protease in two distinct configurations. The present data demonstrate that GRL-10413 has desirable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants with favorable CNS-penetration capability and that the newly modified P1-moiety may confer desirable features in designing novel anti-HIV-1 PIs.

  2. Validated modified Lycopodium spore method development for ...

    African Journals Online (AJOL)

    Validated modified lycopodium spore method has been developed for simple and rapid quantification of herbal powdered drugs. Lycopodium spore method was performed on ingredients of Shatavaryadi churna, an ayurvedic formulation used as immunomodulator, galactagogue, aphrodisiac and rejuvenator. Estimation of ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath ... Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  5. Drug Facts

    Medline Plus

    Full Text Available ... Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Information about this page Click on the button that says "Listen" on any page and the computer will read the text to you. This website talks ...

  6. Identifying Drugs

    Science.gov (United States)

    ... and Affect Teens The Negative Health Effects of Marijuana Use State and Federal Drug Laws Treatment and Recovery Federal Student Aid and Consequences of a Drug Conviction School Failure VIDEO: Taking Prescription Drugs to Get High—A Bad Idea Drugged Driving—What You Should Know How ...

  7. Development of a modified electrode with amine-functionalized TiO{sub 2}/multi-walled carbon nanotubes nanocomposite for electrochemical sensing of the atypical neuroleptic drug olanzapine

    Energy Technology Data Exchange (ETDEWEB)

    Arvand, Majid, E-mail: arvand@guilan.ac.ir; Palizkar, Bahareh

    2013-12-01

    In this work, using of amine-functionalized TiO{sub 2}/multi-walled carbon nanotubes (NH{sub 2}-TiO{sub 2}-MWCNTs) nanocomposite for modification of glassy carbon electrode (GCE) was investigated. The nanocomposite was characterized by Fourier transformed infrared spectroscopy, transmission electron microscopy and scanning electron microscopy. The efficiency of modified electrode for electrocatalytic the oxidation of olanzapine was studied by cyclic voltammetry, square wave voltammetry and chronoamperometry. The electrochemical measurements were carried out in phosphate-buffered solution (PBS, pH 5.0). The NH{sub 2}-TiO{sub 2}-MWCNTs/GCE provided high surface area and more sensitive performance. The charge transfer coefficient (α) and the apparent charge transfer rate constant (k{sub s}) were calculated to be equal to 0.42 and 0.173 s{sup −1}, respectively. The square wave voltammetry exhibited two linear dynamic ranges and a detection limit of 0.09 μM of olanzapine. In addition, the modified electrode was employed for the determination of olanzapine in pharmaceutical and human blood serum samples in order to illustrate the applicability of proposed method. - Highlights: • A simple and rapid sensor for determination of olanzapine in tablet and serum was prepared. • The amine-functionalized TiO{sub 2}-MWCNTs/GCE showed an obvious increase in surface area. • The presence of NH{sub 2}-TiO{sub 2} nanoparticles showed good ability to distinguish the response of olanzapine.

  8. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  9. Evaluation of Modified Risk Claim Advertising Formats for Camel Snus

    Science.gov (United States)

    Fix, Brian V.; Adkison, Sarah E.; O'Connor, Richard J.; Bansal-Travers, Maansi; Cummings, K. Michael; Rees, Vaughan W.; Hatsukami, Dorothy K.

    2017-01-01

    Objectives: The US Food and Drug Administration (FDA) has regulatory authority for modified risk tobacco product advertising claims. To guide future regulatory efforts, we investigated how variations in modified risk claim advertisements influence consumer perceptions of product risk claims for Camel Snus. Methods: Young people and adults (15-65),…

  10. The effects of anti-DNA topoisomerase II drugs, etoposide and ellipticine, are modified in root meristem cells of Allium cepa by MG132, an inhibitor of 26S proteasomes.

    Science.gov (United States)

    Żabka, Aneta; Winnicki, Konrad; Polit, Justyna Teresa; Maszewski, Janusz

    2015-11-01

    DNA topoisomerase II (Topo II), a highly specialized nuclear enzyme, resolves various entanglement problems concerning DNA that arise during chromatin remodeling, transcription, S-phase replication, meiotic recombination, chromosome condensation and segregation during mitosis. The genotoxic effects of two Topo II inhibitors known as potent anti-cancer drugs, etoposide (ETO) and ellipticine (EPC), were assayed in root apical meristem cells of Allium cepa. Despite various types of molecular interactions between these drugs and DNA-Topo II complexes at the chromatin level, which have a profound negative impact on the genome integrity (production of double-strand breaks, chromosomal bridges and constrictions, lagging fragments of chromosomes and their uneven segregation to daughter cell nuclei), most of the elicited changes were apparently similar, regarding both their intensity and time characteristics. No essential changes between ETO- and EPC-treated onion roots were noticed in the frequency of G1-, S-, G2-and M-phase cells, nuclear morphology, chromosome structures, tubulin-microtubule systems, extended distribution of mitosis-specific phosphorylation sites of histone H3, and the induction of apoptosis-like programmed cell death (AL-PCD). However, the important difference between the effects induced by the ETO and EPC concerns their catalytic activities in the presence of MG132 (proteasome inhibitor engaged in Topo II-mediated formation of cleavage complexes) and relates to the time-variable changes in chromosomal aberrations and AL-PCD rates. This result implies that proteasome-dependent mechanisms may contribute to the course of physiological effects generated by DNA lesions under conditions that affect the ability of plant cells to resolve topological problems that associated with the nuclear metabolic activities. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs

    NARCIS (Netherlands)

    de Vries, Max; Seppala, Lotta J.; Daams, Joost G.; van de Glind, Esther M. M.; Masud, Tahir; van der Velde, Nathalie

    2018-01-01

    Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is

  12. Drug Facts

    Medline Plus

    Full Text Available ... Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with ... problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ...

  14. Drug Abuse

    Science.gov (United States)

    ... and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes ... Options? What Is Recovery? What Is a Relapse? How Can Friends and Family Help? Where Can Someone ...

  18. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Drug metabolism may be defined as the biochemical modifica- tion of one chemical form to another, occurring usually through ..... Endogenous. Enzyme. Drugs. Cofactor. Glucuronidation. UDP glucoronic. UDP-. Chloramphenicol, acid glucuronosyltransferase morphine, paracetamol, salicylic acid, fenoprofen, desipramine,.

  19. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  1. Study Drugs

    Science.gov (United States)

    ... What Are Study Drugs? Doctors prescribe medicines like Adderall and Ritalin to treat conditions like attention deficit ... stimulants are used as study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  5. On Modified Bar recursion

    DEFF Research Database (Denmark)

    Oliva, Paulo Borges

    2002-01-01

    Modified bar recursion is a variant of Spector's bar recursion which can be used to give a realizability interpretation of the classical axiom of dependent choice. This realizability allows for the extraction of witnesses from proofs of forall-exists-formulas in classical analysis. In this talk I...... shall report on results regarding the relationship between modified and Spector's bar recursion. I shall also show that a seemingly weak form of modified bar recursion is as strong as "full" modified bar recursion in higher types....

  6. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs ... adicción. English Español About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  12. Drug Resistance

    Science.gov (United States)

    ... infected with a drug-resistant strain of HIV. Drug-resistance testing results are used to decide which HIV medicines to include in a person’s first HIV regimen. After treatment is started, drug-resistance testing is repeated if ...

  13. Drug: D07478 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07478 Drug Aurotioprol; Allochrysine (TN) ... C3H6AuO4S2.Na ... Anti-inflammatory ... DG01912 ... Gold... preparations ... DG01985 ... Disease modifying anti-rheumatic drugs (DMARDs) ... DG01912 ... Gold preparat...ions ATC code: M01CB05 ... Gold preparation ... CAS: 27279-43-2 PubChem: 96024436 NIKKAJI: J35.087G ...

  14. Drug: D08521 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08521 Drug Sodium aurothiosulfate (INN); Gold sodium thiosulfate, dihydrate; Cryt...ioro (TN) ... AuS4O6. 3Na. 2H2O D08521.gif ... Anti-inflammatory ... DG01912 ... Gold preparations ... DG01985 ... Disease m...odifying anti-rheumatic drugs (DMARDs) ... DG01912 ... Gold preparations ATC code: M01CB02 ... Gold preparation ... CAS: 10210-36-3 PubChem: 96025206 ChEMBL: CHEMBL3833379 ...

  15. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  16. Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

    Science.gov (United States)

    Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

    2017-09-01

    To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

  17. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

    Apr 12, 2009 ... tion of drugs, especially hemp (Cannabis. Sativa), became entrenched. Oloruntoba. (2006) explained that the vigour and sus- tained efforts to legislate against drugs in contemporary Nigeria was because of the growing notoriety of the country as a transit point or centre for recruitment of drug couriers, and a ...

  18. Magnetic hyperthermia and pH-responsive effective drug delivery to the sub-cellular level of human breast cancer cells by modified CoFe2O4nanoparticles.

    Science.gov (United States)

    Oh, Yunok; Moorthy, Madhappan Santha; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Oh, Junghwan

    2017-02-01

    Magnetic iron oxide nanoparticles (MNPs) have been extensively utilized in a wide range of biomedical applications including magnetic hyperthermia agent. To improve the efficiency of the MNPs in therapeutic applications, in this study, we have synthesized CoFe 2 O 4 nanoparticles and its surface was further functionalized with meso-2,3-dimercaptosuccinic acid (DMSA). The anticancer agent, Doxorubucin (DOX) was conjugated with CoFe 2 O 4 @DMSA nanoparticle to evaluate the combined effects of thermotherapy and chemotherapy. The drug delivery efficiency of the DOX loaded CoFe 2 O 4 @DMSA nanoparticles were examined based on magnetically triggered delivery of DOX into the subcellular level of cancer cells by using MDA-MB-231 cell line. The amine part of the DOX molecules were effectively attached through an electrostatic interactions and/or hydrogen bonding interactions with the carboxylic acid groups of the DMSA functionalities present onto the surface of the CoFe 2 O 4 nanoparticles. The DOX loaded CoFe 2 O 4 @DMSA nanoparticles can effectively uptake with cancer cells via typical endocytosis process. After endocytosis, DOX release from CoFe 2 O 4 nanoparticles was triggered by intracellular endosomal/lysosomal acidic environments and the localized heat can be generated under an alternating magnetic field (AMF). In the presence of AMF, the released DOX molecules were accumulated with high concentrations into the subcellular level at a desired sites and exhibited a synergistic effect of an enhanced cell cytotoxicity by the combined effects of thermal-chemotherapy. Importantly, pH- and thermal-responsive Dox-loaded CoFe 2 O 4 nanoparticles induced significant cellular apoptosis more efficiently mediated by active mitochondrial membrane and ROS generation than the free Dox. Thus, the Dox-loaded CoFe 2 O 4 @DMSA nanoparticles can be used as a potential therapeutic agent in cancer therapy by combining the thermo-chemotherapy techniques. Copyright © 2016. Published by

  19. [NEPHROTOXIC DRUGS].

    Science.gov (United States)

    Popović, B; Šutić, I; Marković, N Bašić

    2016-12-01

    Renal tissue is sensitive to the effect of potentially nephrotoxic drugs and other substances that are available over-the-counter or can be purchased at healthy food stores or elsewhere, and harmful substances from the environment. The harmful effects of these substances lead to the development of recognizable clinical syndromes, including acute or chronic renal failure, tubulopathy, and proteinuria. Risk factors that influence the development of kidney disease induced by drugs are divided into those related to patient characteristics, drug characteristics, and renal function. Drugs that commonly exhibit nephrotoxic effects are analgesics, antimicrobials, chemotherapeutics, contrast agents, immunosuppressants, herbal preparations and substances containing heavy metals. Family physician must carefully observe their patients, nurturing individual approach to drug selection and determining the dose. Renal function can quickly return to normal if the damage is recognized on time. Recent research yields insights into the identification of new biomarkers that will contribute to early detection of drug induced kidney damage.

  20. Phosphine modified cobalt hydroformylation

    Energy Technology Data Exchange (ETDEWEB)

    Rensburg, H. van; Tooze, R.P.; Foster, D.F. [Sasol Technology UK, St. Andrews (United Kingdom); Janse van Rensburg, W. [Sasol Technology, Sasolburg (South Africa)

    2006-07-01

    An ongoing challenge in phosphine modified cobalt hydroformylation is the fundamental understanding of the electronic and steric properties of phosphine ligands that influence the selectivity and activity of the catalytic reaction. A series of acyclic and cyclic phosphines have been prepared and tested in phosphine modified cobalt hydroformylation of 1-octene. Molecular modelling on a series of phospholanes showed some interesting theoretical and experimental correlations. We also evaluated the use of N-heterocyclic carbenes as an alternative for phosphines in modified cobalt hydroformylation. (orig.)

  1. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  2. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  3. Genetic modifiers of Huntington's disease.

    Science.gov (United States)

    Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

    2014-09-15

    Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs. © 2014 International Parkinson and Movement Disorder Society.

  4. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  5. Modified Nance palatal button

    Directory of Open Access Journals (Sweden)

    Nitin Arora

    2015-01-01

    Full Text Available This paper describes modified Nance palatal button by which problems encountered in the palatal region around the acrylic button during space closure and molar distalization can be minimized.

  6. Lipid-modifying therapy

    African Journals Online (AJOL)

    2009-03-20

    Mar 20, 2009 ... reduction, the cost of the drug, the potential for interactions with other drugs the patient is taking and its ability to reduce cardiovascular events. Statins are well tolerated by most patients and have an excellent safety record. The two major side-effects are hepatotoxicity with transient increases in liver ...

  7. Biological response modifiers

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    Much of what used to be called immunotherapy is now included in the term biological response modifiers. Biological response modifiers (BRMs) are defined as those agents or approaches that modify the relationship between the tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic effects.'' Most of the early work with BRMs centered around observations of spontaneous tumor regression and the association of tumor regression with concurrent bacterial infections. The BRM can modify the host response in the following ways: Increase the host's antitumor responses through augmentation and/or restoration of effector mechanisms or mediators of the host's defense or decrease the deleterious component by the host's reaction; Increase the host's defenses by the administration of natural biologics (or the synthetic derivatives thereof) as effectors or mediators of an antitumor response; Augment the host's response to modified tumor cells or vaccines, which might stimulate a greater response by the host or increase tumor-cell sensitivity to an existing response; Decrease the transformation and/or increase differentiation (maturation) of tumor cells; or Increase the ability of the host to tolerate damage by cytotoxic modalities of cancer treatment.

  8. Drug Facts

    Medline Plus

    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  9. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  10. Drug Facts

    Medline Plus

    Full Text Available ... Say if You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button that says "Listen" on any page and the computer will read the ... Videos Information About ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often ... NIH is a component of the U.S. Department of Health and Human Services . PDF documents require the free Adobe Reader . ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  13. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Chemistry of Drug Metabolism. Drug metabolism is a chemical process, where enzymes play a crucial role in the conversion of one chemical species to another. The major family of enzymes associated with these metabolic reactions is the cytochrome P450 family. The structural features and functional activity of these ...

  14. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  15. Capping Drugs

    Indian Academy of Sciences (India)

    In the process of treatment, drugs are also used for medical diagnosis and for ... ing cells. Since cancer cells grow at a faster rate than the normal .... ity characteristics. After intake, the N-methyl group is cleaved in the liver to release the physiologically active drug. Similarly, membrane transportation characteristics of the neu-.

  16. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  17. Polymeric materials and formulation technologies for modified-release tablet development.

    Science.gov (United States)

    Zarate, J; Igartua, M; Hernández, R M; Pedraz, J L

    2009-11-01

    Over the last years significant advances have been made in the area of drug delivery with the development of modified-release (MR) dosage forms. The present review is divided into two parts, one dealing with technologies for the design of modified-release drug delivery tablets and the other with the use of synthetic and natural polymers that are capable of controlling drug release.

  18. [National consensus on the modified Atkins diet].

    Science.gov (United States)

    Vaccarezza, María; Agustinho, Ariela; Alberti, M Julia; Argumedo, Laura; Armeno, Marisa; Blanco, Virginia; Bouquet, Cecilia; Cabrera, Analía; Caraballo, Roberto; Caramuta, Luciana; Cresta, Araceli; de Grandis, Elizabeth S; DeMartini, Martha G; Diez, Cecilia; Diz, Mariana; Dlugoszewski, Corina; Escobal, Nidia; Ferrero, Hilario; Galicchio, Santiago; Gambarini, Victoria; Gamboni, Beatriz; Gonzalez, Lara; Guisande, Silvina; Hassan, Amal; Matarrese, Pablo; Mestre, Graciela; Pesce, Laura; Rios, Viviana; Semprino, Marcos; Sosa, Patricia; Toma, Marisol; Viollaz, Rocío; Panico, Luis

    2016-04-16

    Epilepsy is a chronic disease that affects 0.5-1% of the population. One third of the patients become refractory to antiepileptic drugs. Among the non-pharmacological treatments available, the modified Atkins diet is an effective treatment used since 2003 as another alternative for children and adults with refractory epilepsy. The Ketogenic Diet National Committee, which depends on the Argentine Society of Pediatric Neurology, elaborated this consensus on the modified Atkins diet, basing itself on a review of the literature and on their clinical experience. This consensus in Spanish explains the different aspects to be taken into account regarding the modified Atkins diet, patient selection, implementation, different controls and adverse effects. Unlike the classic ketogenic diet, the modified Atkins diet is initiated without fasting or hospital stay, nor does it require protein, calorie or fluid restriction, thus improving patient palatability and consequently patient tolerability. The modified Atkins diet is a useful treatment for patients with intractable epilepsy. The publication of this consensus offers the possibility for new centers to get oriented regarding this diet implementation.

  19. Modified nasolacrimal duct stenting

    International Nuclear Information System (INIS)

    Tian Min; Jin Mei; Chen Huanjun; Li Yi

    2008-01-01

    Objective: Traditional nasolacrimal duct stenting possesses some shortcoming including difficulty of pulling ball head guide wire from the nasal cavity with turbinate hypertrophy and nasal septal deviation. The new method of nose-oral tube track establishment can overcome the forementioned and increase the successful rate. Methods: 5 F catheter and arterial sheath were modified to be nasolacrimal duct stent delivery device respectively. Antegrade dacryocystography was taken firstly to display the obstructed site and followed by the modified protocol of inserting the guide wire through nasolacrimal duct and nasal cavity, and establishing the stent delivery track for retrograde stent placement. Results: 5 epiphora patients with failure implantation by traditional method were all succeeded through the modified stenting (100%). During 6-mouth follow-up, no serious complications and reocclusion occurred. Conclusion: The establishment of eye-nose-mouth-nose of external nasal guide wire track can improve the successful rate of nasolacrimal duct stenting. (authors)

  20. Skewon modified electrodynamics

    Science.gov (United States)

    Itin, Yakov

    2017-05-01

    Premetric electrodynamics is a representation of classical electrodynamics based on topological conservation laws. This model predicts a covariant extension of classical theory by dilaton, axion, and skewon as copartners of photon. In this paper, we report on some recent results on skewon modification of classical electrodynamics. We present the skewon modified dispersion relation for electromagnetic wave propagation. It yields several kinds of the birefringence effect of topologically different types. The superluminal character of wave propagation and the Higgs-type effect for the symmetric skewon are indicated. We present the skewon modified photon propagator and discuss the corresponding modification of Coulomb’s law.

  1. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...... Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process...

  2. Drug Facts

    Science.gov (United States)

    ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  3. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  5. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain ... About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... changes in her life. She finds support from family and friends who don't use marijuana. Haga ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ... marijuana, "Cristina" is making positive changes in her life. She finds support from family and friends who ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and ... Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  14. EAMJ Modifiable 10.indd

    African Journals Online (AJOL)

    2010-02-02

    Feb 2, 2010 ... MODIFIABLE FACTORS ASSOCIATED WITH ACTIVE PULMONARY TUBERCULOSIS IN A KENYAN PRISON. A. S. Amwayi, MBChB, MSc., ... University of Agriculture and Technology, P.O. Box 62000- 0200, Nairobi, Kenya and E. M. Muchiri, MSc, PhD., Division ..... Diabetes and low BMI. 223452.81.

  15. An overview of the biological disease modifying drugs available for ...

    African Journals Online (AJOL)

    In addition, the combined use of TNF-α inhibitors and methotrexate prevents the formation of antibodies to the TNF-α inhibitors. The available TNF-α inhibitors bind to both soluble and membrane bound TNF-α.2,4. Adverse effects associated with TNF-α inhibitors are associated with the role of TNF-α in the immune system.

  16. An overview of the biological disease modifying drugs available for ...

    African Journals Online (AJOL)

    Tumour necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of rheumatoid disorders and is the target of four biological DMARDs, etanercept, infliximab, golimumab and adalimumab. The other biological DMARDs include abatacept, rituximab and tocilizumab and these prevent T-cell costimulation, ...

  17. Food, physiology and drug delivery.

    Science.gov (United States)

    Varum, F J O; Hatton, G B; Basit, A W

    2013-12-05

    Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  19. [Drug promiscuity].

    Science.gov (United States)

    Guo, Zong-ru

    2011-04-01

    It is essential for a successful drug to possess two basic characteristics: satisfactory pharmacological action with sufficient potency and selectivity; good druggability with eligible physicochemical, pharmacokinetic and safety profiles, as well as structural novelty. Promiscuity is defined as the property of a drug to act with multiple molecular targets and exhibit distinct pharmacological effects. Promiscuous drugs are the basis of polypharmacology and the causes for side effects and unsuitable DMPK. Drug promiscuity originates from protein promiscuity. In order to accommodate, metabolize and excrete various endo- and exogenous substances, protein acquired the capability during evolution to adapt a wide range of structural diversity, and it is unnecessary to reserve a specific protein for every single ligand. The structures of target proteins are integration of conservativity and diversity. The former is represented by the relatively conservative domains for secondary structures folding, which leads to overlapping in ligand-binding and consequent cross-reactivity of ligands. Diversity, however, embodies the subtle difference in structures. Similar structural domain may demonstrate different functions due to alteration of amino acid sequences. The phenomenon of promiscuity may facilitate the "design in" of multi-target ligands for the treatment of complicated diseases, whereas it should be appropriately handled to improve druggability. Therefore, one of the primary goals in drug design is to scrutinize and manipulate the "merits and faults" of promiscuity. This review discusses the application of promiscuity in drug design for receptors, enzymes, ion channels and cytochrome P450. It also briefly describes the methods to predict ligand promiscuity based on either target or ligand structures.

  20. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  1. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  2. Tip-modified Propellers

    DEFF Research Database (Denmark)

    Andersen, Poul

    1999-01-01

    The paper deals with tip-modified propellers and the methods which, over a period of two decades, have been applied to develop such propellers. The development is driven by the urge to increase the efficiency of propellers and can be seen as analogous to fitting end plates and winglets to aircraft...... propeller, have efficiency increases of a reasonable magnitude in both open-water and behind-ship conditions....

  3. Genetically Modified Organisms

    Directory of Open Access Journals (Sweden)

    Claro Llaguno

    2001-06-01

    Full Text Available Recent reports have brought to public attention concerns about Bt corn and genetically modified organisms (GMO in general. The timing, it seems, is most appropriate considering two related developments early this year: the final approval of the Cartagena Protocol on Biosafety in Montreal on January 29, 2001, and the OECD Edinburgh Conference on GM food safety last February 28- March 1, 2001. The protocol makes clear that GMOs include all living modified organisms (LMO defined as "any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology". This includes seeds, live fish, and other organisms intentionally obtained for release to the environment. It would seem that the common understanding about GMOs as referring to farm-to-table products is perforce expanded to embrace genetically modified farm animals and aquatic resources. Being a trade agreement, the Montreal accord primarily deals with the safety issues related to the transboundary movement of LMOs around the globe. The OECD conference on the other hand, called for an international body "to address all sides of the GM debate" in response to the public outcry, particularly in Western Europe, regarding the risks the new products pose to human health and the environment. Some points of contention, which remain unresolved, include issues such as whether countries should be allowed to develop their own GM food based on their needs, and whether a global moratorium on GMOs and mandatory labeling should be enforced worldwide.

  4. Acid-degradable and bioerodible modified polyhydroxylated materials

    Science.gov (United States)

    Frechet, Jean M. J.; Bachelder, Eric M.; Beaudette, Tristan T.; Broaders, Kyle E.

    2017-05-09

    Compositions and methods of making a modified polyhydroxylated polymer comprising a polyhydroxylated polymer having reversibly modified hydroxyl groups, whereby the hydroxyl groups are modified by an acid-catalyzed reaction between a polydroxylated polymer and a reagent such as acetals, aldehydes, vinyl ethers and ketones such that the modified polyhydroxylated polymers become insoluble in water but freely soluble in common organic solvents allowing for the facile preparation of acid-sensitive materials. Materials made from these polymers can be made to degrade in a pH-dependent manner. Both hydrophobic and hydrophilic cargoes were successfully loaded into particles made from the present polymers using single and double emulsion techniques, respectively. Due to its ease of preparation, processability, pH-sensitivity, and biocompatibility, of the present modified polyhydroxylated polymers should find use in numerous drug delivery applications.

  5. Drug Allergy

    African Journals Online (AJOL)

    EL-HAKIM

    Rasha H. El-Owaidy. Immunology Unit, Department of Pediatrics, Ain Shams University, Cairo. Introduction. Adverse reactions to pharmaceutical and diagnostic products constitute a major hazard in the practice of medicine and are responsible for substantial morbidity and cost. Adverse drug reactions can be divided into ...

  6. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  7. Capping Drugs

    Indian Academy of Sciences (India)

    It is well documented that till recent times drugs derived from plants were used to relieve patients from suffering. But at the turn of the last century, with the improvement in purification meth- ods using chromatographic techniques, single compounds with well-defined structure became available for testing and treat- ment.

  8. Drugs reviews

    African Journals Online (AJOL)

    Angel_D

    chlorpropamide] and biguanides [e.g. metformin]), steroids and dapsone. The effectiveness of these drugs is likely to be reduced. Side-effects are uncommon but include: ▫ Skin reactions: rash, urticaria, flushing. Fortunately many of these reactions are self-limiting and gradually clear; the patient only needs symptomatic ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  10. Misused Drug

    African Journals Online (AJOL)

    analgesic effects by antagonising a subset of glutamate receptors ... unpleasant dreams up to 24hrs after the drug has been given.7 ... are intact. The amnesic effect of ketamine, which often persists for up to one hour after recovery of consciousness, cnsuree that there is no recall of surgery or anaesthesia. Effects on the War ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  12. Drugged Driving

    Science.gov (United States)

    ... Pain Prevention Recovery Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications ... mind-altering ingredient, in the blood. But the role that marijuana plays in crashes is ... age, gender, race, and presence of alcohol. 9 More research ...

  13. Prescription Drugs

    Science.gov (United States)

    ... Future survey shows long term decline in illicit drug use, prescription opioid abuse, cigarette and alcohol use among the nation’s youth. View Online Download PDF Monitoring the Future 2013 Survey Results: College and Adults Published: April 30, 2015 In 2013, ...

  14. Real-life experience of using conventional disease-modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA). Retrospective analysis of the efficacy of methotrexate, sulfasalazine, and leflunomide in PsA in comparison to spondyloarthritides other than PsA and literature review of the use of conventional DMARDs in PsA.

    Science.gov (United States)

    Roussou, Euthalia; Bouraoui, Aicha

    2017-03-01

    With the aim of assessing the response to treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) used in patients with psoriatic arthritis (PsA), data on methotrexate, sulfasalazine (SSZ), and leflunomide were analyzed from baseline and subsequent follow-up (FU) questionnaires completed by patients with either PsA or other spondyloarthritides (SpAs). A single-center real-life retrospective analysis was performed by obtaining clinical data via questionnaires administered before and after treatment. The indices used were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), wellbeing (WB), and treatment effect (TxE). The indices measured at baseline were compared with those measured on one occasion in a FU visit at least 1 year later. A total of 73 patients, 51 with PsA (mean age 49.8±12.8 years; male-to-female ratio [M:F]=18:33) and 22 with other SpAs (mean age 50.6±16 years; M:F=2:20), were studied. BASDAI, BASFI, and WB displayed consistent improvements during FU assessments in both PsA patients and controls in comparison to baseline values. SSZ exhibited better efficacy as confirmed by TxE in both PsA patients and controls. ESR and CRP displayed no differences in either the PsA or the SpA group between the cases before and after treatment. Real-life retrospective analysis of three DMARDs used in PsA (and SpAs other than PsA) demonstrated that all three DMARDs that were used brought about improvements in BASDAI, BASFI, TxE, and WB. However, the greatest improvements at FU were seen with SSZ use in both PsA and control cohorts.

  15. Drug abuse first aid

    Science.gov (United States)

    ... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

  16. Modified harmony search

    Science.gov (United States)

    Mohamed, Najihah; Lutfi Amri Ramli, Ahmad; Majid, Ahmad Abd; Piah, Abd Rahni Mt

    2017-09-01

    A metaheuristic algorithm, called Harmony Search is quite highly applied in optimizing parameters in many areas. HS is a derivative-free real parameter optimization algorithm, and draws an inspiration from the musical improvisation process of searching for a perfect state of harmony. Propose in this paper Modified Harmony Search for solving optimization problems, which employs a concept from genetic algorithm method and particle swarm optimization for generating new solution vectors that enhances the performance of HS algorithm. The performances of MHS and HS are investigated on ten benchmark optimization problems in order to make a comparison to reflect the efficiency of the MHS in terms of final accuracy, convergence speed and robustness.

  17. Modified geometry three-layered tablet as a platform for class II ...

    African Journals Online (AJOL)

    Modified geometry three-layered tablet as a platform for class II drugs zero-order release system. Abdullah Monahi Albogami, Mustafa E. Omer, Abdulkareem M. Al Bekairy, Abdulmalik Alkatheri, Alaa Eldeen B. Yassin ...

  18. Modified Clipped LMS Algorithm

    Directory of Open Access Journals (Sweden)

    Lotfizad Mojtaba

    2005-01-01

    Full Text Available Abstract A new algorithm is proposed for updating the weights of an adaptive filter. The proposed algorithm is a modification of an existing method, namely, the clipped LMS, and uses a three-level quantization ( scheme that involves the threshold clipping of the input signals in the filter weight update formula. Mathematical analysis shows the convergence of the filter weights to the optimum Wiener filter weights. Also, it can be proved that the proposed modified clipped LMS (MCLMS algorithm has better tracking than the LMS algorithm. In addition, this algorithm has reduced computational complexity relative to the unmodified one. By using a suitable threshold, it is possible to increase the tracking capability of the MCLMS algorithm compared to the LMS algorithm, but this causes slower convergence. Computer simulations confirm the mathematical analysis presented.

  19. Biodegradable modified Phba systems

    International Nuclear Information System (INIS)

    Aniscenko, L.; Dzenis, M.; Erkske, D.; Tupureina, V.; Savenkova, L.; Muizniece - Braslava, S.

    2004-01-01

    Compositions as well as production technology of ecologically sound biodegradable multicomponent polymer systems were developed. Our objective was to design some bio plastic based composites with required mechanical properties and biodegradability intended for use as biodegradable packaging. Significant characteristics required for food packaging such as barrier properties (water and oxygen permeability) and influence of γ-radiation on the structure and changes of main characteristics of some modified PHB matrices was evaluated. It was found that barrier properties were plasticizers chemical nature and sterilization with γ-radiation dependent and were comparable with corresponding values of typical polymeric packaging films. Low γ-radiation levels (25 kGy) can be recommended as an effective sterilization method of PHB based packaging materials. Purposely designed bio plastic packaging may provide an alternative to traditional synthetic packaging materials without reducing the comfort of the end-user due to specific qualities of PHB - biodegradability, Biocompatibility and hydrophobic nature

  20. Modified custom tray.

    Science.gov (United States)

    Ortensi, L; Strocchi, M L

    2000-08-01

    The use of a custom tray is highly desirable for accurate impression making in situations with multiple abutments. This article describes a modified custom tray fabrication method using autopolymerizing acrylic resin. The custom tray is fabricated by intraoral relining with autopolymerizing resin that is polymerized extraorally. The final impression is obtained during the same session after tray polymerization at 100 degrees C for 5 minutes. Relined areas are refined by trimming excess resin with burs of a known diameter to create a 2-mm clearance for the elastomer. For areas with subgingival finish lines, only 0.5 mm of resin is removed to direct the elastomer into the gingival sulcus. The procedure is time-saving because it reduces the need for a retraction cord and minimizes inaccuracies that would necessitate another impression.

  1. Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion.

    Science.gov (United States)

    Palasuk, Jadesada; Windsor, L Jack; Platt, Jeffrey A; Lvov, Yuri; Geraldeli, Saulo; Bottino, Marco C

    2018-04-01

    This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration. Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated. Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity. The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity. Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.

  2. Urine drug screen

    Science.gov (United States)

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  3. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  4. Other Drugs of Abuse

    Science.gov (United States)

    ... People Abuse » Other Drugs of Abuse Other Drugs of Abuse Listen There are many other drugs of abuse, ... and Rehab Resources About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  5. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  6. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  7. Cyclodextrin-Modified inorganic materials for the construction of nanocarriers.

    Science.gov (United States)

    Cutrone, Giovanna; Casas-Solvas, Juan M; Vargas-Berenguel, Antonio

    2017-10-15

    Inorganic nanoparticles, such as gold, silver, quantum dots and magnetic nanoparticles, offer a promising way to develop multifunctional nanoparticles for biomedical applications. Such nanoparticles have the potential to combine in a single, stable construct various functionalities, simultaneously providing imaging abilities, thermal therapies and the ability to deliver drugs in a targeted fashion. An approach for providing drug loading abilities to these inorganic nanoparticles consists in the modification of their surface with a coating of cyclodextrins, and thereby endowing the nanoparticles with the potential of functioning as drug nanocarriers. This review presents the advances carried out in the preparation of cyclodextrin-contained gold, silver, quantum dot and magnetic nanoparticles as well as their applications as drug nanocarriers. The nanoparticle surface can be modified incorporating cyclodextrin moieties, (i) in situ during the synthesis of the nanoparticles, either using the cyclodextrin as reducing agent or as stabilizer; or (ii) in a post-synthetic stage. The cyclodextrin coating contributes to provide biocompatibility to the nanoparticles and to reduce their cytotoxicity. Cyclodextrin-modified nanoparticles display a multivalent presentation of quasi-hydrophobic cavities that enables, not only drug loading in a non-covalent manner, but also the non-covalent assembly of targeting motifs and optical probes. This paper also provides an overview of some of the reported applications including the in vitro studies and, to a lesser extent, in vivo studies on the drug-loaded nanoparticles behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Magnetic polymer nanospheres for anticancer drug targeting

    International Nuclear Information System (INIS)

    JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J; Muckova, M

    2010-01-01

    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  9. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids

    2002-01-01

    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  10. Assessment of Postoperative Analgesic Drug Efficacy

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Kloster; Gögenur, Ismail; Torup, Henrik

    2017-01-01

    , therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. METHODS: Data from a randomized, double......: Our analyses demonstrate that the applied statistical method may alter the statistical significance and estimates of effect size of analgesic outcome variables in postoperative pain trials. Our findings underline the importance of defining valid statistical methods for future analgesic drug trials. We...... drug efficacy....

  11. Understanding drugs and behaviour

    National Research Council Canada - National Science Library

    Parrott, Andrew

    2004-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix xi Part I Drugs and Their Actions . . . . . . . . . . . . . . . . . . . . . . 1 Psychoactive drugs: introduction and overview . . . . . . . . 2 The brain...

  12. Polymeric micelles for drug targeting.

    Science.gov (United States)

    Mahmud, Abdullah; Xiong, Xiao-Bing; Aliabadi, Hamidreza Montazeri; Lavasanifar, Afsaneh

    2007-11-01

    Polymeric micelles are nano-delivery systems formed through self-assembly of amphiphilic block copolymers in an aqueous environment. The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and finally a possibility for the chemical manipulation of the core/shell structure have made polymeric micelles one of the most promising carriers for drug targeting. To date, three generations of polymeric micellar delivery systems, i.e. polymeric micelles for passive, active and multifunctional drug targeting, have arisen from research efforts, with each subsequent generation displaying greater specificity for the diseased tissue and/or targeting efficiency. The present manuscript aims to review the research efforts made for the development of each generation and provide an assessment on the overall success of polymeric micellar delivery system in drug targeting. The emphasis is placed on the design and development of ligand modified, stimuli responsive and multifunctional polymeric micelles for drug targeting.

  13. Drug abuse

    International Nuclear Information System (INIS)

    Simon, T.R.; Seastrunk, J.W.; Malone, G.; Knesevich, M.A.; Hickey, D.C.

    1991-01-01

    This paper reports that this study used SPECT to examine patients who have abused drugs to determine whether SPECT could identify abnormalities and whether these findings have clinical importance. Fifteen patients with a history of substance abuse (eight with cocaine, six with amphetamine, and one with organic solvent) underwent SPECT performed with a triple-headed camera and Tc-99m HMPAO both early for blood flow and later for functional information. These images were then processed into a 3D videotaped display used in group therapy. All 15 patients had multiple areas of decreased tracer uptake peppered throughout the cortex but mainly affecting the parietal lobes, expect for the organic solvent abuser who had a large parietal defect. The videotapes were subjectively described by a therapist as an exceptional tool that countered patient denial of physical damage from substance abuse. Statistical studies of recidivism between groups is under way

  14. Design and Synthesis of Epigenetic Drugs

    DEFF Research Database (Denmark)

    Leurs, Ulrike

    2014-01-01

    of histone- and DNA-modifying enzymes can lead to the development of diseases such as cancer. The histone demethylases of the KDM4 family have been implicated in a wide range of diseases, and are hence important drug targets. KDM4s belong to the bigger family of 2-OG oxygenases, an enzyme class sharing high...

  15. Solid-Phase Synthesis of Modified Peptides as Putative Inhibitors of Histone Modifying Enzymes

    DEFF Research Database (Denmark)

    Cohrt, Anders Emil O'Hanlon

    The role of histone modifications in the tight regulation of gene expression is emerging as a new area within drug discovery. The misregulation of histone modification levels has been linked with several life-threatening diseases, including cancer and diabetes, and reverting these irregularities...... may improve the prognosis of patients suffering from these diseases. The development of methodologies to modify peptides for use as peptide-based inhibitors of histone modifying enzymes is presented. Several different approaches for both N and C-terminal modification have been developed. Two broadly......,2,3-triazoles were cleanly deprotected by treatment with TFA (CH2Cl2). Four different libraries of histone demethylase inhibitor candidates have been synthesised based on metal chelation, cofactor mimicking and radial stabilising inhibition strategies. The libraries have all been synthesised on solid...

  16. Drugs and the Brain.

    Science.gov (United States)

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  17. MODIFIED GYPSUM BINDER

    Directory of Open Access Journals (Sweden)

    KONDRATEVA N. V.

    2017-02-01

    Full Text Available Summary. Statement of the problem. A disadvantage of the gypsum binder is the limited water resistance of products that historically led to the use of gypsum products mostly for internal construction and finishing works. To regulate the process of hydration and structure formation of the use of chemical additives that are introduced with the mixing water or in the production of the binder. As a rule, substances that increase the solubility of the gypsum binder referred to as the hardening accelerator, and substances which retard the solubility of the inhibitors of hardening of the mixture. Most accelerators and retarders hardening affect adversely on the final strength of the mixture. More effective impact on gypsum binder additives have plasticizers. The purpose of the article. Getting gypsum binder modified with the aim of improving its water resistance and improvement of some technological factors (the time of hardening, water gypsum ratio, etc. would reduce its shortcomings and expand the scope of application of the binder. Conclusion. The result of the research reviewed changes in the basic properties of the gypsum binder with the introduction of additives, plasticizers, and selected the most effective supplements to significantly reduce water gypsum ratio, to improve strength properties and to obtain gypsum binder more dense structure.

  18. Distinguishing modified gravity models

    Energy Technology Data Exchange (ETDEWEB)

    Brax, Philippe [Institut de Physique Théorique, Université Paris-Saclay, CEA, CNRS, F-91191 Gif/Yvette Cedex (France); Davis, Anne-Christine, E-mail: philippe.brax@cea.fr, E-mail: A.C.Davis@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Cambridge, CB3 0WA (United Kingdom)

    2015-10-01

    Modified gravity models with screening in local environments appear in three different guises: chameleon, K-mouflage and Vainshtein mechanisms. We propose to look for differences between these classes of models by considering cosmological observations at low redshift. In particular, we analyse the redshift dependence of the fine structure constant and the proton to electron mass ratio in each of these scenarios. When the absorption lines belong to unscreened regions of space such as dwarf galaxies, a time variation would be present for chameleons. For both K-mouflage and Vainshtein mechanisms, the cosmological time variation of the scalar field is not suppressed in both unscreened and screened environments, therefore enhancing the variation of constants and their detection prospect. We also consider the time variation of the redshift of distant objects using their spectrocopic velocities. We find that models of the K-mouflage and Vainshtein types have very different spectroscopic velocities as a function of redshift and that their differences with the Λ-CDM template should be within reach of the future ELT-HIRES observations.

  19. Distinguishing modified gravity models

    International Nuclear Information System (INIS)

    Brax, Philippe; Davis, Anne-Christine

    2015-01-01

    Modified gravity models with screening in local environments appear in three different guises: chameleon, K-mouflage and Vainshtein mechanisms. We propose to look for differences between these classes of models by considering cosmological observations at low redshift. In particular, we analyse the redshift dependence of the fine structure constant and the proton to electron mass ratio in each of these scenarios. When the absorption lines belong to unscreened regions of space such as dwarf galaxies, a time variation would be present for chameleons. For both K-mouflage and Vainshtein mechanisms, the cosmological time variation of the scalar field is not suppressed in both unscreened and screened environments, therefore enhancing the variation of constants and their detection prospect. We also consider the time variation of the redshift of distant objects using their spectrocopic velocities. We find that models of the K-mouflage and Vainshtein types have very different spectroscopic velocities as a function of redshift and that their differences with the Λ-CDM template should be within reach of the future ELT-HIRES observations

  20. Chitosan microspheres in novel drug delivery systems.

    Science.gov (United States)

    Mitra, Analava; Dey, Baishakhi

    2011-07-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems.

  1. Silk Fibroin-Based Nanoparticles for Drug Delivery

    Science.gov (United States)

    Zhao, Zheng; Li, Yi; Xie, Mao-Bin

    2015-01-01

    Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By adjusting the particle size, the chemical structure and properties, the modified or recombinant SF-based nanoparticles can be designed to improve the therapeutic efficiency of drugs encapsulated into these nanoparticles. Therefore, they can be used to deliver small molecule drugs (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This paper reviews recent progress on SF-based nanoparticles, including chemical structure, properties, and preparation methods. In addition, the applications of SF-based nanoparticles as carriers for therapeutic drugs are also reviewed. PMID:25749470

  2. Do gastric contents modify antidotal efficacy of oral activated charcoal?

    Science.gov (United States)

    Olkkola, K T; Neuvonen, P J

    1984-01-01

    The effect of food on the antidotal efficacy of activated charcoal was studied in six healthy volunteers, who ingested aspirin 1000 mg, mexiletine 200 mg and tolfenamic acid 400 mg in a randomized cross-over study. Activated charcoal 25 g, suspended in water, was administered 5 min or 60 min after the drugs were taken on an empty stomach or after a standard meal. The serum concentrations and the cumulative excretion into urine of the drugs were followed for 48 h. When the drugs were taken on an empty stomach, activated charcoal given 5 min or 60 min afterwards reduced the bioavailability of the drugs by 75-98% or 10-60%, respectively. Food moderately weakened the effect of activated charcoal administered 5 min after the drugs, but when the charcoal was given 1 h later the effect was still practically the same, the reduction of absorption varying in both cases in the range of 45-85%. Thus the efficacy of charcoal given 60 min after the drugs was better after a standard meal than on an empty stomach. Presence of food in the stomach of patients with drug overdosage modifies the efficacy of activated charcoal and gives it more time to adsorb drugs in the gastrointestinal canal, possibly by slowing gastric emptying rate. PMID:6508975

  3. Targeting molecular networks for drug research

    Directory of Open Access Journals (Sweden)

    José Pedro Pinto

    2014-06-01

    Full Text Available The study of molecular networks has recently moved into the limelight of biomedical research. While it has certainly provided us with plenty of new insights into cellular mechanisms, the challenge now is how to modify or even restructure these networks. This is especially true for human diseases, which can be regarded as manifestations of distorted states of molecular networks. Of the possible interventions for altering networks, the use of drugs is presently the most feasible. In this mini-review, we present and discuss some exemplary approaches of how analysis of molecular interaction networks can contribute to pharmacology (e.g., by identifying new drug targets or prediction of drug side effects, as well as listing pointers to relevant resources and software to guide future research. We also outline recent progress in the use of drugs for in vitro reprogramming of cells, which constitutes an example par excellence for altering molecular interaction networks with drugs.

  4. Enhancing prescription drug innovation and adoption.

    Science.gov (United States)

    Alexander, G Caleb; O'Connor, Alec B; Stafford, Randall S

    2011-06-21

    The adoption and use of a new drug would ideally be guided by its innovation and cost-effectiveness. However, information about the relative efficacy and safety of a drug is typically incomplete even well after market entry, and various other forces create a marketplace in which most new drugs are little better than their older counterparts. Five proposed mechanisms are considered for promoting innovation and reducing the use of therapies ultimately found to offer poor value or have unacceptable risks. These changes range from increasing the evidence required for U.S. Food and Drug Administration approval to modifying the structure of drug reimbursement. Despite the challenges of policy implementation, the United States has a long history of successfully improving the societal value and safe use of prescription medicines.

  5. 21 CFR 172.894 - Modified cottonseed products intended for human consumption.

    Science.gov (United States)

    2010-04-01

    ... consumption. 172.894 Section 172.894 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.894 Modified cottonseed products...

  6. Sustained Release of a Water-Soluble Drug from Directly ...

    African Journals Online (AJOL)

    Okra gum was evaluated as a controlled-release agent in modified release matrices in comparison with sodium carboxymethylcellulose (NaCMC) using aspirin as the model drug. Tablets were produced by direct compression and the in vitro drug release was assessed under conditions similar to those in the gastrointestinal ...

  7. Contact lenses for ophthalmic drug delivery.

    Science.gov (United States)

    Hui, Alex

    2017-09-01

    Contact lenses as a means to deliver pharmaceuticals to the eye have seen a significant increase in research interest in the past few years. This review will detail the in vitro experiments which have investigated use of these contact lenses in the context of the desired pharmacological treatment goals in the management of infectious, inflammatory, allergic and glaucomatous diseases of the eye. The techniques researchers have employed to modify and tailor drug release rates from these materials, including the use of vitamin E diffusion barriers, modified ionicity, molecular imprinting and incorporation of drug reservoirs, will be discussed, as well as their impact on drug release kinetics. Finally, the demonstration of the feasibility of these materials when applied in vivo in animal models as well as in humans with and without disease will be presented and their results discussed relating to their implications for the future of the field. © 2017 Optometry Australia.

  8. MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    A. V. Zaborovskiy

    2017-01-01

    Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

  9. Modified General Relativity and Cosmology

    Science.gov (United States)

    Abdel-Rahman, A.-M. M.

    1997-10-01

    Aspects of the modified general relativity theory of Rastall, Al-Rawaf and Taha are discussed in both the radiation- and matter-dominated flat cosmological models. A nucleosynthesis constraint on the theory's free parameter is obtained and the implication for the age of the Universe is discussed. The consistency of the modified matter- dominated model with the neoclassical cosmological tests is demonstrated.

  10. Genetically modified foods and allergy.

    Science.gov (United States)

    Lee, T H; Ho, H K; Leung, T F

    2017-06-01

    2015 marked the 25th anniversary of the commercial use and availability of genetically modified crops. The area of planted biotech crops cultivated globally occupies a cumulative two billion hectares, equivalent to twice the land size of China or the United States. Foods derived from genetically modified plants are widely consumed in many countries and genetically modified soybean protein is extensively used in processed foods throughout the industrialised countries. Genetically modified food technology offers a possible solution to meet current and future challenges in food and medicine. Yet there is a strong undercurrent of anxiety that genetically modified foods are unsafe for human consumption, sometimes fuelled by criticisms based on little or no firm evidence. This has resulted in some countries turning away food destined for famine relief because of the perceived health risks of genetically modified foods. The major concerns include their possible allergenicity and toxicity despite the vigorous testing of genetically modified foods prior to marketing approval. It is imperative that scientists engage the public in a constructive evidence-based dialogue to address these concerns. At the same time, improved validated ways to test the safety of new foods should be developed. A post-launch strategy should be established routinely to allay concerns. Mandatory labelling of genetically modified ingredients should be adopted for the sake of transparency. Such ingredient listing and information facilitate tracing and recall if required.

  11. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  12. Bismuth nanoparticles-carbon nanotubes modified sensor for sulfasalazine analysis.

    Science.gov (United States)

    Nigović, Biljana; Jurić, Sandra; Mitrović, Iva

    2017-03-01

    Nanocomposite of bismuth nanoparticles and carbon nanotubes in Nafion matrix was used as modifier for glassy carbon electrode in analysis of anti-inflamatory drug sulfasalazine. The nanocomposite surface exhibited exceptional synergy and remarkable enhancement effect to the voltammetric response of drug. The surface morphology and structure characterization of the modified electrodes was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy and cyclic voltammetry. The sensor exhibited excellent electroanalytical performance for drug determination in comparison with bismuth film electrode. The adsorptive stripping square-wave voltammetric signal showed a good linear correlation to sulfasalazine concentration in a broad range from 5.0×10 -8 to 1.0×10 -5 M with low detection limit of 1.3×10 -8 M.The method was successfully utilised for drug quantification in human serum samples and good recoveries were obtained without interference from endogenous substances, 5-aminosalycilic acid and sulfapyridine formed after biotransformation of drug and folic acid co-administered as the supplement during sulfasalazine therapy. Additionally, the proposed sensor was successfully applied to analysis of sulfasalazine content in gastro-resistant pharmaceutical dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Drugs and lactation

    International Nuclear Information System (INIS)

    Kelssering, G.; Aguiar, L.F.; Ribeiro, R.M.; Souza, A.Z. de

    1988-01-01

    Different kinds of drugs who can be transferred through the mother's milk to the lactant and its effects are showed in this work. A list of them as below: cardiotonics, diuretics, anti-hypertensives, beta-blockings, anti-arrythmics, drugs with gastrintestinal tract action, hormones, antibiotics and chemotherapeutics, citostatic drugs, central nervous system action drugs and anticoagulants drugs. (L.M.J.) [pt

  14. Drugs Approved for Rhabdomyosarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  15. 99 Films on Drugs.

    Science.gov (United States)

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  16. Street Drugs and Pregnancy

    Science.gov (United States)

    ... drugs are bad for you, and they’re bad for your baby. About 1 in 20 women (5 percent) take street drugs during pregnancy. Street drugs include: Cocaine Ecstasy, methamphetamine and other club drugs Heroin Marijuana Prescription drugs that are abused How can street ...

  17. Modified Nanodiamonds for Detoxification

    Science.gov (United States)

    Gibson, Natalie Marie

    essential for interacting with charged molecules, like OTA. Furthermore, the increased ZPs lead to improved colloidal stabilities over a wide range of pH, which is important for their interaction in the GI tract. While the dyes and OTA illustrated primarily electrostatic adsorption mechanisms, neutrally charged AfB1's adsorption was predominantly based upon the aggregate size of the ND substrate. In addition to mycotoxins, fluorescent dyes, including propidium iodide, pyranine and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), were initially utilized during methodological development. Fluorescent dye investigations helped assesses the adsorption mechanisms of NDs and demonstrated the significance of electrostatic interactions. Beyond electrostatic adsorption mechanisms, surface functional groups were also responsible for the amount of dye adsorbed, as was also true in OTA adsorption. Therefore, surface characterization was carried out for several ND samples by FTIR, TOF-SIMS and TDMS analysis. Final results of our studies show that our modified NDs perform better than yeast cells walls and other NDs but comparable to activated charcoal in the adsorption of AfB1, and outperform clay minerals in OTA studies. Moreover, it was demonstrated that adsorption can be maintained in a wide range of pH, thereby, increasing the possibility of NDs use in mycotoxins enterosorbent applications.

  18. Evaluation of chemical modified hydrogel formulation for topical suitability.

    Science.gov (United States)

    Laffleur, Flavia

    2017-12-01

    Skin delivery and transdermal delivery are key ambitions of the pharmaceutical and cosmetically researchers. The study aimed to chemically modify well-known polymeric gelling agents in order to boost their topical suitability by fostering their dermal adhesiveness. Conventional chitosan was modified via amide bound formation with sulfhydryl compound thioglycolic acid. Subsequently, preactivated chitosan conjugate was established by preactivation of chitosan-thioglycolic acid with mercaptonicotinamide being covalently attached via disulfide bond linkage. All conjugates were examined due to their dermal adhesiveness and controlled drug release properties. Preactivated chitosan conjugates Exhibit 7.46-fold dermal adhesiveness on skin due to tensile adhesion strength. Furthermore a 1.9-fold controlled release of Rhodamine123 as model drug was determined in comparison to unmodified chitosan. Taken together, preactivated chitosan gels show a promising platform for topical application. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Directory of Open Access Journals (Sweden)

    Rodríguez de Lores Arnaiz Georgina

    2006-04-01

    Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process

  20. Attitudes towards drug legalization among drug users.

    Science.gov (United States)

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  1. Drug Development Process

    Science.gov (United States)

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  2. Drugs Approved for Leukemia

    Science.gov (United States)

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs ... used in leukemia that are not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) ...

  3. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  4. Teenagers and drugs

    Science.gov (United States)

    Teenagers and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... for a specialist who has experience working with teenagers. Do not hesitate, get help right away. The ...

  5. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  6. Value Modifier Public Use File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Center for Medicare (CM) has created a standard analytical file intended to promote transparency. For each Value Modifier performance year, CM will publish a...

  7. Nanocomposite thin films for triggerable drug delivery.

    Science.gov (United States)

    Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

    2018-05-01

    Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

  8. Classifying PML risk with disease modifying therapies.

    Science.gov (United States)

    Berger, Joseph R

    2017-02-01

    To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk. A method of contextualizing PML risk for DMTs is warranted. Classification of PML risk was predicated on three criteria:: 1) whether the underlying condition being treated predisposes to PML in the absence of the drug; 2) the latency from initiation of the drug to the development of PML; and 3) the frequency with which PML is observed. Among the DMTs, natalizumab occupies a place of its own with respect to PML risk. Significantly lesser degrees of risk exist for fingolimod and dimethyl fumarate. Whether PML will be observed with other DMTs in use for MS, such as, rituximab, teriflunomide, and alemtuzumab, remains uncertain. A logical classification for stratifying DMT PML risk is important for both the physician and patient in contextualizing risk/benefit ratios. As additional experience accumulates regarding PML and the DMTs, this early effort will undoubtedly require revisiting. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Text mining for drug-drug interaction.

    Science.gov (United States)

    Wu, Heng-Yi; Chiang, Chien-Wei; Li, Lang

    2014-01-01

    In order to understand the mechanisms of drug-drug interaction (DDI), the study of pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenetics (PG) data are significant. In recent years, drug PK parameters, drug interaction parameters, and PG data have been unevenly collected in different databases and published extensively in literature. Also the lack of an appropriate PK ontology and a well-annotated PK corpus, which provide the background knowledge and the criteria of determining DDI, respectively, lead to the difficulty of developing DDI text mining tools for PK data collection from the literature and data integration from multiple databases.To conquer the issues, we constructed a comprehensive pharmacokinetics ontology. It includes all aspects of in vitro pharmacokinetics experiments, in vivo pharmacokinetics studies, as well as drug metabolism and transportation enzymes. Using our pharmacokinetics ontology, a PK corpus was constructed to present four classes of pharmacokinetics abstracts: in vivo pharmacokinetics studies, in vivo pharmacogenetic studies, in vivo drug interaction studies, and in vitro drug interaction studies. A novel hierarchical three-level annotation scheme was proposed and implemented to tag key terms, drug interaction sentences, and drug interaction pairs. The utility of the pharmacokinetics ontology was demonstrated by annotating three pharmacokinetics studies; and the utility of the PK corpus was demonstrated by a drug interaction extraction text mining analysis.The pharmacokinetics ontology annotates both in vitro pharmacokinetics experiments and in vivo pharmacokinetics studies. The PK corpus is a highly valuable resource for the text mining of pharmacokinetics parameters and drug interactions.

  10. 75 FR 2926 - Pipeline Safety: Reporting Drug and Alcohol Test Results for Contractors and Multiple Operator...

    Science.gov (United States)

    2010-01-19

    .... PHMSA-2009-0408] Pipeline Safety: Reporting Drug and Alcohol Test Results for Contractors and Multiple... Materials Safety Administration (PHMSA), Office of Pipeline Safety (OPS), is modifying the Drug & Alcohol... begin collecting annual drug and alcohol testing data for contractor employees with Management...

  11. Biomimicry as a basis for drug discovery.

    Science.gov (United States)

    Kolb, V M

    1998-01-01

    Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term "natural product" is often used synonymously with "secondary metabolite." Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed "inventive evolution." It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products ("unnatural natural products"), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.

  12. Fighting the Drug War.

    Science.gov (United States)

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan…

  13. Drugs and Young People

    Science.gov (United States)

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  14. [Designer drugs in Finland].

    Science.gov (United States)

    Tacke, Ulrich; den Hollander, Bjørnar; Simojoki, Kaarlo; Korpi, Esa R; Pihlainen, Katja; Alho, Hannu

    2011-01-01

    Designer drugs are synthetic psychotropic drugs which are marketed as "legal drugs". Their emergence, rapid spreading and unpredictable effects have challenged the health and substance abuse care. The slow process of classification of an abusable drug has provided too many possibilities for spreading the designer drugs. Once a certain substance receives an illegal drugs classification, dealers and users usually move to another, slightly different molecule that is still legal. In Finland, the Narcotics Act has been amended to the effect that the addition of a new substance to the illegal drug list does not require an amendment to the law.

  15. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    Science.gov (United States)

    Hansen, J M; Christensen, L K

    1977-01-01

    The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

  16. Prodrug Strategy in Drug Development

    Directory of Open Access Journals (Sweden)

    Hajnal Kelemen

    2016-09-01

    Full Text Available Prodrugs are chemically modified derivatives introduced in therapy due to their advantageous physico-chemical properties (greater stability, improved solubility, increased permeability, used in inactive form. Biological effect is exerted by the active derivatives formed in organism through chemical transformation (biotransformation. Currently, 10% of pharmaceutical products are used as prodrugs, nearly half of them being converted to active form by hydrolysis, mainly by ester hydrolysis. The use of prodrugs aims to improve the bioavailability of compounds in order to resolve some unfavorable characteristics and to reduce first-pass metabolism. Other objectives are to increase drug absorption, to extend duration of action or to achieve a better tissue/organ selective transport in case of non-oral drug delivery forms. Prodrugs can be characterized by chemical structure, activation mechanism or through the presence of certain functional groups suitable for their preparation. Currently we distinguish in therapy traditional prodrugs prepared by chemical derivatisation, bioprecursors and targeted delivery systems. The present article is a review regarding the introduction and applications of prodrug design in various areas of drug development.

  17. Modifying Knowledge, Emotions, and Attitudes Regarding Genetically Modified Foods

    Science.gov (United States)

    Heddy, Benjamin C.; Danielson, Robert W.; Sinatra, Gale M.; Graham, Jesse

    2017-01-01

    The purpose of this study was to explore whether conceptual change predicted emotional and attitudinal change while learning about genetically modified foods (GMFs). Participants were 322 college students; half read a refutation text designed to shift conceptual knowledge, emotions, and attitudes, while the other half served as a control group.…

  18. Drug Products in the Medicaid Drug Rebate Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

  19. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  20. Effectiveness of permethrin standard and modified methods in scabies treatment

    Directory of Open Access Journals (Sweden)

    Saleha Sungkar

    2014-06-01

    Full Text Available Background: Permethrin is the drug of choice for scabies with side effects such as erythema, pain, itching and prickling sensation. Whole-body (standard topical application of permethrin causes discomfort; thus, modified application of permethrin to the lesion only, followed with baths twice daily using soap was proposed. The objective of the study is to know the effectiveness of standard against lesion-only application of permethrin in scabies treatment.Methods: An experimental study was conducted in pesantren in East Jakarta and data was collected in May-July 2012. Diagnosis of scabies was made through anamnesis and skin examination. Subjects positive for scabies were divided into three groups: one standard method group (whole-body topical application and two modified groups (lesion-only application followed by the use of regular soap and antiseptic soap group. The three groups were evaluated weekly for three consecutive weeks. Data was processed using SPSS 20 and analyzed by Kruskal-Wallis test.Results: Total of 94 subjects was scabies positive (prevalence 50% but only 69 subjects were randomly picked to be analyzed. The cure rate at the end of week III of the standard method group was 95.7%, modified treatment followed by the use of regular soap was 91.3%, and modified treatment followed by the use of antiseptic soap was 78.3% (p = 0.163. The recurrence rate of standard treatment was 8.7%,  modified treatment followed by the use of regular soap was 13% and modified treatment followed by the use of antiseptic soap was 26.1% (p = 0.250.Conclusion: The standard scabies treatment was as effective as the modified scabies treatment.

  1. [Designer drugs in Jutland].

    Science.gov (United States)

    Simonsen, K W; Kaa, E

    2001-04-16

    The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

  2. Summary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma

    DEFF Research Database (Denmark)

    Holgate, S T; Bousquet, J; Chung, K F

    2004-01-01

    With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, symptom preventers and disease modifying agents. Attention is drawn to the types of experimental eviden...

  3. Drug and xenobiotic biotransformation in the blood-brain barrier: A neglected issue.

    Directory of Open Access Journals (Sweden)

    José A.G. Agúndez

    2014-10-01

    Full Text Available Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to BBB as a drug-metabolizing barrier. The presence of drug metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying the drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.

  4. Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Zorica Djurić

    2012-10-01

    Full Text Available Implementation of the Quality by Design (QbD approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

  5. Calorimetric Study of Mesoporous SBA-15 Modified for Controlled Valproic Acid Delivery

    Directory of Open Access Journals (Sweden)

    Liliana Giraldo

    2013-01-01

    Full Text Available SBA-15 ordered mesoporous silica functionalized with (3-aminopropyltriethoxysilane (APTES was used as the carrier for anticonvulsant drug 2-propylpentanoic acid (valproic acid. The surface of SBA-15 containing free silanol groups was modified with 3-aminopropyltriethoxysilane via postsynthetic reaction. Functionalization of the carrier with basic aminopropyl groups resulted in an ionic interaction with acidic valproic acid. The samples of carriers and carrier-drug complexes were characterized by elemental analysis, N2 adsorption, FTIR, and UV spectroscopy. The adsorption of valproic acid on modified mesoporous matrix was proportional to the amount of introduced aminopropyl groups. A thermodynamic study with isothermal titration calorimetry (ITC was made to characterize the modification and encapsulation of SBA-15 with APTES and valproic acid, respectively. The maximum content of deposited drug in modified SBA-15 was close to 30 wt.%. Tests performed in acidic solution (pH 2.0 showed the best pharmaceutical availability.

  6. Medicaid Drug Rebate Program Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Product Data for Drugs in the Medicaid Drug Rebate Program. The rebate drug product data file contains the active drugs that have been reported by participating drug...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Cigs Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse ... the United States. Drugs can change the way the brain works, disrupting the parts of the brain that ...

  9. Understanding Drug Use and Addiction

    Science.gov (United States)

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... factors affect drug use trends, when young people view drug use as harmful, they tend to decrease ...

  10. Food-drug interactions

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated......, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers...... are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those...

  11. Jogging Can Modify Disruptive Behaviors.

    Science.gov (United States)

    Allen, Jill I.

    1980-01-01

    Jogging was used to modify disruptive behavior as part of the classroom routine for 12 learning disabled elementary-grade boys. The number of incidents of each of five negative behaviors were reduced by half following the 10-minute jogging routine. (SBH)

  12. Modified gravity without dark matter

    NARCIS (Netherlands)

    Sanders, Robert; Papantonopoulos, L

    2007-01-01

    On an empirical level, the most successful alternative to dark matter in bound gravitational systems is the modified Newtonian dynamics, or MOND, proposed by Milgrom. Here I discuss the attempts to formulate MOND as a modification of General Relativity. I begin with a summary of the phenomenological

  13. Modified Steiner functional string action

    International Nuclear Information System (INIS)

    Baillie, C.F.; Johnston, D.A.

    1992-01-01

    It has recently been suggested by Ambartzumian et al. that the modified Steiner functional has desirable properties as an action for random surfaces and hence string world sheets. We perform a simulation of this action on a dynamically triangulated random surface to investigate this claim and find that the surfaces are in a flat phase

  14. Polymeric Micro- and Nanofabricatced Devices for Oral Drug Delivery

    Science.gov (United States)

    Fox, Cade Brylee

    While oral drug administration is by far the most preferred route, it is accompanied by many barriers that limit drug uptake such as the low pH of the stomach, metabolic and proteolytic enzymes, and limited permeability of the intestinal epithelium. As a result, many drugs ranging from small molecules to biological therapeutics have limited oral bioavailability, precluding them from oral administration. To address this issue, microfabrication has been applied to create planar, asymmetric devices capable of binding to the lining of the gastrointestinal tract and releasing drug at high concentrations, thereby increasing oral drug uptake. While the efficacy of these devices has been validated in vitro and in vivo, modifying their surfaces with nanoscale features has potential to refine their properties for enhanced drug delivery. This dissertation first presents an approach to fabricate polymeric microdevices coated with nanowires in a rapid, high throughput manner. The nanowires demonstrate rapid drug localization onto the surface of these devices via capillary action and increased adhesion to epithelial tissue, suggesting that this fabrication technique can be used to create devices with enhanced properties for oral drug delivery. Also presented are microdevices sealed with nanostraw membranes. The nanostraw membranes provide sustained drug release by limiting drug efflux from the devices, prevent drug degradation by limiting influx of outside biomolecules, and enhance device bioadhesion by penetrating into the mucus layer of the intestinal lining. Finally, an approach that dramatically increases the capacity and efficiency of drug loading into microdevices over previous methods is presented. A picoliter-volume printer is used to print drug directly into device reservoirs in an automated fashion. The technologies presented here expand the capabilities of microdevices for oral drug delivery by incorporating nanoscale structures that enhance device bioadhesion

  15. ASTHME INFANTILE: Les facteurs de risque modifiables ...

    African Journals Online (AJOL)

    MOTS CLES: Asthme - Infantile - Facteurs de risque - Modifiables. CHILDHOOD ASTHMA: Modifiable risk factors. ABSTRACT: This cross sectional study was carried out to determine the modifiable risk factors, for which some intervention could modify the evolution of childhood asthma. To do this, 145 children aged 3 ...

  16. Drugs and drug policy in the Netherlands

    NARCIS (Netherlands)

    Leuw, Ed.

    1991-01-01

    The Dutch parliament enacted the revised Opium Act in 1976. This penal law is part of the Dutch drug policy framework that includes tolerance for nonconforming lifestyles, risk reduction in regard to the harmful health and social consequences of drug taking, and penal measures directed against

  17. MODIFIED TECHNIQUE OF TOTAL LARYNGECTOMY

    Directory of Open Access Journals (Sweden)

    Predrag Spirić

    2010-12-01

    Full Text Available Surgical technique of total laryngectomy is well presented in many surgical textbooks. Essentially, it has remained the same since Gluck an Soerensen in 1922 described all its details. Generally, it stresses the U shape skin incision with releasing laryngeal structures and removing larynx from up to down. Further, pharyngeal reconstruction is performed with different kinds of sutures in two or more layers and is finished with skin suture and suction drainage. One of worst complications following this surgery is pharyngocutaneous fistula (PF. Modifications proposed in this this article suggests vertical skin incision with larynx removal from below upwards. In pharyngeal reconstruction we used the running locked suture in submucosal plan with „tobacco sac“ at the end on the tongue base instead of traditional T shaped suture. Suction drains were not used.The aim of study was to present the modified surgical technique of total laryingectomy and its impact on hospital stay duration and pharyngocutanous fistula formation. In this randomized study we analyzed 49 patients operated with modified surgical technique compared to 49 patient operated with traditional surgical technique of total laryngectomy. The modified technique of total laryngectomy was presented. Using modified technique we managed to decrease the PF percentage from previous 20,41% to acceptable 8,16% (p=0,0334. Also, the average hospital stay was shortened from 14,96 to 10,63 days (t =-2.9850; p=0.0358.The modified technique of total laryngectomy is safe, short and efficient surgical intervention which decreases the number of pharyngocutaneos fistulas and shortens the hospital stay.

  18. Genetically Modified Agrifood Trade: Necessity Or Concerns?

    OpenAIRE

    Nurliza, Nurliza

    2013-01-01

    Genetically modified agri-foods are genetically modified using biotechnology. Genetically modified organisms (GMOs) advantages are the focus of much attention in world food markets. Genetically modified crop technology is claimed also to have great potential for the world€™s farmers and ultimately consumers, following initial success with genetically modified cotton varieties. Benefits for farmers could include greater productivity and less occupational health and environmental damage (e.g., ...

  19. IMPROVING ACCESS TO DRUGS

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2012-11-01

    Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs

  20. Properties of diclofenac sodium sorption onto natural zeolite modified with cetylpyridinium chloride.

    Science.gov (United States)

    Krajišnik, Danina; Daković, Aleksandra; Milojević, Maja; Malenović, Anđelija; Kragović, Milan; Bogdanović, Danica Bajuk; Dondur, Vera; Milić, Jela

    2011-03-01

    In this study an investigation of a model drug sorption onto cationic surfactant-modified natural zeolites as a drug formulation excipient was performed. Natural zeolite was modified with cetylpyridinium chloride in amounts equivalent to 100, 200 and 300% of its external cation-exchange capacity. The starting material and obtained organozeolites were characterized by Fourier transform infrared spectroscopy, zeta potential measurements and thermal analysis. In vitro sorption of diclofenac sodium as a model drug was studied for all surfactant/zeolite composites by means of sorption isotherm measurements in aqueous solutions (pH 7.4). The modified zeolites with three levels of surfactant coverage within the short activation time were prepared. Zeta potential measurements and thermal analysis showed that when the surfactant loading level was equal to external cation-exchange value, almost monolayer of organic phase were present at the zeolitic surface while higher amounts of surfactant produced less extended bilayers, ordered bilayers or admicelles at the zeolitic surface. Modified zeolites, obtained in this manner, were effective in diclofenac sodium sorption and the organic phase derived from adsorbed cetylpyridinium chloride was the primary sorption phase for the model drug. The Langmuir isotherm was found to describe the equilibrium sorption data well over the entire concentration range. The separate contributions of the adsorption and partition to the total sorption of DS were analyzed mathematically. Results revealed that that adsorption and partitioning of the model drug take place simultaneously. 2010 Elsevier B.V. All rights reserved.

  1. Adverse drug reactions in hospitalized Colombian children.

    Science.gov (United States)

    de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

    2016-09-30

    The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p = 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p = 0.005). Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.

  2. In vitro and in vivo anticancer activity of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles.

    Science.gov (United States)

    Venkatasubbu, G Devanand; Ramasamy, S; Reddy, G Pramod; Kumar, J

    2013-08-01

    Targeted drug delivery using nanocrystalline materials delivers the drug at the diseased site. This increases the efficacy of the drug in killing the cancer cells. Surface modifications were done to target the drug to a particular receptor on the cell surface. This paper reports synthesis of hydroxyapatite and titanium dioxide nanoparticles and modification of their surface with polyethylene glycol (PEG) followed by folic acid (FA). Paclitaxel, an anticancer drug, is attached to functionalized hydroxyapatite and titanium dioxide nanoparticles. The pure and functionalised nanoparticles are characterised with XRD, TEM and UV spectroscopy. Anticancer analysis was carried out in DEN induced hepatocarcinoma animals. Biochemical, hematological and histopathological analysis show that the surface modified paclitaxel attached nanoparticles have an higher anticancer activity than the pure paclitaxel and surface modified nanoparticles without paclitaxel. This is due to the targeting of the drug to the folate receptor in the cancer cells.

  3. Drug-drug interactions : from knowledge base to clinical impact

    OpenAIRE

    Andersson, Marine

    2014-01-01

    Drug usage has increased steadily, and the more drugs used, the higher the risk for adverse effects or loss of effect due to drug-drug interactions. For drug prescribers it is difficult to know what drugs a patient is taking and whether they interact. Computerizing of health care records has made it possible to connect patients’ drug lists to clinical decision support systems giving the prescriber information about e.g. drug-drug interactions, duplicated prescriptions and ...

  4. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  5. CMS Drug Spending

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS has released several information products that provide spending information for prescription drugs in the Medicare and Medicaid programs. The CMS Drug Spending...

  6. Prescription Drug Abuse

    Science.gov (United States)

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include opioids, sedatives, ...

  7. Prescription Drug Profiles PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This release contains the Prescription Drug Profiles Public Use Files (PUFs) drawn from Medicare prescription drug claims for the year of the date on which the...

  8. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  9. Drugs to be Discontinued

    Data.gov (United States)

    U.S. Department of Health & Human Services — Companies are required under Section 506C of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (as amended by the Food and Drug Administration Safety and...

  10. Drug AMP Reporting - Quarterly

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drugs that have been reported under the Medicaid Drug Rebate Program along with an indication of whether or not the required Average Manufacturer Price (AMP) was...

  11. National Drug IQ Challenge

    Science.gov (United States)

    ... National Drug IQ Challenge 2017 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2016 National Drug IQ Challenge 2016 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2015 ...

  12. Medication/Drug Allergy

    Science.gov (United States)

    ... Training Home Conditions Medication/Drug Allergy Medication/Drug Allergy Make an Appointment Find a Doctor Ask a ... risk for adverse reactions to medications. Facts about Allergies The tendency to develop allergies may be inherited. ...

  13. Use of a novel modified TSI for the evaluation of controlled-release aerosol formulations. I.

    Science.gov (United States)

    McConville, J T; Patel, N; Ditchburn, N; Tobyn, M J; Staniforth, J N; Woodcock, P

    2000-11-01

    When considering the development of potential controlled-release pulmonary drug delivery systems, there is at present no standard method available for the assessment of in vitro drug release profiles necessary to understand how the drug might release following deposition in the lungs. For this purpose, the twin-stage impinger (TSI), apparatus A of the BP, has been redesigned and tested. This modified TSI was found capable of discriminating between drug release rates from conventional and different dry powder formulations consisting of model controlled-release excipients, providing information related to (a) drug diffusion properties of controlled-release dry powder blends with different excipient components and (b) the effect of varying drug concentration within a given formulation.

  14. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids

    2002-01-01

    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... of pharmacologically active substances or specific products for the treatment of sexual dysfunction such as sildenafil. Above all, it should be acknowledged that relatively few data are available in this field and in particular that there is a lack of controlled studies....... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  15. Detection Progress of Selected Drugs in TLC

    Science.gov (United States)

    Pyka, Alina

    2014-01-01

    This entry describes applications of known indicators and dyes as new visualizing reagents and various visualizing systems as well as photocatalytic reactions and bioautography method for the detection of bioactive compounds including drugs and compounds isolated from herbal extracts. Broadening index, detection index, characteristics of densitometric band, modified contrast index, limit of detection, densitometric visualizing index, and linearity range of detected compounds were used for the evaluation of visualizing effects of applied visualizing reagents. It was shown that visualizing effect depends on the chemical structure of the visualizing reagent, the structure of the substance detected, and the chromatographic adsorbent applied. The usefulness of densitometry to direct detection of some drugs was also shown. Quoted papers indicate the detection progress of selected drugs investigated by thin-layer chromatography (TLC). PMID:24551853

  16. Drug Delivery Nanoparticles in Skin Cancers

    Science.gov (United States)

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  17. Drug Delivery Nanoparticles in Skin Cancers

    Directory of Open Access Journals (Sweden)

    Chiara Dianzani

    2014-01-01

    Full Text Available Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported.

  18. Understanding Drug Release Data through Thermodynamic Analysis

    Directory of Open Access Journals (Sweden)

    Marjorie Caroline Liberato Cavalcanti Freire

    2017-06-01

    Full Text Available Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

  19. Understanding Drug Release Data through Thermodynamic Analysis

    Science.gov (United States)

    Freire, Marjorie Caroline Liberato Cavalcanti; Alexandrino, Francisco; Marcelino, Henrique Rodrigues; Picciani, Paulo Henrique de Souza; Silva, Kattya Gyselle de Holanda e; Genre, Julieta; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Sócrates Tabosa

    2017-01-01

    Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability. PMID:28773009

  20. Endoperoxide Drug Cross-Resistance Patterns for Plasmodium falciparum Exhibiting an Artemisinin Delayed-Clearance Phenotype.

    Science.gov (United States)

    Siriwardana, A; Iyengar, K; Roepe, P D

    2016-11-01

    The ring-stage susceptibility assay was modified to quantify the susceptibilities of multiple strains of control and delayed-clearance phenotype (DCP) Plasmodium falciparum strains to seven endoperoxide antimalarial drugs. The susceptibility of all of the DCP lines to six of the drugs was lower than that of the controls. In contrast, DCP parasites did not show reduced susceptibility to the synthetic endoperoxide drug OZ439. These data show that it is possible to circumvent emerging artemisinin resistance with a modified endoperoxide drug. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. Sociology of Drug Consumption

    OpenAIRE

    2004-01-01

    In this article which is a review of sociological ideas and studies of drug abusers in social situation, drug addiction steps (particularly alcohol, heroin and cocaine consumption) are revised and some explanations are made. Also, the role of some sociological ideas in drug addiction is considered in which Anomie Theory reads: "because of such duality, the individuals who are not satisfied with their role are in hurt." According to this theory, drug users choose seclusion and neglecting usual...

  2. Drugs in sport

    OpenAIRE

    Robinson, D

    2007-01-01

    This new edition includes fresh information regarding drugs use and abuse in sport and the updated worldwide anti-doping laws, and changes to the prohibited and therapeutic use exemption lists. The objectives of the book are to review/discuss the latest information on drugs in sport by considering i) actions of drugs and hormones, ii) medication and nutritional supplements in sport, iii) the latest doping control regulations of the WADA, iv) the use of banned therapeutic drugs in sport, v) an...

  3. The War on Drugs is Counterproductive, Once Again

    Directory of Open Access Journals (Sweden)

    Carlos Humberto Ortiz

    2009-12-01

    Full Text Available A two-sector general equilibrium model that included drugs as basic goods was relativelysuccessful at explaining the waste of resources that the war on drugs incurs (Ortiz, 2003. Due to theassumption of constant productivity, the model predicted the rise of the drug price with supplyrepression. Yet Plan Colombia, an unparalleled effort to eradicate drug production in Colombia,had no significant effect on drug prices. In order to correct the model two sources of productivityimprovement in the drugs sector are examined. The modified model helps to understand why drugprices have remained stable, why global supply and demand have not diminished, and why cocaplantations were spread throughout the nation under Plan Colombia.

  4. Rural drug users: factors associated with substance abuse treatment utilization.

    Science.gov (United States)

    Oser, Carrie B; Leukefeld, Carl G; Tindall, Michele Staton; Garrity, Thomas F; Carlson, Robert G; Falck, Russel; Wang, Jichuan; Booth, Brenda M

    2011-06-01

    The purpose of this study is to use a modified version of Andersen's Behavioral Model of Health Services Use to identify the correlates of the number of substance abuse treatment episodes received by rural drug users. Data were collected from face-to-face interviews with 711 drug users in rural areas of Ohio, Arkansas, and Kentucky. Descriptive analyses examine rural drug users' substance use histories and retrospective substance abuse treatment service utilization patterns. A negative binomial regression model indicated that selected predisposing, historical health, and enabling factors were significantly associated with the utilization of substance abuse treatment among rural drug users. Despite high levels of recent and lifetime self-reported substance use among these rural drug users, treatment services were underutilized. Future studies are needed to examine the impact of the health care system and characteristics of the external environment associated with rural substance abuse treatment in order to increase utilization among drug users.

  5. Conduct Disorder Symptoms and Illicit Drug Use in Juvenile Justice Involved Youth: The Reciprocal Relationship Between Positive Illicit Drug-Use Attitudes and Illicit Drug Use.

    Science.gov (United States)

    Kolp, Haley M; Hershberger, Alexandra R; Sanders, Jasmyn; Um, Miji; Aalsma, Matthew; Cyders, Melissa A

    2017-11-29

    Conduct disorder (CD) symptoms cooccur at high rates with illicit drug use in juvenile justice involved youth, which results in poorer outcomes; however, research has not identified where best to intervene in this relationship, limiting the identification of modifiable risk factors to reduce negative effects of CD symptoms. Two mediation models were examined to investigate the potential for CD symptoms to influence a reciprocal relationship between illicit drug use and positive drug attitudes, controlling for age, gender, and race. Data were examined for 245 juvenile justice involved youth (mean age = 15.46, SD = 1.30, range 12-18, 64.9% Black, 80.4% male) who completed court-ordered psychological assessments. Findings indicate: (1) Positive attitudes toward illicit drug use significantly mediated the relationship between CD symptoms and illicit drug use (β = 0.16, CI 0.09-0.27; test for indirect effect z = 4.17, p drug use significantly mediated the relationship between CD symptoms and positive attitudes toward illicit drug use (β = 0.20, CI 0.12-0.32; test for indirect effect z = 4.87, p drug use both indirectly, through more positive attitudes toward illicit drug use, and directly, which further strengthens positive attitudes toward illicit drug use.

  6. Nanoparticles Modified ITO Based Biosensor

    Science.gov (United States)

    Khan, M. Z. H.

    2017-04-01

    Incorporation of nanomaterials with controlled molecular architecture shows great promise in improving electronic communication between biomolecules and the electrode substrate. In electrochemical applications metal nanoparticles (NPs) modified electrodes have been widely used and are emerging as candidates to develop highly sensitive electrochemical sensors. There has been a growing technological interest in modified indium tin oxide (ITO) electrodes due to their prominent optoelectronic properties and their wide use as a transducing platform. The introduction of NPs into the transducing platform is commonly achieved by their adsorption onto conventional electrode surfaces in various forms, including that of a composite. The aim of this review is to discuss the role of metallic NPs for surface fabrication of ITO thin films leading to detection of specific biomolecules and applications as a biosensor platform.

  7. Complexation thermodynamics of modified cyclodextrins

    DEFF Research Database (Denmark)

    Schönbeck, Jens Christian Sidney; Westh, Peter; Holm, Rene

    2014-01-01

    Inclusion complexes between two bile salts and a range of differently methylated β-cyclodextrins were studied in an attempt to rationalize the complexation thermodynamics of modified cyclodextrins. Calorimetric titrations at a range of temperatures provided precise values of the enthalpies (ΔH......°), entropies (ΔS°), and heat capacities (ΔCp) of complexation, while molecular dynamics simulations assisted the interpretation of the obtained thermodynamic parameters. As previously observed for several types of modified cyclodextrins, the substituents at the rims of the cyclodextrin induced large changes......° and then a strong decrease when the degree of substitution exceeded some threshold. Exactly the same trend was observed for ΔCp. The dehydration of nonpolar surface, as quantified by the simulations, can to a large extent explain the variation in the thermodynamic parameters. The methyl substituents form additional...

  8. Impedance of electrochemically modified graphite.

    Science.gov (United States)

    Magdić, Katja; Kvastek, Krešimir; Horvat-Radošević, Višnja

    2014-01-01

    Electrochemical impedance spectroscopy, EIS, has been applied for characterization of electrochemically modified graphite electrodes in the sulphuric acid solution. Graphite modifications were performed by potential cyclization between potentials of graphite oxide formation/reduction, different number of cycles, and prolonged reduction steps after cyclization. Impedance spectra measured at two potential points within double-layer region of graphite have been successfully modeled using the concept of porous electrodes involving two different electrolyte diffusion paths, indicating existence of two classes of pores. The evaluated impedance parameter values show continuous changes with stages of graphite modification, indicating continuous structural changes of pores by number of potential cycles applied. Differences of impedance parameter values at two potential values indicate the potential induced changes of solution properties within the pores of modified graphite.

  9. Generalized gravity from modified DFT

    Energy Technology Data Exchange (ETDEWEB)

    Sakatani, Yuho [Department of Physics, Kyoto Prefectural University of Medicine,Kyoto 606-0823 (Japan); Fields, Gravity and Strings, CTPU,Institute for Basic Sciences, Daejeon 34047 (Korea, Republic of); Uehara, Shozo [Department of Physics, Kyoto Prefectural University of Medicine,Kyoto 606-0823 (Japan); Yoshida, Kentaroh [Department of Physics, Kyoto University,Kitashirakawa Oiwake-cho, Kyoto 606-8502 (Japan)

    2017-04-20

    Recently, generalized equations of type IIB supergravity have been derived from the requirement of classical kappa-symmetry of type IIB superstring theory in the Green-Schwarz formulation. These equations are covariant under generalized T-duality transformations and hence one may expect a formulation similar to double field theory (DFT). In this paper, we consider a modification of the DFT equations of motion by relaxing a condition for the generalized covariant derivative with an extra generalized vector. In this modified double field theory (mDFT), we show that the flatness condition of the modified generalized Ricci tensor leads to the NS-NS part of the generalized equations of type IIB supergravity. In particular, the extra vector fields appearing in the generalized equations correspond to the extra generalized vector in mDFT. We also discuss duality symmetries and a modification of the string charge in mDFT.

  10. Drugs of Abuse.

    Science.gov (United States)

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  11. Drug Enforcement Administration.

    Science.gov (United States)

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  12. Immediate Drug Hypersensitivity.

    Science.gov (United States)

    Wickner, Paige G; Hong, David

    2016-07-01

    Drug allergy affects a large percentage of the general population. A listed drug allergy can also have broad implications for many aspects of patient care. Here, we will review recent advances in the arena of drug allergies with a focus on antibiotics, monoclonals, NSAIDs, and chemotherapeutics.

  13. Writing Drug Cultures

    DEFF Research Database (Denmark)

    Nissen, Morten

    2012-01-01

    The paper juxtaposes the cultural mediation of experience through drugs with that performed with text. As a sample of the currently radically changing relations between professional and lay knowledge in the field of drug interventions, the website of a Copenhagen institution for young drug users...

  14. Drug and Substance Abuse

    Science.gov (United States)

    ... Basic Facts & Information What does “Drug and Substance Abuse” mean? Most drugs and other chemical substances are helpful when used ... medications, and pain medications. Some older adults also abuse illegal drugs, including marijuana, cocaine, hallucinogens, and injected narcotics. Some ...

  15. Dynamics of Drug Use

    Science.gov (United States)

    Rollins, Joan H.; Holden, Raymond H.

    1977-01-01

    This paper analyzes data from interviews with 167 drug users in the community, including age, sex, birth order, education, family constellation, and circumstances of first drug use. The majority of subjects had tried to stop using drugs, but most had been unsuccessful at the time of the interview. (Author)

  16. Cutaneous adverse drug reactions

    African Journals Online (AJOL)

    limiting but they can be the initial presentation of more serious reactions such as Stevens-Johnson and drug hypersensitivity syndromes.3 It is thus important for the clinician to distinguish between self-limiting morbilliform drug eruptions that resolve solely with the withdrawal of the offending drug and the life-threatening ...

  17. Drugs in sport

    National Research Council Canada - National Science Library

    Mottram, D. R. (David R.)

    2005-01-01

    ...-Doping Agency (WADA) Methods and advances in doping control, and the sanctions for testing positive The use of therapeutic drugs banned in sport Evaluation of the status of creatine as a legitimate nutritional supplement Ethical, political and administrative issues in monitoring drug use An assessment of the prevalence of drug taking in sp...

  18. DRUG INTERACTIONS WITH TUBERCULOSIS THERAPY

    African Journals Online (AJOL)

    Kurt

    The most important adverse drug-drug interactions occur with drugs that have seri- ous toxicity and a low therapeutic index, where relatively small changes in drug level can have significant adverse consequences. Additionally, drug-drug interac- tions can be clinically important if the disease being controlled with the drug is.

  19. Black Youths and Illegal Drugs.

    Science.gov (United States)

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  20. QGP and Modified Jet Fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin-Nian

    2005-04-18

    Recent progresses in the study of jet modification in hotmedium and their consequences in high-energy heavy-ion collisions are reviewed. In particular, I will discuss energy loss for propagating heavy quarks and the resulting modified fragmentation function. Medium modification of the parton fragmentation function due to quark recombination are formulated within finite temperature field theory and their implication on the search for deconfined quark-gluon plasma is also discussed.

  1. Political Subculture: A Resilience Modifier

    Science.gov (United States)

    2011-09-01

    A RESILIENCE MODIFIER by Gordon S. Hunter September 2011 Thesis Advisor: Samuel H. Clovis , Jr. Second Reader...Approved by: Samuel H. Clovis , Jr., DPA Thesis Advisor Lauren S. Fernandez, DSc Second Reader Harold A. Trinkunas, PhD Chair...addition, I must acknowledge the continued support, guidance, and encouragement of Dr. Sam Clovis and Dr. Lauren Fernandez who have led me on the path to

  2. Estimating the Modified Allan Variance

    Science.gov (United States)

    Greenhall, Charles

    1995-01-01

    The third-difference approach to modified Allan variance (MVAR) leads to a tractable formula for a measure of MVAR estimator confidence, the equivalent degrees of freedom (edf), in the presence of power-law phase noise. The effect of estimation stride on edf is tabulated. A simple approximation for edf is given, and its errors are tabulated. A theorem allowing conservative estimates of edf in the presence of compound noise processes is given.

  3. Genetically modified plants for law enforcement applications

    Science.gov (United States)

    Stewart, C. Neal, Jr.

    2002-08-01

    Plants are ubiquitous in the environment and have the unique ability to respond to their environment physiologically and through altered gene expression profiles (they cannot walk away). In addition, plant genetic transformation techniques and genomic information in plants are becoming increasingly advanced. We have been performing research to express the jellyfish green fluorescent protein (GFP) in plants. GFP emits green light when excited by blue or UV light. In addition, my group and collaborators have developed methods to detect GFP in plants by contact instruments and at a standoff. There are several law enforcement applications for this technology. One involves using tagging and perhaps modifying drug plants genetically. In one instance, we could tag them for destruction. In another, we could adulterate them directly. Another application is one that falls into the chemical terrorism and bioterrorism countermeasures category. We are developing plants to sense toxins and whole organisms covertly. Plants are well adapted to monitor large geographic areas; biosurveillance. Some examples of research being performed focus on plants with plant pathogen inducible promoters fused to GFP for disease sensing, and algae biosensors for chemicals.

  4. Genetically modified bacteriophages in applied microbiology.

    Science.gov (United States)

    Bárdy, P; Pantůček, R; Benešík, M; Doškař, J

    2016-09-01

    Bacteriophages represent a simple viral model of basic research with many possibilities for practical application. Due to their ability to infect and kill bacteria, their potential in the treatment of bacterial infection has been examined since their discovery. With advances in molecular biology and gene engineering, the phage application spectrum has been expanded to various medical and biotechnological fields. The construction of bacteriophages with an extended host range or longer viability in the mammalian bloodstream enhances their potential as an alternative to conventional antibiotic treatment. Insertion of active depolymerase genes to their genomes can enforce the biofilm disposal. They can also be engineered to transfer various compounds to the eukaryotic organisms and the bacterial culture, applicable for the vaccine, drug or gene delivery. Phage recombinant lytic enzymes can be applied as enzybiotics in medicine as well as in biotechnology for pathogen detection or programmed cell death in bacterial expression strains. Besides, modified bacteriophages with high specificity can be applied as bioprobes in detection tools to estimate the presence of pathogens in food industry, or utilized in the control of food-borne pathogens as part of the constructed phage-based biosorbents. © 2016 The Society for Applied Microbiology.

  5. Formulation approaches in mitigating toxicity of orally administrated drugs.

    Science.gov (United States)

    Kadiyala, Irina; Tan, Elijah

    2013-01-01

    This paper provides an overview of current formulation approaches to mitigate toxicity of orally administrated drugs. The formulation approaches are characterized by their intended impact on a drug's pharmacokinetic parameters, pharmacological properties or metabolic pathways. Regulatory opportunities and constraints with focus on U.S. regulations in optimizing a drug's safety or efficacy profile are reviewed. The following formulation approaches are described: (i) pharmacokinetic-modulating and (ii) pharmacodynamic-modulating. In the pharmacokinetic-modulating approach, the pharmacokinetic profile of drug release is modified by, for example, a reduction in peak drug plasma concentration while preserving or improving AUC, thereby potentially reducing toxic effects that may be related to C(max). In the pharmacodynamic-modulating approach, the drug is co-dosed with pharmacologically active or nonpharmacologically active agent or agents intended for mitigation of the drug's toxicity. The pharmacodynamic-modulating approach requires information on the specificity of drug interactions with other compounds and also on metabolic pathways. Examples demonstrating successful formulation work in reducing drug toxicity are provided. The in-depth knowledge of the drug's PK and PD properties combined with a greater understanding of the biology of diseases are necessary for successful drug product formulation leading to optimized in vivo exposure and minimized toxicity.

  6. Increased cellular uptake of peptide-modified PEGylated gold nanoparticles.

    Science.gov (United States)

    He, Bo; Yang, Dan; Qin, Mengmeng; Zhang, Yuan; He, Bing; Dai, Wenbing; Wang, Xueqing; Zhang, Qiang; Zhang, Hua; Yin, Changcheng

    2017-12-09

    Gold nanoparticles are promising drug delivery vehicles for nucleic acids, small molecules, and proteins, allowing various modifications on the particle surface. However, the instability and low bioavailability of gold nanoparticles compromise their clinical application. Here, we functionalized gold nanoparticles with CPP fragments (CALNNPFVYLI, CALRRRRRRRR) through sulfhydryl PEG to increase their stability and bioavailability. The resulting gold nanoparticles were characterized with transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectrometry and X-ray photoelectron spectroscopy (XPS), and the stability in biological solutions was evaluated. Comparing to PEGylated gold nanoparticles, CPP (CALNNPFVYLI, CALRRRRRRRR)-modified gold nanoparticles showed 46 folds increase in cellular uptake in A549 and B16 cell lines, as evidenced by the inductively coupled plasma atomic emission spectroscopy (ICP-AES). The interactions between gold nanoparticles and liposomes indicated CPP-modified gold nanoparticles bind to cell membrane more effectively than PEGylated gold nanoparticles. Surface plasmon resonance (SPR) was used to measure interactions between nanoparticles and the membrane. TEM and uptake inhibitor experiments indicated that the cellular entry of gold nanoparticles was mediated by clathrin and macropinocytosis. Other energy independent endocytosis pathways were also identified. Our work revealed a new strategy to modify gold nanoparticles with CPP and illustrated the cellular uptake pathway of CPP-modified gold nanoparticles. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Comparative in silico profiling of epigenetic modifiers in human tissues.

    Science.gov (United States)

    Son, Mi-Young; Jung, Cho-Rok; Kim, Dae-Soo; Cho, Hyun-Soo

    2018-04-06

    The technology of tissue differentiation from human pluripotent stem cells has attracted attention as a useful resource for regenerative medicine, disease modeling and drug development. Recent studies have suggested various key factors and specific culture methods to improve the successful tissue differentiation and efficient generation of human induced pluripotent stem cells. Among these methods, epigenetic regulation and epigenetic signatures are regarded as an important hurdle to overcome during reprogramming and differentiation. Thus, in this study, we developed an in silico epigenetic panel and performed a comparative analysis of epigenetic modifiers in the RNA-seq results of 32 human tissues. We demonstrated that an in silico epigenetic panel can identify epigenetic modifiers in order to overcome epigenetic barriers to tissue-specific differentiation.

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/ ...

  9. Drug interactions with sunitinib.

    Science.gov (United States)

    Bilbao-Meseguer, Idoia; Jose, Begoña San; Lopez-Gimenez, Leocadio R; Gil, Maria A; Serrano, Laura; Castaño, Mikel; Sautua, Saioa; Basagoiti, Amaya De; Belaustegui, Ainhoa; Baza, Beatriz; Baskaran, Zuriñe; Bustinza, Alazne

    2015-02-01

    Sunitinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumor, advanced renal cell carcinoma, and pancreatic neuroendocrine tumors. The aim of this article is to describe the pharmacological interactions between sunitinib and commonly prescribed drugs. We reviewed available information on pharmacological interactions between sunitinib and concomitantly prescribed drugs. Drugs were grouped into different therapeutic groups according to the Anatomical Therapeutic Chemical (ATC) classification. Sunitinib interacts with CYP3A4 inducers or inhibitors and with P-glycoprotein and ABCG2 substrates. Pharmacodynamic interactions with drugs have also been found. Current information on drug interactions between sunitinib and other drugs is scarce and most of the times it is difficult to apply to clinical practice. Even so, this difficulty in managing drug interactions should not be a reason to ignore them as they can help to explain intolerances and treatment failures. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. Abuse of prescription drugs.

    Science.gov (United States)

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disabled by personal problems with drugs or alcohol; dated in their knowledge of current pharmacology or therapeutics; or deceived by various patient-initiated fraudulent approaches. Even physicians who do not meet any of these descriptions must guard against contributing to prescription drug abuse through injudicious prescribing, inadequate safeguarding of prescription forms or drug supplies, or acquiescing to the demands or ruses used to obtain drugs for other than medical purposes. PMID:2349801

  11. Antidepressants and platinum drugs.

    Science.gov (United States)

    Engelmann, Brigitte J; Ryan, John J; Farrell, Nicholas P

    2014-01-01

    Antidepressants are frequently prescribed concurrently with anti-cancer drugs and may have synergistic, additive or antagonistic effects. The present work investigated the effect of antidepressants on the cytotoxicity of platinum agents cisplatin, carboplatin and oxaliplatin. The cytotoxicity of platinum drugs alone or in combination with antidepressants was measured in HCT116 wild-type (wt), HCT116 (p53 -/-), HT-29, SKOV3 and A2780 cells using an apoptosis-based assay. The effect of antidepressants on platinum cytotoxicity is both cell type- and drug dependent. Mostly additive effects were observed. Desipramine and fluoxetine caused the greatest effects, with cisplatin in general being most sensitive to their presence. There is little effect of p53 status on the drug-drug interaction while the calmodulin inhibitor W7 augmented cisplatin cytotoxicity relative to carboplatin and oxaliplatin. The drug-drug interaction between antidepressants and platinum anti-cancer agents requires detailed evaluation for optimization of patient care.

  12. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user. Based on anecdotal evidence, most people “party” during extended time away from the work environment. Therefore, the following scenarios were envisioned: (1) a person uses an illicit drug at a party on Saturday night (infrequent user); (2) a person uses a drug one time on Friday night and once again on Saturday night (infrequent user); and (3) a person uses a drug on Friday night, uses a drug twice on Saturday night, and once again on Sunday (frequent user).

  13. [Current problems in assessing drug prices].

    Science.gov (United States)

    Lucioni, C

    1989-01-01

    Two reasons provide historical justification for controlling drug prices: safeguarding the consumer and safeguarding public demand. Due to the increased presence of the "third payer" in public health systems this second reason has become more important. Nevertheless, over the last decade, a third purpose has attached to public control of prices: promotion of drug manufacturers economic development. The justification offered for this is that development of pharmaceutical companies contributes to the economic growth of the host country by creating employment, exports and research activity. The situations in Germany, Great Britain and United States are often cited in support of this thesis. As a model for price policy in Italy, however, it has not been successful. The rapid growth of prices in fact has not created greater employment and the foreign exchange deficit has risen rapidly. In other words the growing cost of drugs to the National Health Service has not produced hoped-for economic benefits. It would therefore be opportune to modify the mechanisms of price control by seeking a better balance in the interests involved (safeguarding public demand versus manufacturers economic growth). Methodologies available point to the evaluation of the therapeutic utility of a drug as a useful tool for this purpose. By this method the price of a new drug may only be higher than that of a drug already on the market if its therapeutic utility (which does not coincide only with clinical effectiveness) is greater. Appropriate evaluation techniques of benefits deriving from a new drug (cost-effectiveness and cost-utility) do exist and can be taken into consideration in a new method of calculating drug price.

  14. Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

    DEFF Research Database (Denmark)

    Pudasaini, Nawin; Upadhyay, Pratik Pankaj; Parker, Christian Richard

    2017-01-01

    Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability...... and tabletability, creating significant processability difficulties on a production scale. However, such a habit can be adapted to the needs of downstream processing. To this end, we modified the needle-like crystal habit of the model API 5-aminosalicylic acid (5-ASA). This study reports processability assessment...

  15. Inter-Rater Reliability of the Modified Ashworth Scale and Modified Modified Ashworth Scale in Assessing Poststroke Elbow Flexor Spasticity

    Science.gov (United States)

    Kaya, Taciser; Goksel Karatepe, Altinay; Gunaydin, Rezzan; Koc, Aysegul; Altundal Ercan, Ulku

    2011-01-01

    The Modified Ashworth Scale (MAS) is commonly used in clinical practice for grading spasticity. However, it was modified recently by omitting grade "1+" of the MAS and redefining grade "2". The aim of this study was to investigate the inter-rater reliability of MAS and modified MAS (MMAS) for the assessment of poststroke elbow flexor spasticity.…

  16. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Priya Bawa

    2011-12-01

    Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  17. Observational tests of modified gravity

    International Nuclear Information System (INIS)

    Jain, Bhuvnesh; Zhang Pengjie

    2008-01-01

    Modifications of general relativity provide an alternative explanation to dark energy for the observed acceleration of the Universe. Modified gravity theories have richer observational consequences for large-scale structures than conventional dark energy models, in that different observables are not described by a single growth factor even in the linear regime. We examine the relationships between perturbations in the metric potentials, density and velocity fields, and discuss strategies for measuring them using gravitational lensing, galaxy cluster abundances, galaxy clustering/dynamics, and the integrated Sachs-Wolfe effect. We show how a broad class of gravity theories can be tested by combining these probes. A robust way to interpret observations is by constraining two key functions: the ratio of the two metric potentials, and the ratio of the gravitational 'constant' in the Poisson equation to Newton's constant. We also discuss quasilinear effects that carry signatures of gravity, such as through induced three-point correlations. Clustering of dark energy can mimic features of modified gravity theories and thus confuse the search for distinct signatures of such theories. It can produce pressure perturbations and anisotropic stresses, which break the equality between the two metric potentials even in general relativity. With these two extra degrees of freedom, can a clustered dark energy model mimic modified gravity models in all observational tests? We show with specific examples that observational constraints on both the metric potentials and density perturbations can in principle distinguish modifications of gravity from dark energy models. We compare our result with other recent studies that have slightly different assumptions (and apparently contradictory conclusions).

  18. Cosmological tests of modified gravity.

    Science.gov (United States)

    Koyama, Kazuya

    2016-04-01

    We review recent progress in the construction of modified gravity models as alternatives to dark energy as well as the development of cosmological tests of gravity. Einstein's theory of general relativity (GR) has been tested accurately within the local universe i.e. the Solar System, but this leaves the possibility open that it is not a good description of gravity at the largest scales in the Universe. This being said, the standard model of cosmology assumes GR on all scales. In 1998, astronomers made the surprising discovery that the expansion of the Universe is accelerating, not slowing down. This late-time acceleration of the Universe has become the most challenging problem in theoretical physics. Within the framework of GR, the acceleration would originate from an unknown dark energy. Alternatively, it could be that there is no dark energy and GR itself is in error on cosmological scales. In this review, we first give an overview of recent developments in modified gravity theories including f(R) gravity, braneworld gravity, Horndeski theory and massive/bigravity theory. We then focus on common properties these models share, such as screening mechanisms they use to evade the stringent Solar System tests. Once armed with a theoretical knowledge of modified gravity models, we move on to discuss how we can test modifications of gravity on cosmological scales. We present tests of gravity using linear cosmological perturbations and review the latest constraints on deviations from the standard [Formula: see text]CDM model. Since screening mechanisms leave distinct signatures in the non-linear structure formation, we also review novel astrophysical tests of gravity using clusters, dwarf galaxies and stars. The last decade has seen a number of new constraints placed on gravity from astrophysical to cosmological scales. Thanks to on-going and future surveys, cosmological tests of gravity will enjoy another, possibly even more, exciting ten years.

  19. Bonferroni's and Sidak's modified tests

    Directory of Open Access Journals (Sweden)

    Conagin Armando

    2006-01-01

    Full Text Available Results of practical importance had been discarded testing formulated hypothesis with the aid of statistical analysis of experimental data because of the power of the utilized test. This study compares the power of two Bonferroni's Modified and one Sidak's Modified tests with known tests analyzing 1200 simulated experiments. All differences of means were obtained in relation to the mean of the adopted control to guarantee parametrical magnitude of mean differences. Student's test (type I comparisonwise error and Waller-Duncan's (Bayesian error showed the highest percentage of significative differences, followed by Duncan's, BM2, SiM, BM1, DunnettU's, SiN, BN, Dunnettu's, SNK's, REGWF's, REGWQ's, Tukey's, Sidak's and Bonferroni's tests. For differences equal to zero, Student's and Waller-Duncan's test exhibit 5% frequency of rejection of the null hypothesis, in accordance the nominal error I adopted (alpha = 0.05. All other tests had values below 0.05, generally ranging on 0.01 to 0.02 or less. Depending of the number of zero differences and considering the type I experimentwise error I, Student's, Waller-Duncan's and Duncan's tests showed crescent values of errors (> 0.05, proportional to the number of null differences included in the experiment; all other tests exhibit showed of type I experimentwise error < 0.05, most nearing 0.01-0.02 or less. Efficiency of the three "Modified Tests" was close to DunnettU's test, but higher than the other testes of type I experimentwise error nature (MEER.

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: Drug Use and Viral Infections : Describes how people who engage in drug use or high-risk behaviors associated with drug use also put ...