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Sample records for evaluate local drug

  1. Evaluation of stability and size distribution of sunflower oil-coated micro bubbles for localized drug delivery.

    Science.gov (United States)

    Filho, Walter Duarte de Araujo; Schneider, Fábio Kurt; Morales, Rigoberto E M

    2012-09-20

    Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, thus improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers in localized delivery. In micro fluidics devices for generation of micro bubbles, the bubbles are formed at interface of liquid gas through a strangulation process. A device that uses these features can produce micro bubbles with small size dispersion in a single step. A T-junction micro fluidic device constructed using 3D prototyping was made for the production of mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid layer. Stability studies for micro bubbles with diameters different generated from a liquid phase of the same viscosity were conducted to evaluate whether micro bubbles can be used as drug carriers. The biocompatibility of coating layer, the ability to withstand environmental pressure variations combined with echogenicity, are key factors that they can safely play the role of drug transporters. The normal distribution curve with small dispersion of the diameter of bubbles validates the process of generating micro bubbles with low value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the feasibility of using sunflower oil as the lipid matrix with stable population of bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 μm and 121 minutes for micro bubbles with an average diameter of 73.74 μm, considering bubbles with air as gaseous phase. The results indicate that the micro fluidic device designed can be used for producing micro bubbles with low variation coefficient using sunflower oil as a coating of micro bubbles. These carriers were stable for periods of time that are long enough for clinical applications even when regular air is used as the gas phase. Improved

  2. Evaluation of stability and size distribution of sunflower oil-coated micro bubbles for localized drug delivery

    Directory of Open Access Journals (Sweden)

    Filho WalterDuartedeAraujo

    2012-09-01

    Full Text Available Abstract Background Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, thus improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers in localized delivery. In micro fluidics devices for generation of micro bubbles, the bubbles are formed at interface of liquid gas through a strangulation process. A device that uses these features can produce micro bubbles with small size dispersion in a single step. Methods A T-junction micro fluidic device constructed using 3D prototyping was made for the production of mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid layer. Stability studies for micro bubbles with diameters different generated from a liquid phase of the same viscosity were conducted to evaluate whether micro bubbles can be used as drug carriers. The biocompatibility of coating layer, the ability to withstand environmental pressure variations combined with echogenicity, are key factors that they can safely play the role of drug transporters. Results The normal distribution curve with small dispersion of the diameter of bubbles validates the process of generating micro bubbles with low value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the feasibility of using sunflower oil as the lipid matrix with stable population of bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 μm and 121 minutes for micro bubbles with an average diameter of 73.74 μm, considering bubbles with air as gaseous phase. Conclusion The results indicate that the micro fluidic device designed can be used for producing micro bubbles with low variation coefficient using sunflower oil as a coating of micro bubbles. These carriers were stable for periods of time that are long enough for clinical

  3. Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

    Science.gov (United States)

    Kirtane, Ameya R; Rothenberger, Meghan K; Frieberg, Abby; Nephew, Karla; Schultz-Darken, Nancy; Schmidt, Thomas; Reimann, Thomas; Haase, Ashley T; Panyam, Jayanth

    2017-07-01

    The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report

    Directory of Open Access Journals (Sweden)

    Patricia Miranda Romero

    2015-02-01

    Full Text Available Trastuzumab emtansina (T-DM1 is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC, who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS and the overall survival (OS. It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 €. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at € 70,490,850. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients

  5. A systematic review of economic evaluations of local authority commissioned preventative public health interventions in overweight and obesity, physical inactivity, alcohol and illicit drugs use and smoking cessation in the United Kingdom.

    Science.gov (United States)

    White, Pam; Skirrow, Helen; George, Abraham; Memon, Anjum

    2018-02-16

    Since 2013, local authorities in England have been responsible for commissioning preventative public health interventions. The aim of this systematic review was to support commissioning by collating published data on economic evaluations and modelling of local authority commissioned public health preventative interventions in the UK. Following the PRISMA protocol, we searched for economic evaluations of preventative intervention studies in four different areas: overweight and obesity, physical inactivity, alcohol and illicit drugs use and smoking cessation. The systematic review identified studies between January 1994 and February 2015, using five databases. We synthesized the studies to identify the key methods and examined results of the economic evaluations. The majority of the evaluations related to cost-effectiveness, rather than cost-benefit analyses or cost-utility analyses. These analyses found preventative interventions to be cost effective, though the context of the interventions differed between the studies. Preventative public health interventions in general are cost-effective. There is a need for further studies to support justification of continued and/or increased funding for public health interventions. There is much variation between the types of economically evaluated preventative interventions in our review. Broader studies incorporating different contexts may help support funding for local authority-sponsored public health initiatives.

  6. Evaluation of drug-drug interactions among patients with chronic ...

    African Journals Online (AJOL)

    Introduction: The risk of drug-drug interactions (DDIs) is high in patients with chronic kidney disease (CKD) necessitating dose adjustments or the avoidance of drug combinations. This study aimed to evaluate DDIs among patients with CKD in the University of Nigeria Teaching Hospital (UNTH), Enugu, South-East Nigeria.

  7. Center for Drug Evaluation and Research

    Data.gov (United States)

    Federal Laboratory Consortium — The Center for Drug Evaluation and Research(CDER) performs an essential public health task by making sure that safe and effective drugs are available to improve the...

  8. Evaluation of radiation doses from radioactive drugs

    International Nuclear Information System (INIS)

    Halperin, J.A.; Grove, G.R.

    1977-01-01

    Radioactive new drugs are regulated by the Food and Drug Administration (FDA) in the United States. Before a new drug can be marketed it must have an approved New Drug Application (NDA). Clinical investigations of a radioactive new drug are carried out under a Notice of Claimed Investigational Exemption for a New Drug (IND), submitted to the FDA. In the review of the IND, radiation doses are projected on the basis of experimental data from animal models and from calculations based upon radiation characteristics, predicted biodistribution of the drug in humans, and activity to be administered. FDA physicians review anticipated doses and prevent clinical investigations in humans when the potential risk of the use of a radioactive substance outweighs the prospect of achieving beneficial results from the administration of the drug. In the evaluation of an NDA, FDA staff attempt to assure that the intended diagnostic or therapeutic effect is achievable with the lowest practicable radiation dose. Radiation doses from radioactive new drugs are evaluated by physicians within the FDA. Important radioactive new drugs are also evaluated by the Radiopharmaceuticals Advisory Committee. FDA also supports the Center for Internal Radiation Dosimetry at Oak Ridge, to provide information regarding in vivo distribution and dosimetry to critical organs and the whole body from radioactive new drugs. The process for evaluation of radiation doses from radioactive new drugs for protection against use of unnecessary radiation exposure by patients in nuclear medicine procedures, a

  9. Drug Trafficking Organizations and Local Economic Activity in Mexico.

    Science.gov (United States)

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000-2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations.

  10. Autoradiographic localization of drug and neurotransmitter receptors in the brain

    International Nuclear Information System (INIS)

    Kuhar, M.J.

    1981-01-01

    By combining and adapting various methodologies, it is possible to develop radiohistochemical methods for the light microscopic localization of drug and neurotransmitter receptors in the brain. These methods are valuable complements to other histochemical methods for mapping neurotransmitters; they provide a unique view of neuroanatomy and they can be used to provide valuable new hypotheses about how drugs produce various effects. Interesting 'hot spots' of receptor localizations have been observed in some sensory and limbic areas of the brain. Because most available methods are light microscopic, the development of ultrastructural methods will be a necessary and important extension of this field. (Auth.)

  11. Evaluation of drug interaction microcomputer software: Dambro's Drug Interactions.

    Science.gov (United States)

    Poirier, T I; Giudici, R A

    1990-01-01

    Dambro's Drug Interactions was evaluated using general and specific criteria. The installation process, ease of learning and use were rated excellent. The user documentation and quality of the technical support were good. The scope of coverage, clinical documentation, frequency of updates, and overall clinical performance were fair. The primary advantages of the program are the quick searching and detection of drug interactions, and the attempt to provide useful interaction data, i.e., significance and reference. The disadvantages are the lack of current drug interaction information, outdated references, lack of evaluative drug interaction information, and the inability to save or print patient profiles. The program is not a good value for the pharmacist but has limited use as a quick screening tool.

  12. Performance evaluation of local colour invariants

    NARCIS (Netherlands)

    Burghouts, G.J.; Geusebroek, J.M.

    2009-01-01

    In this paper, we compare local colour descriptors to grey-value descriptors. We adopt the evaluation framework of Mikolayzcyk and Schmid. We modify the framework in several ways. We decompose the evaluation framework to the level of local grey-value invariants on which common region descriptors are

  13. Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

    Directory of Open Access Journals (Sweden)

    Toril Andersen

    2015-01-01

    Full Text Available Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.

  14. Local drug delivery - the early Berlin experience: single drug administration versus sustained release.

    Science.gov (United States)

    Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena

    2011-05-01

    Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.

  15. Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery

    Directory of Open Access Journals (Sweden)

    Sreeja C Nair

    2012-01-01

    Full Text Available Periodontal pockets act as a natural reservoir filled with gingival crevicular fluid for the controlled release delivery of antimicrobials directly. This article reflects the present status of nonsurgical controlled local intrapocket delivery of antimicrobials in the treatment of periodontitis. These sites have specialty in terms of anatomy, permeability, and their ability to retain a delivery system for a desired length of time. A number of antimicrobial products and the composition of the delivery systems, its use, clinical results, and their release are summarized. The goal in using an intrapocket device for the delivery of an antimicrobial agent is the achievement and maintenance of therapeutic drug concentration for the desired period of time. Novel controlled drug delivery system are capable of improving patient compliance as well as therapeutic efficacy with precise control of the rate by which a particular drug dosage is released from a delivery system without the need for frequent administration. These are considered superior drug delivery system because of low cost, greater stability, non-toxicity, biocompatibility, non-immunogenicity, and are biodegradable in nature. This review also focus on the importance and ideal features of periodontal pockets as a drug delivery platform for designing a suitable dosage form along with its potential advantage and limitations. The microbes in the periodontal pocket could destroy periodontal tissues, and a complete knowledge of these as well as an ideal treatment strategy could be helpful in treating this disease.

  16. Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

    Science.gov (United States)

    Zhou, Qiu-Lan; Chen, Zhi-Yi; Yang, Feng

    2014-01-01

    With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers. PMID:25202710

  17. Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

    Directory of Open Access Journals (Sweden)

    Qiu-Lan Zhou

    2014-01-01

    Full Text Available With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo, including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

  18. Spatiotemporal Quantification of Local Drug Delivery Using MRI

    Science.gov (United States)

    Giers, Morgan B.; McLaren, Alex C.; Plasencia, Jonathan D.; McLemore, Ryan; Caplan, Michael R.

    2013-01-01

    Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery was performed to visualize and quantify the time resolved distribution of MRI contrast agents. Three-dimensional T 1 maps (generated from T 1-weighted images with varied T R) were processed using noise-reducing filtering. A segmented region of contrast, from a thresholded image, was converted to concentration maps using the equation 1/T 1 = 1/T 1,0 + R 1 C, where T 1,0 and T 1 are the precontrast and postcontrast T 1 map values, respectively. In this technique, a uniform estimated value for T 1,0 was used. Error estimations were performed for each step. The practical usefulness of this method was assessed using comparisons between devices located in different locations both with and without contrast. The method using a uniform T 1,0, requiring no registration of pre- and postcontrast image volumes, was compared to a method using either affine or deformation registrations. PMID:23710248

  19. Spatiotemporal Quantification of Local Drug Delivery Using MRI

    Directory of Open Access Journals (Sweden)

    Morgan B. Giers

    2013-01-01

    Full Text Available Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI of local drug delivery was performed to visualize and quantify the time resolved distribution of MRI contrast agents. Three-dimensional maps (generated from -weighted images with varied were processed using noise-reducing filtering. A segmented region of contrast, from a thresholded image, was converted to concentration maps using the equation , where and are the precontrast and postcontrast map values, respectively. In this technique, a uniform estimated value for was used. Error estimations were performed for each step. The practical usefulness of this method was assessed using comparisons between devices located in different locations both with and without contrast. The method using a uniform , requiring no registration of pre- and postcontrast image volumes, was compared to a method using either affine or deformation registrations.

  20. Peer Evaluation Can Reliably Measure Local Knowledge

    Science.gov (United States)

    Reyes-García, Victoria; Díaz-Reviriego, Isabel; Duda, Romain; Fernández-Llamazares, Álvaro; Gallois, Sandrine; Guèze, Maximilien; Napitupulu, Lucentezza; Pyhälä, Aili

    2016-01-01

    We assess the consistency of measures of individual local ecological knowledge obtained through peer evaluation against three standard measures: identification tasks, structured questionnaires, and self-reported skills questionnaires. We collected ethnographic information among the Baka (Congo), the Punan (Borneo), and the Tsimane' (Amazon) to…

  1. Evaluation of mesotherapy as a transdermal drug delivery tool.

    Science.gov (United States)

    Kim, S; Kye, J; Lee, M; Park, B

    2016-05-01

    There has been no research about the exact mechanism of transdermal drug delivery during mesotherapy. We aimed to evaluate whether the commercial mesogun can be an appropriate technique for a transdermal drug delivery. We injected blue ink into the polyurethane foam or pig skin with three types of mesotherapy using a commercial mesogun, or local made intradermal injector, or a manual injection of syringe. To assess the internal pressure of the cylinder and drug delivery time, we designed the evaluation setup using a needle tip pressure transducer. All types of injectors induced adequate penetration of blue ink into the polyurethane foam without backflow. In the pig skin, blue ink leaked out rapidly with the backward movement of the needle in the commercial mesogun in contrast to the local made injector or the manual injection of syringe. When the time for backward movement of the syringe approaches 1000 ms, the cylinder pressure of the syringe is saturated at around 25 mmHg which can be translated into the dermal pressure of the pig skin. There should be sufficient time between the insertion and withdrawal of the needle of injector for the adequate transdermal drug delivery and it must be considered for mesotherapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Evaluation of local drug-delivery system containing 2% whole turmeric gel used as an adjunct to scaling and root planing in chronic periodontitis: A clinical and microbiological study

    Directory of Open Access Journals (Sweden)

    Roobal Behal

    2011-01-01

    Full Text Available Aim: To compare the effect of experimental local-drug delivery system containing 2% whole turmeric (gel form as an adjunct to scaling and root planing (SRP with the effect achieved using SRP alone by assessing their respective effects on plaque, gingival inflammation, bleeding on probing pocket depth, relative attachment levels and trypsin-like enzyme activity of "red complex " microorganisms, namely, Bacteroides forsythus, Porphvromonas gingivalis and Treponema denticola. Material and Methods: Thirty subjects with chronic localized or generalized periodontitis with pocket depth of 5 to 7 mm were selected in a split-mouth study design. Control sites received SRP alone, while experimental sites received SRP plus experimental material (2% whole turmeric gel. Plaque index (PI, gingival index (GI, sulcus bleeding index (SBI, probing pocket depth (PPD, relative attachment loss (RAL, microbiological study of collected plaque sample for trypsin-like activity of "red complex" by BAPNA assay were the parameters recorded on day 0, 30 days and 45 days. Results: Both groups demonstrated statistically significant reduction in PI, GI, SBI, PPD; and gain in RAL. Significant reduction in the trypsin-like enzyme activity of "red complex" (BAPNA values was observed for both the groups when compared to the baseline activity. Greater reduction was seen in all the parameters in the experimental group in comparison to the control group. Conclusion: The experimental local drug-delivery system containing 2% whole turmeric gel can be effectively used as an adjunct to scaling and root planing and is more effective than scaling and root planing alone in the treatment of periodontal pockets.

  3. Preoperative evaluation of locally spreaded pelvic tumors

    International Nuclear Information System (INIS)

    Baramia, M.; Todua, F.; Gotsadze, D.; Khutulashvili, N.; Lashkhi, K.; Nadareishvili, A.

    1998-01-01

    Am of the study: preoperative evaluation of patients with locally advanced pelvic tumors subjected to pelvic exenteration. Determine operability to avoid explorative laparatomies, which cause serious complications in these patients. Evaluate condition of urinary system in case of this pathology. Materials and methods: 34 patients with locally advanced pelvic tumors where pelvic exenteration was attempted were studied. Along with other methods of diagnostic CT and MRI were performed. Results: In all patients secondary involvement of the urinary bladder was noted. In 30 patients CT and MR findings were confirmed (88,2%) intraoperatively and different types of pelvic organs exenteration were performed. In 1 case spread of tomoruos infiltrate to the pelvic wall and common iliac vessels was detected intraoperatively (patient had history of radiation therapy). In 2 cases carcinomatosis of the peritoneum was found. In 1 case involvement of urinary bladder was simulated by close attachment of enlarged uterus. Conclusion: Obtained results show, that CT and MR are highly informative methods of disease spread evaluation and thus determining operability. Radiotherapy performed prior to operation sets difficulties in differentiation for tumourous infiltrate and post-radiotherapy changes in pelvis. (Full text)

  4. Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes.

    Science.gov (United States)

    Arai, Takao; Benny, Ofra; Joki, Tatsuhiro; Menon, Lata G; Machluf, Marcelle; Abe, Toshiaki; Carroll, Rona S; Black, Peter M

    2010-04-01

    The purpose of our study was to evaluate the application of thermoreversible gelation polymer (TGP) as a local drug delivery system for malignant glioma. Polymeric microspheres or liposomes loaded with doxorubicin (sphere-dox or lipo-dox) were combined with TGP to provide continuous drug delivery of doxorubicin (dox) for kinetic release studies and cell viability assays on glioma cell lines in vitro. For in vivo studies, TGP loaded with dox alone (TGP-dox) was combined with sphere-dox or lipo-dox. Their antitumor effects on subcutaneous human glioma xenografts were evaluated in nude mice. In vitro, TGP combined with sphere-dox or lipo-dox released dox for up to 30 days. In vivo, TGP-dox combined with sphere-dox or lipo-dox inhibited subcutaneous glioma tumor growth until day 32 and day 38, respectively. TGP in combination with microspheres or liposomes successfully prolonged the release of dox and its antitumor effects.

  5. Magnetically induced localized on-demand drug delivery

    NARCIS (Netherlands)

    Rovers, S.A.

    2010-01-01

    Externally triggered on-demand drug release from an implant can significantly improve the efficiency of the drug therapy since it enables the patient or physician to control the dosing to the patient’s needs and releases the drug only at the required location in the human body. Therefore, patient

  6. Evaluation of superoxide dismutase levels in local drug delivery system containing 0.2% curcumin strip as an adjunct to scaling and root planing in chronic periodontitis: A clinical and biochemical study

    Directory of Open Access Journals (Sweden)

    Sugumari Elavarasu

    2016-01-01

    Full Text Available Aim: Curcumin has proven properties such as anti-inflammatory, antioxidant, antimicrobial, and it also accelerates wound healing. The purpose of this study was to investigate the level of superoxide dismutase (SOD enzyme, in gingival crevicular fluid (GCF, and the impact of nonsurgical treatment on the antioxidant profile using 0.2% curcumin strip as local drug delivery. Materials and Methods: A total of twenty subjects of age 35–55 years and 15 subjects with chronic periodontitis, each with bilateral 5–6 mm probing pocket depth, were selected for this study. Healthy group consists of 5 sites in which no bleeding on probing, no pocket depth. Group I – It consists of 15 sites with chronic periodontitis, in which scaling and root planing (SRP was done (control group. Group II – It consists of 15 sites, in which SRP followed by the placement of curcumin strip inside the pocket (SRP + curcumin strip (test group. GCF collection was done preoperatively and postoperatively after 21 days. The SOD activity was assessed using enzyme-linked immunosorbent assay. Results: In this study, all the clinical parameters were significantly reduced in test and control sites. Further, SOD levels were significantly improved in test sites when compared with control sites. Conclusion: Thus, the present study concluded that curcumin strip can be effectively used as an adjunct to SRP in treatment of chronic periodontitis and serves as antioxidant in subgingival environment.

  7. Systematic evaluation of drug-disease relationships to identify leads for novel drug uses.

    Science.gov (United States)

    Chiang, A P; Butte, A J

    2009-11-01

    Drug repositioning refers to the discovery of alternative uses for drugs--uses that are different from that for which the drugs were originally intended. One challenge in this effort lies in choosing the indication for which a drug of interest could be prospectively tested. We systematically evaluated a drug treatment-based view of diseases in order to address this challenge. Suggestions for novel drug uses were generated using a "guilt by association" approach. When compared with a control group of drug uses, the suggested novel drug uses generated by this approach were significantly enriched with respect to previous and ongoing clinical trials.

  8. Evaluation of Drug Quality (III): Determination of Ciprofloxacin ...

    African Journals Online (AJOL)

    user

    Evaluation of Drug Quality (III): Determination of Ciprofloxacin Hydrochloride ... two methods were interpreted in terms of differences in sensitivities of the methods. It was ..... Agency for Food, Drug Administration and. Control ... regulatory standards and specified identity. Therefore drug analysis requires that drugs meet their.

  9. Hospital pharmacists' evaluation of drug wholesaler services.

    Science.gov (United States)

    Allen, W O; Ryan, M R; Roberts, K B

    1983-10-01

    Services provided by drug wholesalers were evaluated by hospital pharmacists. A survey was mailed to 1500 randomly selected pharmacy directors. Respondents indicated availability and use of 26 customer services. Pharmacists rated the services that they used on the basis of importance of the service and satisfaction with the service. The 644 returned questionnaires indicated that most services were available to a large majority of respondents. Most services used were rated as important or essential. Most respondents were satisfied with wholesaler services; the service with which the most respondents were dissatisfied was stocking of pharmaceuticals in single-unit packaging. Of other services that were widely used and rated important, prompt crediting for delivery errors, few out-of-stock items, frequent pickup of return merchandise, and stocking of injectable pharmaceuticals received low satisfaction ratings. Same-day delivery service and emergency delivery of prescription items were unavailable to more than 40% of respondents. Hospital pharmacists were generally satisfied with services provided by drug wholesalers. Wholesalers should be aware of the particular service needs of hospital pharmacists, and further studies of these needs should be conducted.

  10. [Evaluation of two closed-system drug transfer device in the antineoplastic drug elaboration process].

    Science.gov (United States)

    Gómez-Álvarez, Sandra; Porta-Oltra, Begoña; Hernandez-Griso, Marta; Pérez-Labaña, Francisca; Climente-Martí, Mónica

    2016-01-01

    to assess the impact of two closed-system drug transfer device on the local and environmental contamination and preparation times in the process of preparation of parenteral chemotherapy compared to the standard system. prospective observational study. Two different closed- systems providers, Care Fusion® and Icu Medical®, were compared to standard preparation. 15 nurses of Pharmacy Department prepared 5 preparations each one, one with the standard procedure and four using closed-systems. To evaluate the contamination, a fluorescein solution 0.5% was prepared. Two kind of contamination were evaluated, local (three points connection: closed-system connect vial, syringe and final infusion bags) and environmental (gloves and countertop). Percentage of contaminated preparations was obtained in each one. Time taken by each nurse in each preparation was recorded. 75 preparations were prepared. Local contamination was reduced 21% and 75% in closed-system Icu Medical® and Care Fusion® respectively. Care Fusion® closed system, local contamination was significantly lower than the standard system to the vial, syringe and final package, while Icu Medical® closed-systems only was significantly lower in the connection to the vial. Time of preparation was increased significantly with the use of closed-system between 23.4 and 30.5 seconds. both closed-systems drug transfer device have shown an improvement in contamination than the use of the standard system. However, preparation time has been significantly increased with the use of both systems. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  11. 76 FR 45268 - Center for Drug Evaluation and Research, Approach to Addressing Drug Shortage; Public Workshop

    Science.gov (United States)

    2011-07-28

    ...] Center for Drug Evaluation and Research, Approach to Addressing Drug Shortage; Public Workshop AGENCY... Administration (FDA) is announcing a public workshop regarding the approach of the Center for Drug Evaluation and..., and to gain additional insight from, professional societies, patient advocates, industry, consumer...

  12. Postmenopausal vaginal atrophy: evaluation of treatment with local estrogen therapy

    Directory of Open Access Journals (Sweden)

    Minkin MJ

    2014-03-01

    Full Text Available Mary Jane Minkin,1 Ricardo Maamari,2 Suzanne Reiter3 1Department of Gynecology and Reproductive Medicine, Yale University School of Medicine, New Haven, CT, USA; 2Novo Nordisk Inc., Plainsboro, NJ, USA; 3Mid-County Health Center, Largo, FL, USA Abstract: Postmenopausal vaginal atrophy, resulting from decreased estrogen production, frequently requires treatment. Estrogen preparations provide the most effective treatment; local application is preferred to systemic drugs when treating only vaginal symptoms. As local estrogen therapies have comparable efficacy, this study aimed to understand treatment practices, assess experiences with different forms of local estrogen-delivering applicators, and evaluate satisfaction. Women who were US residents aged ≥18 years, menopausal (no spontaneous menstrual period for ≥1 year or with a double oophorectomy, and receiving local estrogen therapy for 1–6 months (vaginal cream [supplied with a reusable applicator] or vaginal tablets [supplied with a single-use/disposable applicator], completed an online questionnaire. Data from 200 women (100 cream users and 100 tablet users; mean therapy duration 3.48 months showed that most stored medication in the room in which it was applied (88% and applied it at bedtime (71%, a procedure for which cream users required, on average, more than twice the time of tablet users (5.08 minutes versus 2.48 minutes. Many cream users applied larger-than-prescribed amounts of cream, attempting to achieve greater efficacy (42%, or lower-than-recommended doses (45%, most frequently to avoid messiness (33% or leakage (30%. More tablet users (69% than cream users (14% were "extremely satisfied" with their applicator. Postmenopausal women using local estrogen therapy were generally more satisfied with the application of vaginal tablets than cream. Patient satisfaction may help to facilitate accurate dosing. Positive perceptions of medication will help to optimize treatment, which

  13. Ultrasound-triggered local release of lipophilic drugs from a novel polymeric ultrasound contrast agent

    NARCIS (Netherlands)

    Kooiman, K.; Böhmer, M.R.; Emmer, M.; Vos, Hendrik J.; Chlon, C.; Foppen-Harteveld, M.; Versluis, Michel; de Jong, N.; van Wamel, A.; Hennink, W.E.; Feijen, J.; Sam, A.P.

    2008-01-01

    The advantage of ultrasound contrast agents (UCAs) as drug delivery systems is the ability to non-invasively control the local and triggered release of a drug or gene. In this study we designed and characterized a novel UCA-based drug delivery system, based on polymer-shelled microcapsules filled

  14. Approved Drug Products with Therapuetic Equivalence Evaluations (Orange Book)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The publication Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book) identifies drug products approved on...

  15. Evaluation of Information Contained in Drug Advertisement and ...

    African Journals Online (AJOL)

    Evaluation of Information Contained in Drug Advertisement and Promotion Materials in Nigeria. ... Conclusion: This study reveals that advertising materials used in promoting drugs in Nigeria have incomplete ... AJOL African Journals Online.

  16. Localized irradiations, evaluation through 'Comet Assay'

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Taja, Maria R.; Nasazzi, Nora B.; Bustos, N.; Cavalieri, H.; Bolgiani, A.

    2000-01-01

    During the last 50 years various radiation accidents involving localized irradiations occurred, resulting mainly from improper handling of sealed sources of Cobalt 60, Cesium 137 or Iridium 192 at work placed for industrial gammagraphy and other radiation sources. Severe skin reaction may developed at the contact sites. Such inhomogeneous irradiations lead to a differential exposure of lymphocytes in lymphatic tissues or other organs that may recirculate into the peripheral blood producing a mixed irradiated and unirradiated population of lymphocytes. Applying the mathematical models 'Contaminated Poisson' of Dolphin and Qdr method of Sasaki, a mean dose in the irradiated body area and its size can be estimated from unstable chromosome aberration scoring. There are also different biophysical techniques that can give response in localized irradiations. Biological dosimetry is a necessary complement to physical and clinical dosimetries. Thus, there is increasing interest in the assessment of biological markers that permit the detection of radiation induced damage in the localized irradiations. The 'Comet Assay' (single cell gel electrophoresis) is a sensitive, rapid and relatively inexpensive method for measuring DNA damage in individual cells. Single cells are embedded in agarose on microscope slides, lysed to remove the majority of the proteins, electrophoresed, then stained with ethidium bromide in order to visualize the DNA. When visualized using a fluorescent microscope, DNA of undamaged cells appears as a spherical mass occupying the cavity formed by the lysed cell. Following radiation damage, the smaller the fragment size and the grater the number of fragments of DNA, the grater the percentage of DNA that it is able to migrate in an electric field, forming a comet image. The assay can be performed under alkaline conditions to examine DNA single strand breaks (SSBs), or in non denaturing (neutral) conditions to measure double strand breaks (DSBs) in individual

  17. Evaluation of wireless Local Area Networks

    Science.gov (United States)

    McBee, Charles L.

    1993-09-01

    This thesis is an in-depth evaluation of the current wireless Local Area Network (LAN) technologies. Wireless LAN's consist of three technologies: they are infrared light, microwave, and spread spectrum. When the first wireless LAN's were introduced, they were unfavorably labeled slow, expensive, and unreliable. The wireless LAN's of today are competitively priced, more secure, easier to install, and provide equal to or greater than the data throughput of unshielded twisted pair cable. Wireless LAN's are best suited for organizations that move office staff frequently, buildings that have historical significance, or buildings that have asbestos. Additionally, an organization may realize a cost savings of between $300 to $1,200 each time a node is moved. Current wireless LAN technologies have a positive effect on LAN standards being developed by the Defense Information System Agency (DISA). DoD as a whole is beginning to focus on wireless LAN's and mobile communications. If system managers want to remain successful, they need to stay abreast of this technology.

  18. Localized irradiations, Evaluation through ''comet assay''

    International Nuclear Information System (INIS)

    Giorgio, M.D.; Taja, M.R.; Nasazzi, N.B.; Bustos, N.; Cavalieri, H.; Bolgiani, A.

    2000-01-01

    During the last 50 years various radiation accidents involving localized irradiations occurred, resulting mainly from improper handling of sealed sources Co 60 , Cs 137 or Ir 192 at workplaces for industrial gammagraphy. Severe skin reaction may develop at the contact sites. Such inhomogeneous irradiations lead to a differential exposure of lymphocytes in lymphatic tissues or other organs that may recirculate into the peripheral blood producing a mixed irradiated and unirradiated population of lymphocytes. Applying the mathematical models ''Contaminated Poisson'' of Dolphin and Qdr method of Sasaki, a mean dose in the irradiated body area and its size can be estimated from unstable chromosome aberration scoring. This give an indication of the proportion of haemopoietic stem cell compartment involved in the overexposure. There are also different biophysical techniques that can give responses in biological dosimetry. The ''Comet Assay'' (single cell gel electrophoresis) is a sensitive and rapid method for DNA strand break detection in individual cells. The advantages of the technique include: collection of data at the level of individual cell; the need for small numbers of cells per sample; its sensitivity for detecting DNA damage and that virtually any eukaryote cell population is amenable to analysis. The objective of this work is to apply ''Comet Assay'' method to evaluate the effect of radiation on skin and subcutaneous tissues, differentiating irradiated from unirradiated body areas. It could provide a useful tool to estimate the extension and the dose in the irradiated region, contributing with the current techniques. In this first study, we evaluate the alkaline comet assay as a method for detection of DNA radiation induced damage in keratinocytes from primary culture obtained from full thickness skin biopsies of patients requiring grafts. Skin and, particularly, keratinocytes were selected as an appropriate cellular system due to: Skin, the first barrier

  19. Development, use and evaluation of drugs

    DEFF Research Database (Denmark)

    Hansen, E H; Launsø, Laila

    1987-01-01

    . Drugs offer a standard solution to health problems independent of the individuals' social life. Thus drugs become a tool which function in agreement with the disintegrated and achievement-orientated approach to disease as it is organized today. In general the statements in this article are not limited...

  20. Swallowable smart pills for local drug delivery: present status and future perspectives.

    Science.gov (United States)

    Goffredo, Rosa; Accoto, Dino; Guglielmelli, Eugenio

    2015-01-01

    Smart pills were originally developed for diagnosis; however, they are increasingly being applied to therapy - more specifically drug delivery. In addition to smart drug delivery systems, current research is also looking into localization systems for reaching the target areas, novel locomotion mechanisms and positioning systems. Focusing on the major application fields of such devices, this article reviews smart pills developed for local drug delivery. The review begins with the analysis of the medical needs and socio-economic benefits associated with the use of such devices and moves onto the discussion of the main implemented technological solutions with special attention given to locomotion systems, drug delivery systems and power supply. Finally, desired technical features of a fully autonomous robotic capsule for local drug delivery are defined and future research trends are highlighted.

  1. Development and Evaluation of Chronotherapeutic Drug Delivery ...

    African Journals Online (AJOL)

    Conclusion: The developed system is capable of releasing the drug after a 4-h lag period. However ... concentration would be at its maximum level, ... spheronizer (Caleva MBS, UK)operating at .... capsules show that the color intensity of the.

  2. Magnetic nanoparticles for local drug delivery using magnetic implants

    International Nuclear Information System (INIS)

    Fernandez-Pacheco, Rodrigo; Marquina, Clara; Gabriel Valdivia, J.

    2007-01-01

    Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of FeC nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields

  3. Magnetic nanoparticles for local drug delivery using magnetic implants

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Pacheco, Rodrigo [Instituto Universitario de Investigacion en Nanociencia de Aragon (INA), Universidad de Zaragoza, Edif. Inter. II, 50009 Zaragoza (Spain); Marquina, Clara [Instituto de Ciencia de Materiales de Aragon (ICMA), CSIC-Universidad de Zaragoza, Facultad de Ciencias, 50009 Zaragoza (Spain); Gabriel Valdivia, J. [Instituto Universitario de Investigacion en Nanociencia de Aragon (INA), Universidad de Zaragoza, Edif. Inter. II, 50009 Zaragoza (Spain); Hospital Clinico Universitario ' Lozano Blesa' , Avda Gomez Laguna, 50009 Zaragoza (Spain)] (and others)

    2007-04-15

    Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of FeC nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields.

  4. Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression

    Directory of Open Access Journals (Sweden)

    Abdullah Mayati

    2017-04-01

    Full Text Available Drug transporters are now recognized as major actors in pharmacokinetics, involved notably in drug–drug interactions and drug adverse effects. Factors that govern their activity, localization and expression are therefore important to consider. In the present review, the implications of protein kinases C (PKCs in transporter regulations are summarized and discussed. Both solute carrier (SLC and ATP-binding cassette (ABC drug transporters can be regulated by PKCs-related signaling pathways. PKCs thus target activity, membrane localization and/or expression level of major influx and efflux drug transporters, in various normal and pathological types of cells and tissues, often in a PKC isoform-specific manner. PKCs are notably implicated in membrane insertion of bile acid transporters in liver and, in this way, are thought to contribute to cholestatic or choleretic effects of endogenous compounds or drugs. The exact clinical relevance of PKCs-related regulation of drug transporters in terms of drug resistance, pharmacokinetics, drug–drug interactions and drug toxicity remains however to be precisely determined. This issue is likely important to consider in the context of the development of new drugs targeting PKCs-mediated signaling pathways, for treating notably cancers, diabetes or psychiatric disorders.

  5. The evaluation of the abuse liability of drugs.

    Science.gov (United States)

    Johanson, C E

    1990-01-01

    In order to place appropriate restrictions upon the availability of certain therapeutic agents to limit their abuse, it is important to assess abuse liability, an important aspect of drug safety evaluation. However, the negative consequences of restriction must also be considered. Drugs most likely to be tested are psychoactive compounds with therapeutic indications similar to known drugs of abuse. Methods include assays of pharmacological profile, drug discrimination procedures, self-administration procedures, and measures of drug-induced toxicity including evaluations of tolerance and physical dependence. Furthermore, the evaluation of toxicity using behavioural end-points is an important component of the assessment, and it is generally believed that the most valid procedure in this evaluation is the measurement of drug self-administration. However, even this method rarely predicts the extent of abuse of a specific drug. Although methods are available which appear to measure relative abuse liability, these procedures are not validated for all drug classes. Thus, additional strategies, including abuse liability studies in humans, modelled after those used with animals, must be used in order to make a more informed prediction. Although there is pressure to place restrictions on new drugs at the time of marketing, in light of the difficulty of predicting relative abuse potential, a better strategy might be to market a drug without restrictions, but require postmarketing surveillance in order to obtain more accurate information on which to base a final decision.

  6. Use of monorail PTCA balloon catheter for local drug delivery.

    Science.gov (United States)

    Trehan, Vijay; Nair, Girish M; Gupta, Mohit D

    2007-01-01

    We report the use of monorail coronary balloon as an infusion catheter to give bailout abciximab selectively into the site of stent thrombosis as an adjunct to plain old balloon angioplasty (POBA) in a patient of subacute stent thrombosis of the left anterior descending coronary artery. The balloon component (polyamide material) of the monorail balloon catheter was shaved off the catheter so that abciximab injected through the balloon port of the catheter exited out the shaft of the balloon catheter at the site from where the balloon material was shaved off. We believe that selective infusion with abciximab along with POBA established antegrade flow and relieved the patient's ischemia. In the absence of essential hardware to give intracoronary drugs in an emergency situation, one may employ our technique of infusion through a monorail balloon catheter after shaving the balloon component from the catheter.

  7. Evaluation of local corrosion life by statistical method

    International Nuclear Information System (INIS)

    Kato, Shunji; Kurosawa, Tatsuo; Takaku, Hiroshi; Kusanagi, Hideo; Hirano, Hideo; Kimura, Hideo; Hide, Koichiro; Kawasaki, Masayuki

    1987-01-01

    In this paper, for the purpose of achievement of life extension of light water reactor, we examined the evaluation of local corrosion by satistical method and its application of nuclear power plant components. There are many evaluation examples of maximum cracking depth of local corrosion by dowbly exponential distribution. This evaluation method has been established. But, it has not been established that we evaluate service lifes of construction materials by satistical method. In order to establish of service life evaluation by satistical method, we must strive to collect local corrosion dates and its analytical researchs. (author)

  8. Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study

    International Nuclear Information System (INIS)

    Lee, Don Haeng; Kang, Sung-Gwon; Jeong, Seok; Yoon, Chang Jin; Choi, Jung-Ah; Byun, Ju Nam; Park, Jae Hyung; Lee, Kyu Back

    2006-01-01

    The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model

  9. Cost Evaluation of Commonly Prescribed Antihypertensive Drugs ...

    African Journals Online (AJOL)

    It was also concluded that generic prescription should be encouraged among prescribers to lessen the financial burden of patients because drugs marketed under generic names are usually cheaper than those with brand names. Key words: Brand, Generic,Prescription, Antihypertensives,Cost. [Nig. Jnl Health & Biomedical ...

  10. Using Respondent-Driven Sampling to Recruit Illegal Drug Purchasers to Evaluate a Drug Market Intervention.

    Science.gov (United States)

    Ober, Allison J; Sussell, Jesse; Kilmer, Beau; Saunders, Jessica; Heckathorn, Douglas D

    2016-04-01

    Violent drug markets are not as prominent as they once were in the United States, but they still exist and are associated with significant crime and lower quality of life. The drug market intervention (DMI) is an innovative strategy that uses focused deterrence, community engagement, and incapacitation to reduce crime and disorder associated with these markets. Although studies show that DMI can reduce crime and overt drug activity, one perspective is prominently missing from these evaluations: those who purchase drugs. This study explores the use of respondent-driven sampling (RDS)-a statistical sampling method-to approximate a representative sample of drug users who purchased drugs in a targeted DMI market to gain insight into the effect of a DMI on market dynamics. Using RDS, we recruited individuals who reported hard drug use (crack or powder cocaine, heroin, methamphetamine, or illicit use of prescriptions opioids) in the last month to participate in a survey. The main survey asked about drug use, drug purchasing, and drug market activity before and after DMI; a secondary survey asked about network characteristics and recruitment. Our sample of 212 respondents met key RDS assumptions, suggesting that the characteristics of our weighted sample approximate the characteristics of the drug user network. The weighted estimates for market purchasers are generally valid for inferences about the aggregate population of customers, but a larger sample size is needed to make stronger inferences about the effects of a DMI on drug market activity. © The Author(s) 2016.

  11. Compulsory patent licensing and local drug manufacturing capacity in Africa

    Science.gov (United States)

    2014-01-01

    Abstract Africa has the highest disease burden in the world and continues to depend on pharmaceutical imports to meet public health needs. As Asian manufacturers of generic medicines begin to operate under a more protectionist intellectual property regime, their ability to manufacture medicines at prices that are affordable to poorer countries is becoming more circumscribed. The Doha Declaration on the TRIPS Agreement and Public Health gives member states of the World Trade Organization (WTO) the right to adopt legislation permitting the use of patented material without authorization by the patent holder, a provision known as “compulsory licensing”. For African countries to take full advantage of compulsory licensing they must develop substantial local manufacturing capacity. Because building manufacturing capacity in each African country is daunting and almost illusory, an African free trade area should be developed to serve as a platform not only for the free movement of goods made pursuant to compulsory licences, but also for an economic or financial collaboration towards the development of strong pharmaceutical manufacturing capacity in the continent. Most countries in Africa are in the United Nations list of least developed countries, and this allows them, under WTO law, to refuse to grant patents for pharmaceuticals until 2021. Thus, there is a compelling need for African countries to collaborate to build strong pharmaceutical manufacturing capacity in the continent now, while the current flexibilities in international intellectual property law offer considerable benefits. PMID:24700981

  12. Evaluation of Drug Utilization Pattern for Patients of Bronchial ...

    African Journals Online (AJOL)

    Evaluation of Drug Utilization Pattern for Patients of Bronchial Asthma in a Government Hospital of Saudi Arabia. ... Background: Bronchial asthma is a social and economic healthcare burden. Drug utilization studies are ... Salbutamol and budesonide were the most common from each group, respectively. 89.5% of the ...

  13. Formulation and Evaluation of Rifampicin Liposomes for Buccal Drug Delivery.

    Science.gov (United States)

    Lankalapalli, Srinivas; Tenneti, V S Vinai Kumar

    2016-01-01

    Drug delivery through liposomes offers several advantages, but still challenging to the researchers for the use of liposomes as carriers in drug delivery due to their poor physical stability, unpredictable drug encapsulation and systemic availability of the loaded drug. The present investigation was planned with an objective to prepare Rifampicin loaded liposomes by using response surface methodology of statistical 32 factorial design and further to formulate them into pastilles for deliver through buccal route thereby to enhance systemic absorption. Rifampicin liposomes were prepared by using different ratios of soya lecithin and cholesterol by solvent Injection method. These liposomes were characterized by using optical microscopy, Scanning Electron Microscopy (SEM) and evaluated for particle size, entrapment efficiency (EE), in vitro and ex vivo drug release. Main effects and interaction terms of the formulation variables were evaluated quantitatively using a mathematical statistical model approach showing that both independent variables have significant (P value value: 0.0273), percentage entrapment efficiency (P value: 0.0096), percentage drug release through dialysis membrane (P value: 0.0047) and percentage drug release through porcine buccal membrane (P value: 0.0019). The statistical factorial design of liposomal formulations fulfilled all the requirements of the target set and exhibited suitable values for the selected test parameters. Pastilles were prepared for liposomes using glycerol gelatin base and were found to be soft, smooth with uniform drug content and drug release.

  14. Local fit evaluation of structural equation models using graphical criteria.

    Science.gov (United States)

    Thoemmes, Felix; Rosseel, Yves; Textor, Johannes

    2018-03-01

    Evaluation of model fit is critically important for every structural equation model (SEM), and sophisticated methods have been developed for this task. Among them are the χ² goodness-of-fit test, decomposition of the χ², derived measures like the popular root mean square error of approximation (RMSEA) or comparative fit index (CFI), or inspection of residuals or modification indices. Many of these methods provide a global approach to model fit evaluation: A single index is computed that quantifies the fit of the entire SEM to the data. In contrast, graphical criteria like d-separation or trek-separation allow derivation of implications that can be used for local fit evaluation, an approach that is hardly ever applied. We provide an overview of local fit evaluation from the viewpoint of SEM practitioners. In the presence of model misfit, local fit evaluation can potentially help in pinpointing where the problem with the model lies. For models that do fit the data, local tests can identify the parts of the model that are corroborated by the data. Local tests can also be conducted before a model is fitted at all, and they can be used even for models that are globally underidentified. We discuss appropriate statistical local tests, and provide applied examples. We also present novel software in R that automates this type of local fit evaluation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  15. EVALUATION OF SIFT AND SURF FOR VISION BASED LOCALIZATION

    Directory of Open Access Journals (Sweden)

    X. Qu

    2016-06-01

    Full Text Available Vision based localization is widely investigated for the autonomous navigation and robotics. One of the basic steps of vision based localization is the extraction of interest points in images that are captured by the embedded camera. In this paper, SIFT and SURF extractors were chosen to evaluate their performance in localization. Four street view image sequences captured by a mobile mapping system, were used for the evaluation and both SIFT and SURF were tested on different image scales. Besides, the impact of the interest point distribution was also studied. We evaluated the performances from for aspects: repeatability, precision, accuracy and runtime. The local bundle adjustment method was applied to refine the pose parameters and the 3D coordinates of tie points. According to the results of our experiments, SIFT was more reliable than SURF. Apart from this, both the accuracy and the efficiency of localization can be improved if the distribution of feature points are well constrained for SIFT.

  16. Prodigiosin release from an implantable biomedical device: kinetics of localized cancer drug release

    Energy Technology Data Exchange (ETDEWEB)

    Danyuo, Y.; Obayemi, J.D.; Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Ani, C.J. [Department of Theoretical Physics, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Odusanya, O.S. [Biotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO), Abuja, Federal Capital Territory (Nigeria); Oni, Y. [Department of Chemistry, Bronx Community College, New York, NY (United States); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY (United States); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Malatesta, K. [Department of Chemistry, Bronx Community College, New York, NY (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering 1 Olden Street, Princeton, NJ 08544 (United States)

    2014-09-01

    This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10{sup −12} m{sup 2}/s and 4.8 × 10{sup −6} m{sup 2}/s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices. - Highlights: • Fabricated thermo-sensitive hydrogels for localized drug release from an implantable biomedical device. • Determined the cancer drug diffusion mechanisms of PNIPA-co-AM copolymer hydrogel. • Encapsulated PNIPA-based hydrogels in PDMS capsules for controlled drug delivery. • Established the kinetics of drug release from gels and channels in an implantable biomedical device. • Demonstrated the potential for the controlled release of prodigiosin (PG) as an anticancer drug.

  17. Prodigiosin release from an implantable biomedical device: kinetics of localized cancer drug release

    International Nuclear Information System (INIS)

    Danyuo, Y.; Obayemi, J.D.; Dozie-Nwachukwu, S.; Ani, C.J.; Odusanya, O.S.; Oni, Y.; Anuku, N.; Malatesta, K.; Soboyejo, W.O.

    2014-01-01

    This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10 −12 m 2 /s and 4.8 × 10 −6 m 2 /s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices. - Highlights: • Fabricated thermo-sensitive hydrogels for localized drug release from an implantable biomedical device. • Determined the cancer drug diffusion mechanisms of PNIPA-co-AM copolymer hydrogel. • Encapsulated PNIPA-based hydrogels in PDMS capsules for controlled drug delivery. • Established the kinetics of drug release from gels and channels in an implantable biomedical device. • Demonstrated the potential for the controlled release of prodigiosin (PG) as an anticancer drug

  18. Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naren Subbiah

    2017-01-01

    Full Text Available Phospholipid-based deformable nanovesicles (DNVs that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol. AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.

  19. Intracranial self-stimulation to evaluate abuse potential of drugs.

    Science.gov (United States)

    Negus, S Stevens; Miller, Laurence L

    2014-07-01

    Intracranial self-stimulation (ICSS) is a behavioral procedure in which operant responding is maintained by pulses of electrical brain stimulation. In research to study abuse-related drug effects, ICSS relies on electrode placements that target the medial forebrain bundle at the level of the lateral hypothalamus, and experimental sessions manipulate frequency or amplitude of stimulation to engender a wide range of baseline response rates or response probabilities. Under these conditions, drug-induced increases in low rates/probabilities of responding maintained by low frequencies/amplitudes of stimulation are interpreted as an abuse-related effect. Conversely, drug-induced decreases in high rates/probabilities of responding maintained by high frequencies/amplitudes of stimulation can be interpreted as an abuse-limiting effect. Overall abuse potential can be inferred from the relative expression of abuse-related and abuse-limiting effects. The sensitivity and selectivity of ICSS to detect abuse potential of many classes of abused drugs is similar to the sensitivity and selectivity of drug self-administration procedures. Moreover, similar to progressive-ratio drug self-administration procedures, ICSS data can be used to rank the relative abuse potential of different drugs. Strengths of ICSS in comparison with drug self-administration include 1) potential for simultaneous evaluation of both abuse-related and abuse-limiting effects, 2) flexibility for use with various routes of drug administration or drug vehicles, 3) utility for studies in drug-naive subjects as well as in subjects with controlled levels of prior drug exposure, and 4) utility for studies of drug time course. Taken together, these considerations suggest that ICSS can make significant contributions to the practice of abuse potential testing. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Evaluating California local land use plan's environmental impact reports

    International Nuclear Information System (INIS)

    Tang Zhenghong; Bright, Elise; Brody, Samuel

    2009-01-01

    Local land use planning has profound impacts on environmental quality; however, few empirical studies have been conducted to systematically measure local land use plans' environmental assessment quality and to identify the factors influencing it. This paper analyzes the quality of 40 Environmental Impact Reports (EIRs) of local jurisdictions' land use plans in California. A plan evaluation protocol defined by five core components and sixty-three indicators is developed to measure the quality of local land use plans' EIRs. The descriptive results indicate that the local jurisdictions produce relatively good quality on its EIRs, but there is still much room for improvement. There are large variations in the quality of EIRs across local jurisdictions. The regression results further highlight three major factors that can significantly influence local land use plan's EIR quality: number of planners, plan updating ability, and development pressure

  1. Role of imaging techniques in the evaluation of cardiovascular drugs

    International Nuclear Information System (INIS)

    Sugishita, Yasuro; Matsuda, Mitsuo; Ajisaka, Ryuichi

    1985-01-01

    In order to investigate the role of imaging in the evaluation of medical treatment in heart diseases, radionuclide angiocardiography, echocardiography and Doppler echocardiography were applied in the cases of various kinds of heart diseases. Acute and chronic effects of antianginal drugs (nitrates, calcium antagonists and beta-blockers) could be evaluated by exercise radionuclide angiocardiography or exercise echocardiography in the cases of effort angina. The effects of the drugs changing myocardial contractility, preload or afterload could be evaluated by echocardiography in various kinds of heart diseases, including valvular heart biseases. The effect of calcium antagonists in improving diastolic function in hypertrophic cardiomyopathy could be evaluated by echocardiography or Doppler echocardiography. In conclusion, imaging techniqus are valuable and useful methods to evaluate the effects of cardiovascular drugs, by offering various informations. (author)

  2. Evaluation of local anesthetic and antipyretic activities of Cinchona ...

    African Journals Online (AJOL)

    Purpose: To evaluate the local anesthetic and antipyretic activities of an aqueous extract of Cinchona officinalis (C. officinalis) in experimental animal models. Methods: Various doses of the aqueous extract was tested for its local anesthetic activity in guinea pigs and frogs using intracutaneous and plexus anesthesia, ...

  3. 122 evaluation of the quality of locally manufactured antimicrobial

    African Journals Online (AJOL)

    are not available. In order to provide some data, we evaluated the quality of three brands of locally manufactured ... careful control and standardization of the various ... Systems, in Enugu, Optudisc from MEDLABCOP, ... Briefly, a sterilized wire.

  4. The impact of cancer drug wastage on economic evaluations.

    Science.gov (United States)

    Truong, Judy; Cheung, Matthew C; Mai, Helen; Letargo, Jessa; Chambers, Alexandra; Sabharwal, Mona; Trudeau, Maureen E; Chan, Kelvin K W

    2017-09-15

    The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area- or weight-based dosing. Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights. Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs. Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017;123:3583-90. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. Online drug information platform for the public in Hong Kong-Review of local drug information use and needs.

    Science.gov (United States)

    Cheng, F W T; So, S W K; Fung, B W T; Hung, W H; Lee, V W Y

    2018-06-01

    In view of the popularity of Internet usage in Hong Kong, an interactive web-based drug information platform entitled "Ask My Pharmacist - Online University Led drug Enquiry Platform" (AMPOULE) was launched in 2009 to better serve the needs of drug information in Hong Kong. This paper aimed to evaluate the utility of AMPOULE in improving drug-related knowledge among the public and to reassess the needs of the general public in Hong Kong. All enquiries sent via AMPOULE were reviewed. Demographic data, nature of questions and types of drug class covered were analyzed. The workload of pharmacists was examined with respect to the preparation time needed for the enquiry, the lag days to reply and also the timing of enquiry recipient. 2122 enquiries were received from 2009 to 2017. Most enquirers were from Hong Kong (56.6%) and female gender (49.2%). 13% of the concerned subjects were aged over 61-year-old. The most frequent types of questions and medications covered were "Drug Ingredients and Indications" (28.0%) and Adverse Drug Reactions (26.8%) and "Cardiovascular Medication" (21.9%) respectively but these varied in different age groups or enquirer groups. The median time for preparation was 40.0 min (IQR: 25-65 min) while the median time lag was found to be 2.5 days (IQR: 1.0-5.0 days). The number of enquiries received was evenly distributed throughout the day except during 1:00 am to 9:00 am and 7:00 pm to 8:00 pm. AMPOULE has demonstrated that an online platform providing patient-oriented drug information service through the Internet is promising and further promotion is warranted. Current data suggested that the need of different age groups and enquirer groups are different and should therefore be individualized. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions

    Science.gov (United States)

    Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael

    2011-01-01

    Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

  7. [The influence of drug liberation from drug forms on local therapy of infected bone cavities].

    Science.gov (United States)

    Süss, W; Wehr, M

    1984-09-01

    With regard to an optimum local pharmaco-therapy in infected bone cavities, in vitro examinations by means of a flow model based on the half-change method had been performed to liberate Gentamycin from globular embeddings in polymethylmethacrylate. The Gentamycin had been determined in a micro-biological manner. The release behaviour of the polymere carrier could be controlled by adding Polyethylenglycol 400 as softener or butane dioldimethacrylate as wettener. Adding 20 vol.-% of Polyethylenglycol 400, the Gentamycin release could be increased to the 8-fold, whereas the addition of 5 vol.-% of butane dioldimethacrylate resulted in a decrease amounting to 7/8 exit value.

  8. The relevance of the psychological evaluation in drug dependence

    OpenAIRE

    Popescu, G; Negrei, C; B?l?l?u, D; Ciobanu, AM; Baconi, D

    2014-01-01

    Psychological interventions are considered a central part of the individual psychotherapy in the rehabilitation counseling of psychiatrically symptomatic drug-dependent patients during methadone maintenance treatment in community programs. The need for psychological counseling should be evaluated for each individual patient. Medication is an important part of the treatment and individual psychotherapy focuses on the reduction or total cessation of drug use. The Recipient is G.M. 31, sentenced...

  9. The impact of cardiovascular drugs on the efficacy of local anesthesia in dentistry.

    Science.gov (United States)

    Milosavljevic, Мarko J; Jankovic, Slobodan M

    2016-12-01

    Drugs used chronically by patients with diseases of the cardiovascular system (group C of the ATC classification) may act on adrenergic receptors and/or certain ion channels, which gives them the potential to interact with the action of local dental anesthetics. The aim of the study was to investigate the effect of systemically administered chronic cardiovascular medication (oral route) on the efficacy of intraoral local anesthesia in patients with diseases of the cardiovascular system. This was a prospective cohort study which analyzed the efficacy of local terminal anesthesia (onset of anesthesia, duration anesthetized area) in the upper jaw of 70 patients: 40 patients on medication for cardiovascular system disorders and 30 patients who were not using these drugs (the control group). The following cardiovascular drugs were used: beta blockers, angiotensin converting enzyme inhibitors, calcium channel blockers, vasodilatators, diuretics, angiotensin receptor blockers, antiarrhythmics, statins and alfa blockers. The onset of anesthesia on the vestibular side was faster in those taking cardiovascular drugs (40.50±19.87 s) than the control patients (58.93±31.07 s; P = 0.004) and duration of anesthesia on this side was shorter. Although the difference was not significant, it was evident that on vestibular and palatal side the anesthetized area was more rapidly reduced in the patients taking cardiovascular drugs. The duration of cardiovascular therapy also had a significant impact on the anesthetized area. Drugs acting on cardiovascular system may influence the effect of local anesthetics used in dentistry, possibly through interaction with autonomic receptors and ion channels.

  10. Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery

    International Nuclear Information System (INIS)

    Li, Yong-Yong; Li, Lan; Dong, Hai-Qing; Cai, Xiao-Jun; Ren, Tian-Bin

    2013-01-01

    PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ∼ 100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends. Hydrophobic anticancer drug doxorubicin (DOX) with inherent fluorescence was chosen as the model drug, which was found to be efficiently encapsulated into nanomicelles with the encapsulation efficiency at 72.68%. In comparison with the non-functionalized namomicelles, the microscopic observation reveals that PV7 functionalized nanomicelles display a higher cellular uptake, especially into the nucleus of HepG2 cells, due to the nuclear localization signal effects. Both cytotoxicity and apoptosis studies show that the DOX-loaded nanomicelles were more potent than drug nanomicelles without nuclear targeting functionality. It was thus concluded that PV7 functionalized nanomicelles could be a potentially alternative vehicle for nuclear targeting drug delivery. - Highlights: ► A new nuclear targeted drug delivery system based on micelles is developed. ► This micellar system features a core-shell structure with the size peaked at 100 nm. ► PV7, a short peptide sequence, is adopted as a nuclear targeting ligand. ► PV7 functionalized drug loaded micelles are more potent in killing tumor cells

  11. Preparation of hydroxyapatite/poly(lactic acid) hybrid microparticles for local drug delivery

    International Nuclear Information System (INIS)

    Loca, D; Locs, J; Berzina-Cimdina, L

    2013-01-01

    Calcium phosphate (CaP) bioceramic is well known as bioactive and biocompatible material in bone tissue regeneration applications. Apatitic CaP, especially nano sized hydroxyapatite (NHAp), is more similar to the natural apatite presented in the bone tissue than CaP bioceramics. In the current research NHAp was modified using biodegradable polymer – poly(lactic acid) (PLA) to develop composites providing bone regeneration and local drug delivery. NHAp/PLA microcapsules were prepared using solid-in-water-in-oil-in-water (s/w 1 /o/w 2 ) encapsulation technology. The impact of primary and secondary emulsion stability on the emulsion droplet and microparticle properties was evaluated. The stability of final emulsion can be increased by varying the process parameters. Stable s/w 1 /o/w 2 emulsion using 3ml of NHAp suspension, not less than 100ml of 4% PVA water solution and 10ml of 10% PLA solution in dichloromethane can be obtained. S/w 1 /o/w 2 microencapuslation method can be effectively used for the preparation of multi-domain microcapsules achieving high NHAp encapsulation efficacy (93%)

  12. Thermoresponsive nanocomposite gel for local drug delivery to suppress the growth of glioma by inducing autophagy.

    Science.gov (United States)

    Ding, Li; Wang, Qi; Shen, Ming; Sun, Ying; Zhang, Xiangyu; Huang, Can; Chen, Jianhua; Li, Rongxin; Duan, Yourong

    2017-07-03

    Although the treatments of malignant glioma include surgery, radiotherapy and chemotherapy by oral drug administration, the prognosis of patients with glioma remains very poor. We developed a polyethylene glycol-dipalmitoylphosphatidyle- thanoiamine (mPEG-DPPE) calcium phosphate nanoparticles (NPs) injectable thermoresponsive hydrogel (nanocomposite gel) that could provide a sustained and local delivery of paclitaxel (PTX) and temozolomide (TMZ). In addition, the proportion of PTX and TMZ for the optimal synergistic antiglioma effect on C6 cells was determined to be 1:100 (w/w) by the Chou and Talalay method. Our results clearly indicated that the autophagy induced by PTX:TMZ NPs plays an important role in regulating tumor cell death, while autophagy inhibition dramatically reverses the antitumor effect of PTX:TMZ NPs, suggesting that antiproliferative autophagy occurs in response to PTX:TMZ NPs treatment. The antitumor efficacy of the PTX:TMZ NP-loaded gel was evaluated in situ using C6 tumor-bearing rats, and the PTX:TMZ NP-loaded gel exhibited superior antitumor performance. The antitumor effects of the nanocomposite gel in vivo were shown to correlate with autophagic cell death in this study. The in vivo results further confirmed the advantages of such a strategy. The present study may provide evidence supporting the development of nanomedicine for potential clinical application.

  13. Drug Use Evaluation of Three Widely Prescribed Antibiotics in a

    Directory of Open Access Journals (Sweden)

    Mehdi Mohammadi

    2015-10-01

    Full Text Available Background: Drug utilization studies are helpful in understanding the current practice. We have conducted a retrospective study to evaluate the relevant use of a group of most commonly prescribed antibiotics in a teaching hospital in Iran.  The results of this study may be of help for clinicians to improve the patient care.Methods: Patients who received parenteral ceftazidim, vancomycin and amikacin from December2010 to May 2011 were enrolled in this study. Patient’s data including demographic, length of Hospital stay, drug allergy, first and final diagnosis were recorded in a predesigned data collection form. American Hospital Formulary Services (AHFS book were used as a reference for evaluation of study drug indication and dosing according to diagnosis and microbiological culture. Defined Daily Dose (DDD of each drug extracted from Anatomic and Therapeutic Chemical classification system (ATC/DDD and drug usage data evaluated by calculating the ratio of prescribed drug to its DDD.Results: The ratio of prescribed daily dose to DDD was 0.78, 0.95 and 0.86 for amikacin, ceftazidime and vancomycin respectively. Between amikacin group, 43 patients (86% received drug empirically, the number of empiric treatments for ceftazidim and vancomycin were 45(90% and 44 patients (88%. The renal function tests (Blood Urea Nitrogen, Serum Creatinin were evaluated in 56% of amikacin group, 64% in ceftazidime group and 78% in vancomycin group.Conclusion: The results of this study indicate the need to establish continuing medical education (CME courses for physicians to familiarize them with standards required to use and monitor these agents.

  14. Efficacy of local drug delivery of Achyranthes aspera gel in the management of chronic periodontitis: A clinical study

    Directory of Open Access Journals (Sweden)

    Ramanarayana Boyapati

    2017-01-01

    Full Text Available Context: Periodontitis is an inflammatory disease of microbial origin. Locally delivered antimicrobials reduce subgingival flora. Achyranthes aspera gel has antimicrobial, antioxidant, anti-inflammatory, and immunostimulant effects. Aims: To evaluate the efficacy of local drug delivery of A. aspera gel in the management of chronic periodontitis. Materials and Methods: Thirty patients with chronic periodontitis were considered in the study and categorized into two equal groups (Group A: scaling and root planing (SRP with A. aspera gel, Group B: SRP with placebo gel. Patients were enlisted from the Department of Periodontics, Mamata Dental College and Hospital. The clinical parameters (gingival index, bleeding on probing, probing pocket depth, and clinical attachment level were recorded at baseline and 3 months. Statistical Analysis Used: All the obtained data were sent for statistical analyses using SPSS version 18. Results: The periodontitis and the Achyranthes were statistically analyzed. A comparison of clinical parameters for test group and control group from baseline to 3 months was done using paired t-test. Intergroup comparison for both the groups was done using independent sample t-test. Conclusions: A. aspera gel when delivered locally along with SRP showed a beneficial effect. A. aspera gel as a non-surgical local drug delivery system proved to be without any side effects in the management of periodontitis. A. aspera gel has strong anti-inflammatory effects in addition to its antioxidant activity.

  15. Efficacy of local drug delivery of Achyranthes aspera gel in the management of chronic periodontitis: A clinical study.

    Science.gov (United States)

    Boyapati, Ramanarayana; Gojja, Prathibha; Chintalapani, Srikanth; Nagubandi, Kirankumar; Ramisetti, Arpita; Salavadhi, Shyam Sunder

    2017-01-01

    Periodontitis is an inflammatory disease of microbial origin. Locally delivered antimicrobials reduce subgingival flora. Achyranthes aspera gel has antimicrobial, antioxidant, anti-inflammatory, and immunostimulant effects. To evaluate the efficacy of local drug delivery of A. aspera gel in the management of chronic periodontitis. Thirty patients with chronic periodontitis were considered in the study and categorized into two equal groups (Group A: scaling and root planing (SRP) with A. aspera gel, Group B: SRP with placebo gel). Patients were enlisted from the Department of Periodontics, Mamata Dental College and Hospital. The clinical parameters (gingival index, bleeding on probing, probing pocket depth, and clinical attachment level) were recorded at baseline and 3 months. All the obtained data were sent for statistical analyses using SPSS version 18. The periodontitis and the Achyranthes were statistically analyzed. A comparison of clinical parameters for test group and control group from baseline to 3 months was done using paired t -test. Intergroup comparison for both the groups was done using independent sample t -test. A. aspera gel when delivered locally along with SRP showed a beneficial effect. A. aspera gel as a non-surgical local drug delivery system proved to be without any side effects in the management of periodontitis. A. aspera gel has strong anti-inflammatory effects in addition to its antioxidant activity.

  16. Human abuse liability evaluation of CNS stimulant drugs.

    Science.gov (United States)

    Romach, Myroslava K; Schoedel, Kerri A; Sellers, Edward M

    2014-12-01

    Psychoactive drugs that increase alertness, attention and concentration and energy, while also elevating mood, heart rate and blood pressure are referred to as stimulants. Despite some overlapping similarities, stimulants cannot be easily categorized by their chemical structure, mechanism of action, receptor binding profile, effects on monoamine uptake, behavioral pharmacology (e.g., effects on locomotion, temperature, and blood pressure), therapeutic indication or efficacy. Because of their abuse liability, a pre-market assessment of abuse potential is required for drugs that show stimulant properties; this review article focuses on the clinical aspects of this evaluation. This includes clinical trial adverse events, evidence of diversion or tampering, overdoses and the results of a human abuse potential study. While there are different types of human experimental studies that can be employed to evaluate stimulant abuse potential (e.g., drug discrimination, self-administration), only the human abuse potential study and clinical trial adverse event data are required for drug approval. The principal advances that have improved human abuse potential studies include using study enrichment strategies (pharmacologic qualification), larger sample sizes, better selection of endpoints and measurement strategies and more carefully considered interpretation of data. Because of the methodological advances, comparisons of newer studies with historical data is problematic and may contribute to a biased regulatory framework for the evaluation of newer stimulant-like drugs, such as A2 antagonists. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Methodology of investment effectiveness evaluation in the local energy market

    Energy Technology Data Exchange (ETDEWEB)

    Kamrat, W.

    1999-07-01

    The paper presents issues of investment effectiveness evaluation in the local energy market. Results of research presented in the paper are mainly proposing a concept of a methodology which allows the evaluation of investment processes in regional power markets at the decision-making stage. In this respect, selecting a rational investment strategy is an important stage of the entire investment process. In view of criteria of various nature, the construction of a methodology of investment effectiveness bears an especially important meaning for a local decision-maker or investor. It is of particular significance to countries that are undergoing a transition from a centrally planned economy to a market economy. (orig.)

  18. Wireless implantable chip with integrated nitinol-based pump for radio-controlled local drug delivery.

    Science.gov (United States)

    Fong, Jeffrey; Xiao, Zhiming; Takahata, Kenichi

    2015-02-21

    We demonstrate an active, implantable drug delivery device embedded with a microfluidic pump that is driven by a radio-controlled actuator for temporal drug delivery. The polyimide-packaged 10 × 10 × 2 mm(3) chip contains a micromachined pump chamber and check valves of Parylene C to force the release of the drug from a 76 μL reservoir by wirelessly activating the actuator using external radio-frequency (RF) electromagnetic fields. The rectangular-shaped spiral-coil actuator based on nitinol, a biocompatible shape-memory alloy, is developed to perform cantilever-like actuation for pumping operation. The nitinol-coil actuator itself forms a passive 185 MHz resonant circuit that serves as a self-heat source activated via RF power transfer to enable frequency-selective actuation and pumping. Experimental wireless operation of fabricated prototypes shows successful release of test agents from the devices placed in liquid and excited by radiating tuned RF fields with an output power of 1.1 W. These tests reveal a single release volume of 219 nL, suggesting a device's capacity of ~350 individual ejections of drug from its reservoir. The thermal behavior of the activated device is also reported in detail. This proof-of-concept prototype validates the effectiveness of wireless RF pumping for fully controlled, long-lasting drug delivery, a key step towards enabling patient-tailored, targeted local drug delivery through highly miniaturized implants.

  19. Stability and drug dissolution evaluation of Qingkailing soft/hard ...

    African Journals Online (AJOL)

    Purpose: To carry out a post-marketing evaluation of the stability and drug dissolution of ... Stability data from long-term studies showed that within 6 months the ... However, fingerprint pattern statistical analysis showed that the soft capsule is ...

  20. Allergy to local and general anesthetics and to other drugs during surgical procedures

    OpenAIRE

    Ortega, María Claudia; Hospital Universitario San Ignacio; López, Santiago; Hospital Infantil Los Ángeles; Morato, Fabio F.; Hospital de Clínicas, São Paulo, Brasil; Kase Tanno, Luciana; Hospital de Clínicas, São Paulo, Brasil; Ensina, Luis Felipe C.; Hospital de Clínicas, São Paulo, Brasil

    2010-01-01

    Shock and hypersensitivity reactions to local and general anesthetics and to other drugs used during surgical procedures continue being a challenge in clinical practice. Allergic hypersensitivity can vary in presentation and intensity and might manifest itself from mild cutaneous symptoms to death. Las reacciones de choque e hipersensibilidad a los anestésicos locales y generales y a otros medicamentos utilizados durante los procedimientos quirúrgicos, continúan siendo un reto en la prácti...

  1. New indicators of illegal drug use to compare drug user populations for policy evaluation

    Directory of Open Access Journals (Sweden)

    Francesco Fabi

    2013-11-01

    Full Text Available Background: New trends in drug consumption show a trend towards higher poly-use. Epidemiological indicators presently used are mostly based on the prevalence of users of the “main” substances and the ranking of harm caused by drug use is based on a single substance analysis.Methods: In this paper new indicators are proposed; the approach consider the segmentation of the population with respect to the frequency of use in the last 30 days and the harm score of the various substances used by a poly-user. Scoring is based on single substance score table reported in recent papers and principal component analysis is applied to reduce dimensionality. Any user ischaracterized by the two new scores: frequency of use score and poly-use score.Results: The method is applied to the drug user populations interviewed in Communities and Low Threshold Services within the Problem Drug Use 2012 survey in four different European countries. The comparison of the poly-use score cumulative distributions gives insight about behavioural trends of drug use and also evaluate the efficacy of the intervention services. Furthermore, the application of this method to School Population Survey 2011 data allows a definition of the expected behaviour of the poly-drug score for the General Population Survey to be representative.Conclusions: In general, the method is simply and intuitive, and could be applied to surveys containing questions about drug use. A possible limitations could be that the median is chosen for calculating the frequency of use score in questionnaires containing the frequency of drug use in classes.

  2. Evaluation of mean platelet volume in localized scleroderma.

    Science.gov (United States)

    Bahali, Anil Gulsel; Su, Ozlem; Emiroglu, Nazan; Cengiz, Fatma Pelin; Kaya, Mehmet Onur; Onsun, Nahide

    2017-01-01

    Localized scleroderma is a chronic inflammatory skin disease characterized by sclerosis of the dermis and subcutaneous tissue. Platelets play an important role in inflammation. Following activation, platelets rapidly release numerous mediators and cytokines, which contribute to inflammation. To evaluate whether there was any relation between localized scleroderma and platelet parameters. Forty-one patients with localized scleroderma were enrolled in the study. The control group consisted of 30 healthy subjects. The mean platelet volume level in the patient group was 9.9 ± 1.3 fl and in the control group was 7.6 ± 1.1 fl. This difference was statistically significant (pscleroderma. Platelet parameters may be used as markers for evaluating disease severity and inflammatory processes. Thus, there is a need for more detailed and prospective studies.

  3. A scheme for evaluating a local queue warning system.

    NARCIS (Netherlands)

    Botma, H. & Oei, H.-L.

    2018-01-01

    This article outlines a method of evaluating a 'local queue warning system', in principle intended only to warn drivers of unexpected congestion at known discontinuities of the road geomctry (bottleneck) and give them advisory speed indications. A prerequisite for installing this system is therefore

  4. Phenotypic evaluation of growth traits in two Nigerian local chicken ...

    African Journals Online (AJOL)

    A study was conducted to evaluate growth traits, including body weight, body length, chest girth, leg length, shank length and shank circumference, using data obtained from 150 mixed sex birds originating from improved Nigerian local chicken (75 normal feather and 75 naked neck genotypes) of 4 – 16 weeks of age.

  5. Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

    Directory of Open Access Journals (Sweden)

    Alexis M. Ziemba

    2017-05-01

    Full Text Available Affecting approximately 17,000 new people each year, spinal cord injury (SCI is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present studies using a variety of biomaterials, including hydrogels, particles, and fibers/conduits for drug delivery. Subsequently, we discuss how each may be manipulated to optimize drug release during a specific time frame following SCI. Developing polymer biomaterials that can effectively release drug to target specific aspects of SCI pathophysiology will result in more efficacious approaches leading to better regeneration and recovery following SCI.

  6. A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

    International Nuclear Information System (INIS)

    Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

    2010-01-01

    Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

  7. Gamma- scintigraphy in the evaluation of drug delivery systems

    International Nuclear Information System (INIS)

    Shahhosseini, S.; Beiki, D.; Eftekhari, M.

    2003-01-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical delivery systems, particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate radionuclide such as technetium-99m or indium-111 into the formulation or by addition of a non- radioactive isotope such as samarium-152 followed by neutron activation of the final product. Drug delivery systems can be tested in vitro using various techniques like dissolution rate. Since in vitro testing methods are not predictive of in vivo results, such systems should be evaluated in vivo using animal models, especially oral dosage forms. Altered gastrointestinal transit due to individual variation, physiologic factors, or the presence of food may influence bioavailability. Distribution or drug release may be premature or delayed in vivo. Similarly, altered deposition or clearance from other routes of administration such as nasal, ocular, or inhalation may explain drug absorption anomalies. Therefore, there is a growing tendency for new drug delivery systems to be tested, whenever possible, in human subjects in a so called phase 1 clinical evaluation. Gamma- scintigraphy combined with knowledge of physiological and dosage from design can help to identify some of these variables. the resulting insight can be used to accelerate the formulation development process and to ensure success in early clinical trials

  8. VECTOR THEORY AND OPTIMAL CHOICE OF ANTIMICROBIAL DRUG FOR LOCAL WOUND TREATMENT

    Directory of Open Access Journals (Sweden)

    Boyko N. N

    2016-12-01

    Full Text Available Introduction. One of important problems in the field of medicine and pharmacy is an optimal choice among several alternatives. For example, the choice of drugs for treatment among several analogs, selection of excipients among analogs for development of pharmaceutical forms with optimal pharmacological, technological and economical parameters, etc.The aim of the work is to show the possibility of vector theory use for optimal choice of antimicrobial drugs for local wound treatment among analogs taking into account several criteria at the same time. Materials and methods. For our investigation we have chosen ten drugs with antimicrobial properties for local wound treatment in different pharmaceutical forms (ointment, liniment, water and glycerin solution, tincture. We have determined antibacterial activity of drugs by agar well diffusion method on six test-stain microorganisms: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Proteus vulgaris ATCC 4636, Bacillus subtilis ATCC 6633, and Candida albicans ATCC 885-653. Well diameter was 10 mm, the volume of drug in the well was 0.27±0.02 ml, microbial burden of agar upper layer was 107 CFU/ml, and total layer height in Petri dish was 4.0±0.5 mm. In order to integrate various qualitative and quantitative parameters into one index (vector object in multidimensional factors’ space we modify these parameters to non-dimensional normalized values. For this purpose we use a desirability theory. We have chosen the following criteria for optimal choice of the drug: antimicrobial activity (integrated index of drug’s antimicrobial activity, drug’s price, pharmacological and technological index, spectrum of drug’s action on test strains of microorganisms studied. Results and their discussions. Using vector and desirability theory, we have obtained the following range of drugs in decreasing order: Laevomecol ointment, Ioddicerinum, Tincture of Sophora

  9. Poa secunda local collections and commercial releases: A genotypic evaluation.

    Directory of Open Access Journals (Sweden)

    Alanna N Shaw

    Full Text Available The genetics of native plants influence the success of ecological restoration, yet genetic variability of local seed collections and commercial seed releases remains unclear for most taxa. Poa secunda, a common native grass species in Intermountain West grasslands and a frequent component of restoration seed mixes, is one such species. Here, we evaluate the genetic variation of local Poa secunda collections in the context of wild populations and commercial seed releases. We evaluated AFLP markers for seven Poa secunda collections made over a 4000-hectare area and four commercial releases (High Plains, MT-1, Opportunity, and Sherman. We compare the genetic distance and distribution of genetic variation within and between local collections and commercial releases. The extent and patterns of genetic variation in our local collections indicate subtle site differences with most variation occurring within rather than between collections. Identical genetic matches were usually, but not always, found within 5 m2 collection sites. Our results suggest that the genetic variation in two Poa secunda releases (High Plains and MT-1 is similar to our local collections. Our results affirm that guidelines for Poa secunda seed collection should follow recommendations for selfing species, by collecting from many sites over large individual sites.

  10. Evaluation of Food Freshness and Locality by Odor Sensor

    Science.gov (United States)

    Koike, Takayuki; Shimada, Koji; Kamimura, Hironobu; Kaneki, Noriaki

    The aim of this study was to investigate whether food freshness and locality can be classified using a food evaluation system consisting four SnO2-semiconductor gas sensors and a solid phase column, into which collecting aroma materials. The temperature of sensors was periodically changed to be in unsteady state and thus, the sensor information was increased. The parameters (in quefrency band) were extracted from sensor information using cepstrum analysis that enable to separate superimposed information on sinusoidal wave. The quefrency was used as parameters for principal component and discriminant analyses (PCA and DCA) to detect food freshness and food localities. We used three kinds of strawberries, people can perceive its odors, passed from one to three days after harvest, and kelps and Ceylon tea, people are hardly to perceive its odor, corrected from five areas as sample. Then, the deterioration of strawberries and localities of kelps and Ceylon teas were visually evaluated using the numerical analyses. While the deteriorations were classified using PCA or DCA, the localities were classified only by DCA. The findings indicate that, although odorant intensity influenced the method detecting food quality, the quefrency obtained from odorant information using cepstrum analysis were available to detect the difference in the freshness and the localities of foods.

  11. [Evaluation of administration errors of injectable drugs in neonatology].

    Science.gov (United States)

    Cherif, A; Sayadi, M; Ben Hmida, H; Ben Ameur, K; Mestiri, K

    2015-11-01

    Use of injectable drugs in newborns represents more than 90% of prescriptions and requires special precautions in order to ensure more safety and efficiency. The aim of this study is to gather errors relating to the administration of injectable drugs and to suggest corrective actions. This descriptive and transversal study has evaluated 300 injectable drug administrations in a neonatology unit. Two hundred and sixty-one administrations have contained an error. Data are collected by direct observations of administrative act. Errors observed are: an inappropriate mixture (2.6% of cases); an incorrect delivery rate (33.7% of cases); incorrect dilutions (26.7% of cases); error in calculation of the dose to be injected (16.7% of cases); error while sampling small volumes (6.3% of cases); error or omission of administration schedule (1% of cases). These data have enabled us to evaluate administration of injectable drugs in neonatology. Different types of errors observed could be a source of therapeutic inefficiency, extended lengths of stay or iatrogenic drug. Following these observations, corrective actions have been undertaken by pharmacists and consist of: organizing training sessions for nursing; developing an explanatory guide for dilution and administration of injectable medicines, which was made available to the clinical service. Collaborative strategies doctor-nurse-pharmacist can help to reduce errors in the medication process especially during his administration. It permits improvement of injectable drugs use, offering more security and better efficiency and contribute to guarantee ideal therapy for patients. Copyright © 2015. Published by Elsevier Masson SAS.

  12. Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

    Science.gov (United States)

    Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

    2016-09-01

    The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Drug-related webpages classification based on multi-modal local decision fusion

    Science.gov (United States)

    Hu, Ruiguang; Su, Xiaojing; Liu, Yanxin

    2018-03-01

    In this paper, multi-modal local decision fusion is used for drug-related webpages classification. First, meaningful text are extracted through HTML parsing, and effective images are chosen by the FOCARSS algorithm. Second, six SVM classifiers are trained for six kinds of drug-taking instruments, which are represented by PHOG. One SVM classifier is trained for the cannabis, which is represented by the mid-feature of BOW model. For each instance in a webpage, seven SVMs give seven labels for its image, and other seven labels are given by searching the names of drug-taking instruments and cannabis in its related text. Concatenating seven labels of image and seven labels of text, the representation of those instances in webpages are generated. Last, Multi-Instance Learning is used to classify those drugrelated webpages. Experimental results demonstrate that the classification accuracy of multi-instance learning with multi-modal local decision fusion is much higher than those of single-modal classification.

  14. Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery.

    Science.gov (United States)

    Song, Hyun Beom; Lee, Kang Ju; Seo, Il Ho; Lee, Ji Yong; Lee, Sang-Mok; Kim, Jin Hyoung; Kim, Jeong Hun; Ryu, WonHyoung

    2015-07-10

    It has been challenging for microneedles to deliver drugs effectively to thin tissues with little background support such as the cornea. Herein, we designed a microneedle pen system, a single microneedle with a spring-loaded microneedle applicator to provide impact insertion. To firmly attach solid microneedles with 140 μm in height at the end of macro-scale applicators, a transfer molding process was employed. The fabricated microneedle pens were then applied to mouse corneas. The microneedle pens successfully delivered rhodamine dye deep enough to reach the stromal layer of the cornea with small entry only about 1000 μm(2). When compared with syringes or 30 G needle tips, microneedle pens could achieve more localized and minimally invasive delivery without any chances of perforation. To investigate the efficacy of microneedle pens as a way of drug delivery, sunitinib malate proven to inhibit in vitro angiogenesis, was delivered to suture-induced angiogenesis model. When compared with delivery by a 30 G needle tip dipped with sunitinib malate, only delivery by microneedle pens could effectively inhibit corneal neovascularization in vivo. Microneedle pens could effectively deliver drugs to thin tissues without impairing merits of using microneedles: localized and minimally invasive delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Derangement of lipid profile in antiepileptic drugs treated patients in local population

    International Nuclear Information System (INIS)

    Zuberi, N.A.; Perveen, T.

    2012-01-01

    adult epileptic patients. Anti-epileptic drugs alter the BMI and so it could potentially facilitate the development of diabetes mellitus. Long term prospective studies are required to evaluate the risk of atherosclerosis caused by alteration in serum lipid levels which may lead to the cardiovascular disease. (author)

  16. Evaluation of the Drug Treatment and Persistence of Onychomycosis

    Directory of Open Access Journals (Sweden)

    Andrew W. Campbell

    2004-01-01

    Full Text Available Onychomycosis is a common nail disease responsible for approximately 50% of diseases of the nail. It occurs more in the elderly, though several cases have been reported among children. Several factors influence, such as climate, geography, and migration. The two dermatophytes most commonly implicated in onychomycosis are Trichophyton rubrum and T. mentagrophytes, accounting for more than 90% of onychomycoses. Nonetheless, several other toxigenic molds have been implicated. For convenience, onychomycosis is divided into four major clinical presentations: distal subungal, which is the most common form of the disease; proximal subungal, which is the most common form found in patients with human immunodeficiency virus infection; superficial; and total dystrophic onychomycosis. Epidemiology of onychomycosis in adults and children is evaluated and the most common clinical symptoms addressed. Although the risk factors are discussed, the multifactorial nature of onychomycosis makes this inexhaustible. The diagnosis and treatments are difficult and the choice of appropriate antifungal drugs complex and require the knowledge of the chemical structures of the metabolites of the molds that cause onychomycosis and their interaction with the antifungal drugs. This is true because most of the antifungal drugs are derived from mold/fungal metabolism. Treatment with griseofulvin and amphotericin is displaced by the use of newer drugs from azole compounds, pyrimidines, and allylamines derivatives. Amorolfine, itraconazole, and ciclopirox nail lacquer solution 8 have gained support globally, but the side effects, drug resistance, and persistence of the disease are still a serious concern to the patients, just as economics and quality of life. Hence, the search for safer and more efficacious drug treatments are continuing.

  17. Drug interactions evaluation: An integrated part of risk assessment of therapeutics

    International Nuclear Information System (INIS)

    Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping; Huang, Shiew-Mei

    2010-01-01

    Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance ( (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf)) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industry and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a 'Drug Development and Drug Interactions' website to provide up-to-date information regarding evaluation of drug interactions ( (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm)). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.

  18. Local Intravascular Drug Delivery: In Vitro Comparison of Three Catheter Systems

    International Nuclear Information System (INIS)

    Alfke, Heiko; Wagner, Hans-Joachim; Calmer, Christian; Klose, Klaus Jochen

    1998-01-01

    Purpose: The aim of this in vitro study was to compare different catheter systems for local drug delivery with respect to the penetration depth of a biotin marker solution delivered into the vessel wall. Methods: Post-mortem carotid arteries from pigs were locally infused with a biotin solution using three different catheter systems. With all catheters (microporous balloon catheter, hydrogel-coated balloon catheter, and spiral balloon catheter) we used the same pressure of 405 kPa (4 atm) and infusion times of 60, 90, and 300 sec. After infusion the arteries were histologically prepared and stained using a biotin-specific method. With a light microscope an observer, blinded to the catheter type, scored the amount of biotin within the vessel wall, measured as staining intensity, and the penetration depth of the biotin. Results: Delivery with the hydrogel-coated balloon catheter was limited to the intima and the innermost parts of the media. The spiral balloon and microporous balloon catheter showed both a deeper penetration and a larger amount of delivered biotin compared with the hydrogel catheter, with a slightly deeper penetration using the microporous catheter. The penetration depth showed a correlation with infusion time for the spiral balloon and microporous catheters, but not for the hydrogel-coated catheter. Conclusion: Different catheter designs lead to different patterns of local drug delivery. The differences in penetration depth and amount of the substance delivered to the vessel wall should be known and might be useful for targeting specific areas within the vessel wall

  19. [Protective factors for preventing the use of drugs in the families of a Colombia locality].

    Science.gov (United States)

    Arias, Núbia Medina; Ferriani, Maria das Graças Carvalho

    2010-01-01

    The aim of this study was to analyze the protective factors that prevent drug use in the families of children who attend Community Homes of Family Well-being in a small Colombian locality. This was a quantitative, descriptive, transversal study, with 256 families constituting the sample. Data were collected through a self-applied questionnaire throughout March and April 2007. Protective factors found included demonstrations of affection toward the children, playing with them and talking to them about things they like, open communication, decision making as a couple, flexibility of the nursing process, and establishment of rules. However, some risk factors were also found, such as consumption of legal drugs such as cigarettes and alcohol, and in a low percentage, consumption of illicit drugs. A high percentage of families consider that drug use must be prevented in the first years of life, by the parents. The protective factors found require reinforcement as they are not very strong, and the risk factors must be controlled to turn them into protective factors.

  20. Nano materials for the Local and Targeted Delivery of Osteoarthritis Drugs

    International Nuclear Information System (INIS)

    Periyasamy, P.C.; Leijten, J.C.H.; Dijkstra, P.J.; Karperien, M.; Post, J.N.

    2012-01-01

    Nano technology has found its potential in every possible field of science and engineering. It offers a plethora of options to design tools at the nanometer scale, which can be expected to function more effectively than micro- and macro systems for specific applications. Although the debate regarding the safety of synthetic nano materials for clinical applications endures, it is a promising technology due to its potential to augment current treatments. Various materials such as synthetic polymer, biopolymers, or naturally occurring materials such as proteins and peptides can serve as building blocks for adaptive nano scale formulations. The choice of materials depends highly on the application. We focus on the use of nanoparticles for the treatment of degenerative cartilage diseases, such as osteoarthritis (OA). Current therapies for OA focus on treating the symptoms rather than modifying the disease. The usefulness of OA disease modifying drugs is hampered by side effects and lack of suitable drug delivery systems that target, deliver, and retain drugs locally. This challenge can be overcome by using nano technological formulations. We describe the different nano drug delivery systems and their potential for cartilage repair. This paper provides the reader basal understanding of nano materials and aims at drawing new perspectives on the use of existing nano technological formulations for the treatment of osteoarthritis.

  1. Evaluation of fracture mode for local wall-thinned pipes

    International Nuclear Information System (INIS)

    Herman, Irwan; Suzuki, Tomohisa; Sato, Yasumoto; Meshii, Toshiyuki

    2007-01-01

    In this study, by referring to our burst pressure tests results, firstly, the effects of flaw length δ z and pipe size (mean radius R) on burst pressure p f were investigated by using Finite Element Method (FEM). Then, fracture mode evaluation was made by using history data of strain ratio ε z /ε θ along with load increment. Furthermore, the effect of flaw depth t 1 on fracture mode was studied and finally, the evaluation method of fracture mode for local wall-thinned pipes was introduced. (author)

  2. Improvement of survival in C6 rat glioma model by a sustained drug release from localized PLGA microspheres in a thermoreversible hydrogel.

    Science.gov (United States)

    Ozeki, Tetsuya; Kaneko, Daiki; Hashizawa, Kosuke; Imai, Yoshihiro; Tagami, Tatsuaki; Okada, Hiroaki

    2012-05-10

    A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature. Therefore, when this formulation is injected into the brain tumor, the PLGA microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or vincristine (VCR)) were incorporated into PLGA microspheres to prepare drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In addition, VCR/PLGA microspheres showed a higher sustained release profile than CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic effect (mean survival) was evaluated in the C6 rat glioma model (control group, 18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the glioma therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Evaluation and comparison of mammalian subcellular localization prediction methods

    Directory of Open Access Journals (Sweden)

    Fink J Lynn

    2006-12-01

    Full Text Available Abstract Background Determination of the subcellular location of a protein is essential to understanding its biochemical function. This information can provide insight into the function of hypothetical or novel proteins. These data are difficult to obtain experimentally but have become especially important since many whole genome sequencing projects have been finished and many resulting protein sequences are still lacking detailed functional information. In order to address this paucity of data, many computational prediction methods have been developed. However, these methods have varying levels of accuracy and perform differently based on the sequences that are presented to the underlying algorithm. It is therefore useful to compare these methods and monitor their performance. Results In order to perform a comprehensive survey of prediction methods, we selected only methods that accepted large batches of protein sequences, were publicly available, and were able to predict localization to at least nine of the major subcellular locations (nucleus, cytosol, mitochondrion, extracellular region, plasma membrane, Golgi apparatus, endoplasmic reticulum (ER, peroxisome, and lysosome. The selected methods were CELLO, MultiLoc, Proteome Analyst, pTarget and WoLF PSORT. These methods were evaluated using 3763 mouse proteins from SwissProt that represent the source of the training sets used in development of the individual methods. In addition, an independent evaluation set of 2145 mouse proteins from LOCATE with a bias towards the subcellular localization underrepresented in SwissProt was used. The sensitivity and specificity were calculated for each method and compared to a theoretical value based on what might be observed by random chance. Conclusion No individual method had a sufficient level of sensitivity across both evaluation sets that would enable reliable application to hypothetical proteins. All methods showed lower performance on the LOCATE

  4. The relevance of the psychological evaluation in drug dependence.

    Science.gov (United States)

    Popescu, G; Negrei, C; Bălălău, D; Ciobanu, A M; Baconi, D

    2014-01-01

    Psychological interventions are considered a central part of the individual psychotherapy in the rehabilitation counseling of psychiatrically symptomatic drug-dependent patients during methadone maintenance treatment in community programs. The need for psychological counseling should be evaluated for each individual patient. Medication is an important part of the treatment and individual psychotherapy focuses on the reduction or total cessation of drug use. The Recipient is G.M. 31, sentenced to a seven-year term of imprisonment for trafficking and use of and high-risk drugs, diagnosed on admission with opioid and methadone dependence, withdrawal syndrome. Following the observation and psychological evaluation, psychiatric and clinical examination, initiation of methadone substitution treatment was recommended, according to the following regimen: twelve 2.5 mg tablets for the first 2 days, followed by increase with about 5 mg per week until the complete remission of withdrawal symptoms, stabilization of the dose but not exceeding 200 mg methadone hydrochloride per day. Specialist monitoring, specialized counseling and individual and group psychotherapy were provided.

  5. Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver.

    NARCIS (Netherlands)

    Klomp, D.W.J.; Laarhoven, H.W.M. van; Kentgens, A.P.M.; Heerschap, A.

    2003-01-01

    Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for

  6. Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver

    NARCIS (Netherlands)

    Klomp, Dennis W. J.; van Laarhoven, Hanneke W. M.; Kentgens, Arno P. M.; Heerschap, Arend

    2003-01-01

    Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for

  7. Predicting changes in drug use and treatment entry for local programs: a case study.

    Science.gov (United States)

    Flaherty, E W; Olsen, K; Bencivengo, M

    1980-01-01

    Recent sharp decline in treatment admissions by opiate abusers stimulated the conduct of a study designed to provide timely data to treatment system administrators for the next cycle of program and budgetary planning. The process of designing the study involved definition of required study characteristics, review of four categories of drug abuse research, and generation of seven locally relevant hypotheses. Interviews were conducted with 335 heroin adicts: 196 new admissions to treatment and 139 "street" addicts not currently in treatment. Major findings were a marked reduction in the quality, availability, and price of heroin; very negative perceptions of methadone maintenance, especially by female respondents; decline in heroin popularity and increase in reported use of alcohol, amphetamines, and barbiturates; and differing perceptions of treatment by sex of respondent. Response patterns suggest that users who are not entering treatment are less "strung-out than those entering treatment because of decline in availability and quality of heroin and consequent increased mixing of drugs. The emphasis in the report is on the conduct of a study which can be timely, feasible, and useful to local planners. The study weaknesses and recommended remedies are discussed, as well as the characteristics which made the findings immediately useful to administrators and planners.

  8. Engineering and evaluating drug delivery particles in microfluidic devices.

    Science.gov (United States)

    Björnmalm, Mattias; Yan, Yan; Caruso, Frank

    2014-09-28

    The development of new and improved particle-based drug delivery is underpinned by an enhanced ability to engineer particles with high fidelity and integrity, as well as increased knowledge of their biological performance. Microfluidics can facilitate these processes through the engineering of spatiotemporally highly controlled environments using designed microstructures in combination with physical phenomena present at the microscale. In this review, we discuss microfluidics in the context of addressing key challenges in particle-based drug delivery. We provide an overview of how microfluidic devices can: (i) be employed to engineer particles, by providing highly controlled interfaces, and (ii) be used to establish dynamic in vitro models that mimic in vivo environments for studying the biological behavior of engineered particles. Finally, we discuss how the flexible and modular nature of microfluidic devices provides opportunities to create increasingly realistic models of the in vivo milieu (including multi-cell, multi-tissue and even multi-organ devices), and how ongoing developments toward commercialization of microfluidic tools are opening up new opportunities for the engineering and evaluation of drug delivery particles. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Noninvasive, localized, and transient brain drug delivery using focused ultrasound and microbubbles

    Science.gov (United States)

    Choi, James J.

    In the United States, Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancer caused 72,432, 19,566 and 12,886 deaths in 2006, respectively. Whereas the number of deaths due to major disorders such as heart disease, stroke, and prostate cancer have decreased since 2006, deaths attributed to AD, PD, and brain cancer have not. Treatment options for patients with CNS disorders remain limited despite significant advances in knowledge of CNS disease pathways and development of neurologically potent agents. One of the major obstacles is that the cerebral microvasculature is lined by a specialized and highly regulated blood-brain barrier (BBB) that prevents large agents from entering the brain extracellular space. The purpose of this dissertation is to design a noninvasive, localized, and transient BBB opening system using focused ultrasound (FUS) and determine ultrasound and microbubble conditions that can effectively and safely deliver large pharmacologically-relevant-sized agents to the brain. To meet this end, an in vivo mouse brain drug delivery system using a stereotactic-based targeting method was developed. FUS was applied noninvasively through the intact skin and skull, which allowed for long-term and high-throughput studies. With this system, more than 150 mice were exposed to one of 31 distinct acoustic and microbubble conditions. The feasibility of delivering a large MRI contrast agent was first demonstrated in vivo in both wild-type and transgenic Alzheimer's disease model (APP/PS1) mice. A wide range of acoustic and microbubble conditions were then evaluated for their ability to deliver agents to a target region. Interestingly, the possible design space of parameters was found to be vast and different conditions resulted in distinct spatial distributions and doses delivered. In particular, BBB opening was shown to be dependent on the microbubble diameter, acoustic pressure, pulse repetition frequency (PRF), and pulse length (PL). Each set of

  10. Local tolerance testing of parenteral drugs: how to put into practice.

    Science.gov (United States)

    Jochims, Karin; Kemkowski, Joerg; Nolte, Thomas; Bartels, Thomas; Heusener, Alexander

    2003-10-01

    Notwithstanding that there are national and international guidelines about local tolerance testing of parenteral drugs in animals, in particular to mention CPMP/SWP/2145/00 (Note for Guidance on Non-Clinical Local Tolerance Testing of Medicinal Products), very heterogeneous study designs have been established in the past. A working group including experts of the leading pharmaceutical industry from German-language countries, named "Arbeitskreis Lokale Verträglichkeit," has been intensively discussing the experimental procedures in detail for a period of six years and has been considering their pros and cons. This team of experts now feels confident to give some recommendations for study conduct besides describing different materials and methods for this type of toxicological study. Special knowledge from toxicologists as well as pathologists from our working group has been taken into account. This paper deals with choice of species, number of animals used, controls, administration sites, volumes, rate and frequency, length of observation period, termination, clinical, macroscopic and histopathological examinations and, finally, overall assessment criteria and conclusion. Our purpose is that this paper may be of value for: *The study director who is inexperienced in the conduction of local tolerance testing and who may need a standard design as his first step into this new field. *The well-versed study director who would like to know how others have done in the past, who may examine self-critically his own practice and who is open to our team's recommendations, tips and tricks from practice. *The specialist at a regulatory authority who, finally, reviews study reports, assesses their format and content and, above all, decides on the approval of a drug product.

  11. Design of colon targeting drug delivery systems using natural polymeric carriers and their evaluation by gamma scintigraphy technique

    International Nuclear Information System (INIS)

    Soni, P.S.; Sawarkar, S.P.; Deshpande, S.G.; Bajaj, A.N.

    2004-01-01

    Of late, there has been a great awareness in the concept of drug targeting and delivery to a specific site (organ, tissue or cell) in the body to maximize therapeutic effect and reduce toxicity. The various approaches of site-specific drug delivery are implantable pumps, adhesive patches impregnated with drugs, vesicle enclosed drugs and drug carriers. Colonic drug delivery is intended for local and systemic treatment in the diseases of colon like inflammatory bowel conditions. Several approaches using viz. pro-drugs, biodegradable polymers and pH sensitive polymer coatings have been used to achieve colonic delivery. Natural polysaccarides like guar gum and pectin are promising candidates because they are susceptible to degradation by colonic bacteria and thus can release the entrapped drug in the colonic region. These indigenous natural polymers are cheaply and readily available. They comprise of polygalactouronic acid and refractory to host enzymes present in the upper gastrointestinal tract and are degraded by the enzymes produced by the colonic microflora. They were evaluated as a colonic carrier using 5-amino salicylic acid (5-ASA) as a model drug. After successful in vitro testing, gamma scintigraphy technique was used to assess in-vivo behavior of the colon specific drug delivery after a coat of Guar gum and Pectin

  12. Anxiety and dysthymia: local prevalence estimates based on drug prescriptions by general practitioners in Turin (Italy).

    Science.gov (United States)

    Mamo, C; Farina, E; Cicio, R; Fanì, M

    2014-01-01

    The aim of the study was to obtain local estimates of the prevalence of anxiety and dysthymic disorders among attendees of primary care at local level, useful to pursue a better management of the health care services. The study was conducted in the Health District no. 2 of Turin (industrial town in northwest Italy). The criteria for identification of cases were based on the drugs prescriptions made by general practitioners (GPs), selected in order to assure high specificity. The study involved 86 physicians (with 87,885 attendees). As expected, the crude and standardized prevalences were higher in women (anxiety: 2.9% vs 1.3% in men; dysthymia: 3.8% vs 1.7% in men), with a peak in women aged over 75 yrs (anxiety: 4.8%; dysthymia: 6.2%). In comparison to male GPs, female GPs had an higher prevalence of patients with anxious disorders, whereas the prevalences of dysthymia were similar. Despite the discussed limitations, the used methodology allows to obtain sufficiently reliable estimates of prevalence of common mental disorders at local level, providing informations useful for organizing the primary care in the Health district.

  13. [Characteristics of local human skeleton reactions to microgravity and drug treatment of osteoporosis in clinic].

    Science.gov (United States)

    Oganov, V S; Skripnikova, I A; Novikov, V E; Bakulin, A V; Kabitskaia, O E; Murashko, L M

    2011-01-01

    Analysis of the results of long-term investigations of bones in cosmonauts flown on the orbital station MIR and International space station (n = 80) was performed. Theoretically predicted (evolutionary predefined) change in mass of different skeleton bones was found to correlate (r = 0.904) with position relatively the Earth's gravity vector. Vector dependence of bone loss ensues from local specificity of expression of bone metabolism genes which reflects mechanic prehistory of skeleton structures in the evolution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss attested by the dependence of bone loss rate on polymorphism of certain bone metabolism markers. Parameters of one and the other orbital vehicle did not modulate individual-specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus-unique spatial structure of distribution of noncollagenous proteins responsible for position regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotrophic intervention into areas of bustling resorption.

  14. Power Consumption Evaluation of Distributed Computing Network Considering Traffic Locality

    Science.gov (United States)

    Ogawa, Yukio; Hasegawa, Go; Murata, Masayuki

    When computing resources are consolidated in a few huge data centers, a massive amount of data is transferred to each data center over a wide area network (WAN). This results in increased power consumption in the WAN. A distributed computing network (DCN), such as a content delivery network, can reduce the traffic from/to the data center, thereby decreasing the power consumed in the WAN. In this paper, we focus on the energy-saving aspect of the DCN and evaluate its effectiveness, especially considering traffic locality, i.e., the amount of traffic related to the geographical vicinity. We first formulate the problem of optimizing the DCN power consumption and describe the DCN in detail. Then, numerical evaluations show that, when there is strong traffic locality and the router has ideal energy proportionality, the system's power consumption is reduced to about 50% of the power consumed in the case where a DCN is not used; moreover, this advantage becomes even larger (up to about 30%) when the data center is located farthest from the center of the network topology.

  15. Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

    Directory of Open Access Journals (Sweden)

    José Cabrita

    2017-04-01

    Full Text Available Observational epidemiological studies have been used in the medicines context for more than 40 years, contributing to characterize drug use patterns and safety, efficacy and effectiveness profiles. Its use has been increased in recognition of the clinical trials limitations to assess the therapeutic and iatrogenic potential of the medicines after its commercialization. The evolution of the regulatory framework for pharmacovigilance, requiring post-marketing studies, post-authorization safety studies (PASS and the post-authorization efficacy studies (PAES to approve certain drugs, reinforced the importance of observational pharmacoepidemiology for the characterization of the medicines safety and effectiveness profiles. Pharmacoepidemiological research can be carried out from field studies designed to obtain the necessary information or in databases with health records of population samples that already contain the information. This 2nd option is more efficient and more and more frequent. Although, observational research from field studies continues to have its space, the increasing availability of databases allowed a new development to observational pharmacoepidemiology. Indeed, access to automated records databases with up-to-date information on medical prescriptions and global health care to representative population samples with long follow-up periods is a valuable tool for the study of drug use patterns and therapeutic and iatrogenic potential in routine clinical practice. In this context, observational pharmacoepidemiology reinforces its role as a scientific area particularly suitable for evaluating the safety and the effectiveness of the medicines in the “real world”, making a relevant contribution to overcome the gap in translating the evidence from the clinical trials for clinical practice.

  16. The law on the streets: Evaluating the impact of Mexico's drug decriminalization reform on drug possession arrests in Tijuana, Mexico.

    Science.gov (United States)

    Arredondo, J; Gaines, T; Manian, S; Vilalta, C; Bañuelos, A; Strathdee, S A; Beletsky, L

    2018-04-01

    In 2009, Mexican Federal Government enacted "narcomenudeo" reforms decriminalizing possession of small amounts of drugs, delegating prosecution of retail drug sales to the state courts, and mandating treatment diversion for habitual drug users. There has been insufficient effort to formally assess the decriminalization policy's population-level impact, despite mounting interest in analagous reforms across the globe. Using a dataset of municipal police incident reports, we examined patterns of drug possession, and violent and non-violent crime arrests between January 2009 and December 2014. A hierarchical panel data analysis with random effects was conducted to assess the impact of narcomenudeo's drug decriminalization provision. The reforms had no significant impact on the number of drug possession or violent crime arrests, after controlling for other variables (e.g. time trends, electoral cycles, and precinct-level socioeconomic factors). Time periods directly preceding local elections were observed to be statistically associated with elevated arrest volume. Analysis of police statistics parallel prior findings that Mexico's reform decriminalizing small amounts of drugs does not appear to have significantly shifted drug law enforcement in Tijuana. More research is required to fully understand the policy transformation process for drug decriminalization and other structural interventions in Mexico and similar regional and international efforts. Observed relationship between policing and political cycles echo associations in other settings whereby law-and-order activities increase during mayoral electoral campaigns. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Toxicological evaluation of some Malaysian locally processed raw food products.

    Science.gov (United States)

    Sharif, R; Ghazali, A R; Rajab, N F; Haron, H; Osman, F

    2008-01-01

    Malaysian locally processed raw food products are widely used as main ingredients in local cooking. Previous studies showed that these food products have a positive correlation with the incidence of cancer. The cytotoxicity effect was evaluated using MTT assay (3-(4,5-dimetil-2-thiazolil)-2,5-diphenyl-2H-tetrazolium bromide) against Chang liver cells at 2000 microg/ml following 72 h incubation. Findings showed all methanol extracts caused a tremendous drop in the percentage of cell viability at 2000 microg/ml (shrimp paste - 41.69+/-3.36%, salted fish - 37.2+/-1.06%, dried shrimp - 40.32+/-1.8%, pfood showed that shrimp paste did not comply with the protein requirement (Food Act 1983. Salt was found in every sample with the highest percentage being detected in shrimp paste which exceeded 20%. Following heavy metal analysis (arsenic, cadmium, lead and mercury), arsenic was found in every sample with dried shrimps showing the highest value as compared to the other samples (6.16 mg/kg). In conclusion, several food extracts showed cytotoxic effect but did not cause DNA damage against Chang liver cells. Salt was found as the main additive and arsenic was present in every sample, which could be the probable cause of the toxicity effects observed.

  18. Evaluation of radiolabeled ruthenium compounds as tumor-localizing agents

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Richards, P.; Meinken, G.E.; Som, P.; Atkins, H.L.; Larson, S.M.; Grunbaum, Z.; Rasey, J.S.; Clarke, M.H.; Dowling, M.

    1979-01-01

    This work introduces a new class of radiopharmaceuticals based on ruthenium-97. The excellent physical properties of Ru-97, the high chemical reactivity of Ru, the potential antitumor activity of several Ru coordination compounds, and BLIP production of Ru-97, provide a unique combination for the application of this isotope in nuclear oncology. A systematic study was undertaken on the synthesis, characterization, and evaluation of a number of ruthenium-labeled compounds. In a variety of animal tumor models, several compounds show considerable promise as tumor-localizing agents when compared to gallium-67 citrate. The compounds studied (with Ru in different oxidation states) include ionic Ru, a number of hydrophilic and lipophilic chelates, and various ammine derivatives

  19. In vitro evaluation of dendrimer prodrugs for oral drug delivery.

    Science.gov (United States)

    Najlah, Mohammad; Freeman, Sally; Attwood, David; D'Emanuele, Antony

    2007-05-04

    Dendrimer-based prodrugs were used to enhance the transepithelial permeability of naproxen, a low solubility model drug. The stability of the dendrimer-naproxen link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM) dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity of conjugates towards Caco-2 cells was determined and the transport of the conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in 50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2 cells for 3h. Permeability studies showed a significant enhancement in the transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the highest permeability. Dendrimer-based prodrugs with appropriate linkers have potential as carriers for the oral delivery of low solubility drugs such as naproxen.

  20. G‐LoSA: An efficient computational tool for local structure‐centric biological studies and drug design

    Science.gov (United States)

    2016-01-01

    Abstract Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G‐LoSA. G‐LoSA aligns protein local structures in a sequence order independent way and provides a GA‐score, a chemical feature‐based and size‐independent structure similarity score. Our benchmark validation shows the robust performance of G‐LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure‐centric comparative biology studies. In particular, G‐LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G‐LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer‐aided drug design. We hope that G‐LoSA can be a useful computational method for exploring interesting biological problems through large‐scale comparison of protein local structures and facilitating drug discovery research and development. G‐LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. PMID:26813336

  1. G-LoSA: An efficient computational tool for local structure-centric biological studies and drug design.

    Science.gov (United States)

    Lee, Hui Sun; Im, Wonpil

    2016-04-01

    Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G-LoSA. G-LoSA aligns protein local structures in a sequence order independent way and provides a GA-score, a chemical feature-based and size-independent structure similarity score. Our benchmark validation shows the robust performance of G-LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure-centric comparative biology studies. In particular, G-LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G-LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer-aided drug design. We hope that G-LoSA can be a useful computational method for exploring interesting biological problems through large-scale comparison of protein local structures and facilitating drug discovery research and development. G-LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. © 2016 The Protein Society.

  2. Development and evaluation of an electronic drug and therapeutics bulletin.

    Science.gov (United States)

    Alderman, Christopher P

    2002-10-01

    To describe the development, implementation, and initial evaluation of a paperless drug and therapeutics bulletin that is distributed by electronic mail from the pharmacy department of an Australian teaching hospital. A standardized format for the bulletin was designed and approved in February 2001. The aim of the bulletin is to facilitate the timely dissemination of concise, factual information about issues of current interest in therapeutics, drug safety, and the cost-effective use of medicines. A simple and attractive graphic design was chosen, and the hospital's clinical pharmacists and drug information staff developed an initial bank of content during the period immediately preceding the launch. The bulletin is presented as a 1-page, read-only file in Word for Windows format and was initially distributed by electronic mail to all users of the hospital's computerized communication network. As the popularity of the bulletin increased, healthcare practitioners from outside of the hospital began to request permission for inclusion on the circulation list, and the content was frequently forwarded by E-mail to workers in other hospitals and community-based settings. The bulletin is now distributed to pharmacists around Australia via 2 separate moderated discussion lists, one of which provides an archive site for previous editions. Healthcare workers in Singapore, the US, Canada, and New Zealand also receive the bulletin, which is now also abstracted by a major Australian pharmacy journal. A readership survey (also electronically distributed) was used to seek feedback after the publication of the first 12 editions. Readers indicated a high level of satisfaction with the content, format, and frequency of distribution of the materials. Although the concept and execution of this project was relatively simple, an extensive literature review did not reveal any previously published reports describing this type of approach to the distribution of a pharmacy bulletin. The

  3. Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

    International Nuclear Information System (INIS)

    Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

    2010-01-01

    The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

  4. Pharmaceutical evaluation of different shampoo brands in local Saudi market

    Directory of Open Access Journals (Sweden)

    Bushra T. AlQuadeib

    2018-01-01

    Full Text Available Shampooing is the most common form of hair treatment. Shampoos are primarily products aimed at cleansing the hair and scalp. There are many brands of shampoos in Saudi Arabia, available from different sources, locally and imported from other countries. This study aims to investigate whether such brands comply with the Saudi standard specifications for shampoos, issued by the National Center for Specifications and Standards, and to what extent these specifications are applied. Six shampoo brands were randomly collected from Riyadh market (Pantene®, Sunsilk®, Herbal essences®, Garnier Ultra Doux®, Syoss® and L'Oreal Elvive®. The selected shampoos were evaluated according to their physicochemical properties, including organoleptic characterization, pH measurement, percentage of solid content, rheological measurements, dirt dispersion level, foaming ability and foam stability, and surface tension. All shampoos had a good percentage of solids, excellent foam formation with stable foam and a highly viscous nature. Regarding the pH measurement, all shampoo samples were within the specified range with good wetting ability. Keywords: Shampoo, Physicochemical approach, Evaluation

  5. Design and Evaluation of Chitosan-Based Novel pHSensitive Drug ...

    African Journals Online (AJOL)

    Design and Evaluation of Chitosan-Based Novel pHSensitive Drug Carrier for Sustained ... Scanning electron microscopy(SEM),Raman spectroscopy for particle size analysis. Swelling ratio, Effect of drug loading on encapsulation efficiency

  6. Stability and drug dissolution evaluation of Qingkailing soft/hard ...

    African Journals Online (AJOL)

    HPLC-DAD) method was developed ... stability and drug dissolution, which may affect the biopharmaceutics and the clinical effects of the drug. ... behavior may also affect the pharmacokinetic ..... of enzymes and intrinsic factors in stomach and.

  7. Systematic approach to treat chronic osteomyelitis through localized drug delivery system: Bench to bed side

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Rupnarayan [Department of Plastic Surgery, R. G. Kar Medical College and Hospital (RGKMCH), Kolkata 700004 (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Biocermics and Coating Division, CSIR — Central Glass and Ceramic Research Institute (CSIR-CGCRI), Kolkata 700032 (India); Nandi, Samit Kumar, E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences (WBUAFS), Kolkata 700037 (India); Basu, Debabrata [Biocermics and Coating Division, CSIR — Central Glass and Ceramic Research Institute (CSIR-CGCRI), Kolkata 700032 (India)

    2013-10-15

    Chronic osteomyelitis is a challenging setback to the orthopedic surgeons in deciding an optimal therapeutic strategy. Conversely, patients feel frustrated of the therapeutic outcomes and development of adverse drug effects, if any. Present investigation deals with extensive approach incorporating in vivo animal experimentation and human application to treat chronic osteomyelitis, using antibiotic loaded porous hydroxyapatite scaffolds. Micro- to macro-porous hydroxyapatite scaffolds impregnated with antibiotic ceftriaxone–sulbactam sodium (CFS) were fabricated and subsequently evaluated by in vivo animal model after developing osteomyelitis in rabbit tibia. Finally 10 nos. of human osteomyelitis patients involving long bone and mandible were studied for histopathology, radiology, pus culture, 3D CT etc. up to 8–18 months post-operatively. It was established up to animal trial stage that 50N50H samples [with 50–55% porosity, average pore size 110 μm, higher interconnectivity (10–100 μm), and moderately high drug adsorption efficiency (50%)] showed efficient drug release up to 42 days than parenteral group based on infection eradication and new bone formation. In vivo human bone showed gradual evidence of new bone formation and fracture union with organized callus without recurrence of infection even after 8 months. This may be a new, alternative, cost effective and ideal therapeutic strategy for chronic osteomyelitis treatment in human patients. - Highlights: • Chronic osteomyelitis is challenging setback to decide optimal therapeutic strategy. • Micro- to macro-porous antibiotic CFS impregnated HAp scaffolds were fabricated. • Complete in vivo animal trial done after developing osteomyelitis in rabbit tibia. • Clinical trial showed fracture union without recurrence of infection after 8 months. • This may be a new, alternative, cost effective and ideal therapeutic strategy.

  8. Evaluating and Valuing Drugs for Rare Conditions: No Easy Answers.

    Science.gov (United States)

    Ollendorf, Daniel A; Chapman, Richard H; Pearson, Steven D

    2018-05-01

    We find ourselves in an era of unprecedented growth in the development and use of so-called "orphan" drugs to treat rare diseases, which are poised to represent more than one-fifth of pharmaceutical expenditures by 2022. This widespread use has been facilitated by legislative and regulatory incentives in both the United States and abroad, yet US payers and health systems have not yet made a concerted effort to understand whether and how rare diseases require special considerations on their part and how to adapt traditional methods of health technology assessment and economic evaluation to accommodate these situations. In this article, we explore the general ethical dilemmas that rare diseases present, steps taken by health technology assessment bodies worldwide to define the level of rarity that would necessitate special measures and the modifications to their assessment and valuation processes needed, and the contextual components for rare-disease evaluation that lie outside of the assessment framework as a guide to US decision makers on constructing a formal and relevant process stateside. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. A regulatory perspective on the abuse potential evaluation of novel stimulant drugs in the United States.

    Science.gov (United States)

    Calderon, Silvia N; Klein, Michael

    2014-12-01

    In the United States of America (USA), the abuse potential assessment of a drug is performed as part of the safety evaluation of a drug under development, and to evaluate if the drug needs to be subject to controls that would minimize the abuse of the drug once on the market. The assessment of the abuse potential of new drugs consists of a scientific and medical evaluation of all data related to abuse of the drug. This paper describes the regulatory framework for evaluating the abuse potential of new drugs, in general, including novel stimulants. The role of the United States Food and Drug Administration (FDA) in the evaluation of the abuse potential of drugs, and its role in drug control are also discussed. A definition of abuse potential, an overview of the currently accepted approaches to evaluating the abuse potential of a drug, as well as a description of the criteria that applies when recommending a specific level of control (i.e., a Schedule) for a drug under the Controlled Substances Act (CSA). This article is part of the Special Issue entitled 'CNS Stimulants'. Published by Elsevier Ltd.

  10. Monitoring of drug intake during pregnancy by questionnaires and LC-MS/MS drug urine screening: evaluation of both monitoring methods.

    Science.gov (United States)

    Hoeke, Henrike; Roeder, Stefan; Bertsche, Thilo; Lehmann, Irina; Borte, Michael; von Bergen, Martin; Wissenbach, Dirk K

    2015-08-01

    Various studies pointed towards a relationship between chronic diseases such as asthma and allergy and environmental risk factors, which are one aspect of the so-called Exposome. These environmental risk factors include also the intake of drugs. One critical step in human development is the prenatal period, in which exposures might have critical impact on the child's health outcome. Thereby, the health effects of drugs taken during gestation are discussed controversially with regard to newborns' disease risk. Due to this, the drug intake of pregnant women in the third trimester was monitored by questionnaire, in addition to biomonitoring using a local birth cohort study, allowing correlations of drug exposure with disease risk. Therefore, 622 urine samples were analyzed by an untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) urine screening and the results were compared to self-administered questionnaires. In total, 48% (n = 296) reported an intake of pharmaceuticals, with analgesics as the most frequent reported drug class in addition to dietary supplements. 182 times compounds were detected by urine screening, with analgesics (42%; n = 66) as the predominantly drug class. A comparison of reported and detected drug intake was performed for three different time spans between completion of the questionnaires and urine sampling. Even if the level of accordance was low in general, similar percentages (~25%, ~19%, and ~ 20%) were found for all groups. This study illustrates that a comprehensive evaluation of drug intake is neither achieved by questionnaires nor by biomonitoring alone. Instead, a combination of both monitoring methods, providing complementary information, should be considered. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Lemongrass essential oil gel as a local drug delivery agent for the treatment of periodontitis

    Directory of Open Access Journals (Sweden)

    Shivaraj B Warad

    2013-01-01

    Full Text Available Background: It has been long recognized that periodontal diseases are infections of the periodontium, comprising the bacterial etiology, an immune response, and tissue destruction. Treatment strategies aiming primarily at suppressing or eliminating specific periodontal pathogens include adjunct use of local and systemic antibiotics as part of nonsurgical periodontal therapy. Unwanted side effects and resistance of microorganisms toward antibiotics due to their widespread use have modified the general perception about their efficacy. Research in phytosciences has revealed various medicinal plants offering a new choice of optional antimicrobial therapy. Cymbopogon citratus, Stapf. (lemongrass is a popular medicinal plant. At a concentration ≤2%, lemongrass essential oil inhibits the growth of several kinds of microorganisms including periodontal pathogens, especially the reference strains Actinomyces naeslundii and Porphyromonas gingivalis, which were resistant to tetracycline hydrochloride. Aims: To evaluate the efficacy of locally delivered 2% lemongrass essential oil in gel form as an adjunct to scaling and root planing, as compared to scaling and root planing alone for the treatment of chronic periodontitis. Materials and Methods: 2% Lemongrass essential oil gel was prepared and placed in moderate to deep periodontal pockets after scaling and root planing. Results: Statistically significant reduction in probing depth and gingival index and gain in relative attachment level were noted in the experimental group as compared to the control group at 1 and 3 months. Conclusion: Locally delivered 2% lemongrass essential oil gel offers a new choice of safe and effective adjunct to scaling and root planing in periodontal therapy.

  12. Lemongrass essential oil gel as a local drug delivery agent for the treatment of periodontitis

    Science.gov (United States)

    Warad, Shivaraj B.; Kolar, Sahana S.; Kalburgi, Veena; Kalburgi, Nagaraj B.

    2013-01-01

    Background: It has been long recognized that periodontal diseases are infections of the periodontium, comprising the bacterial etiology, an immune response, and tissue destruction. Treatment strategies aiming primarily at suppressing or eliminating specific periodontal pathogens include adjunct use of local and systemic antibiotics as part of nonsurgical periodontal therapy. Unwanted side effects and resistance of microorganisms toward antibiotics due to their widespread use have modified the general perception about their efficacy. Research in phytosciences has revealed various medicinal plants offering a new choice of optional antimicrobial therapy. Cymbopogon citratus, Stapf. (lemongrass) is a popular medicinal plant. At a concentration ≤2%, lemongrass essential oil inhibits the growth of several kinds of microorganisms including periodontal pathogens, especially the reference strains Actinomyces naeslundii and Porphyromonas gingivalis, which were resistant to tetracycline hydrochloride. Aims: To evaluate the efficacy of locally delivered 2% lemongrass essential oil in gel form as an adjunct to scaling and root planing, as compared to scaling and root planing alone for the treatment of chronic periodontitis. Materials and Methods: 2% Lemongrass essential oil gel was prepared and placed in moderate to deep periodontal pockets after scaling and root planing. Results: Statistically significant reduction in probing depth and gingival index and gain in relative attachment level were noted in the experimental group as compared to the control group at 1 and 3 months. Conclusion: Locally delivered 2% lemongrass essential oil gel offers a new choice of safe and effective adjunct to scaling and root planing in periodontal therapy. PMID:24991068

  13. Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization.

    Science.gov (United States)

    Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

    2015-01-01

    Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

  14. Drug user organizations in the Nordic countries--local, national, and international dimensions.

    Science.gov (United States)

    Frank, Vibeke Asmussen; Anker, Jørgen; Tammi, Tuukka

    2012-04-01

    The article focuses on drug user organizations that represent and advocate for active "hard drug" users in the Nordic countries. It discusses the opportunities and challenges that these organizations face in their search for legitimacy and political influence. The comparative perspective points at similarities and differences in national contexts that both support and challenges the existence of drug user organizations, including drug policy, social welfare policy, trends in drug use, and organizational conditions. The article also discusses the importance of international network and transnational organizations that support drug user organizations.

  15. Pharmaceutical evaluation of different shampoo brands in local Saudi market.

    Science.gov (United States)

    AlQuadeib, Bushra T; Eltahir, Eram K D; Banafa, Rana A; Al-Hadhairi, Lama A

    2018-01-01

    Shampooing is the most common form of hair treatment. Shampoos are primarily products aimed at cleansing the hair and scalp. There are many brands of shampoos in Saudi Arabia, available from different sources, locally and imported from other countries. This study aims to investigate whether such brands comply with the Saudi standard specifications for shampoos, issued by the National Center for Specifications and Standards, and to what extent these specifications are applied. Six shampoo brands were randomly collected from Riyadh market (Pantene®, Sunsilk®, Herbal essences®, Garnier Ultra Doux®, Syoss® and L'Oreal Elvive®). The selected shampoos were evaluated according to their physicochemical properties, including organoleptic characterization, pH measurement, percentage of solid content, rheological measurements, dirt dispersion level, foaming ability and foam stability, and surface tension. All shampoos had a good percentage of solids, excellent foam formation with stable foam and a highly viscous nature. Regarding the pH measurement, all shampoo samples were within the specified range with good wetting ability.

  16. [Improvement of local lymph node assay for cosmetics safety evaluation].

    Science.gov (United States)

    Liu, Zhen; Liu, Junping; Wang, Fei; Xu, Guifeng; Hou, Juan; Wan, Xuying; Zhang, Tianbao

    2009-09-01

    To improve the local lymph node assay (LLNA) as an alternative method to detect chemicals for both sensitization and irritation. The following chemicals: one negative control: 4-Aminobenzoic Acid, three sensitizers: 2,4-dinitrochlorobenzene (DNCB), Hexyl cinnamic aldehyde (HCA), 2-Aminophenol (2-APC) and two irritations: potassium hydroxide (KOH), sodium lauryl sulphate (SLS) were selected. According to the normal LLNA, groups of female Balb/c mice were treated with test solutions. The thickness of each ear was measured and each auricle was weighed. On the sixth day, the bilateral draining auricular lymph nodes were excised and weighed. The single cell suspensions were prepared, the lymphocyte were counted and the proliferations of lymph cells were detected by cell counting kit-8 (CCK-8). Significant increase in ear thickness and weight were found in groups of KOH, SLS and DNCB (above 0.5%) (P LLNA using auricle thickness and weighing as observed markers for irritation, and using lymph nodes weighing and proliferation of lymphocyte as observed markers for sensitization, could evaluate both sensitization and irritation at the same time.

  17. Review of regulatory recommendations for orphan drug submissions in the Netherlands and Scotland : focus on the underlying pharmacoeconomic evaluations

    NARCIS (Netherlands)

    Vegter, Stefan; Rozenbaum, Mark H.; Postema, Roelien; Tolley, Keith; Postma, Maarten J.

    2010-01-01

    Background: Pharmacoeconomic evaluations of new drug therapies are often required for reimbursement or guidance decisions. However, for orphan drugs, country-specific requirements exist. In the Netherlands, orphan drug developers can be exempted from providing a full pharmacoeconomic evaluation,

  18. Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery.

    Science.gov (United States)

    Dai, Min; Wu, Cong; Fang, Hong-Ming; Li, Li; Yan, Jia-Bao; Zeng, Dan-Lin; Zou, Tao

    2017-06-01

    We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210 nm and -14 mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12 nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.

  19. Evaluation of a model training program for respiratory-protection preparedness at local health departments.

    Science.gov (United States)

    Alfano-Sobsey, Edie; Kennedy, Bobby; Beck, Frank; Combs, Brian; Kady, Wendy; Ramsey, Steven; Stockweather, Allison; Service, Will

    2006-04-01

    Respiratory-protection programs have had limited application in local health departments and have mostly focused on protecting employees against exposure to tuberculosis (TB). The need to provide the public health workforce with effective respiratory protection has, however, been underscored by recent concerns about emerging infectious diseases, bioterrorism attacks, drug-resistant microbes, and environmental exposures to microbial allergens (as in recent hurricane flood waters). Furthermore, OSHA has revoked the TB standard traditionally followed by local health departments, replacing it with a more stringent regulation. The additional OSHA requirements may place increased burdens on health departments with limited resources and time. For these reasons, the North Carolina Office of Public Health Preparedness and Response and industrial hygienists of the Public Health Regional Surveillance Teams have developed a training program to facilitate implementation of respiratory protection programs at local health departments. To date, more than 1,400 North Carolina health department employees have been properly fit-tested for respirator use and have received training in all aspects of respiratory protection. This article gives an overview of the development and evaluation of the program. The training approach presented here can serve as a model that other health departments and organizations can use in implementing similar respiratory-protection programs.

  20. [Significance of re-evaluation and development of Chinese herbal drugs].

    Science.gov (United States)

    Gao, Yue; Ma, Zengchun; Zhang, Boli

    2012-01-01

    The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

  1. Prevalence of hypersensitivity to dental local anesthetic drugs in patients referred to Tehran Allergy clinic (2005-2007

    Directory of Open Access Journals (Sweden)

    Akhlaghi F.

    2009-03-01

    Full Text Available "nBackground and Aim: According to controversies in the prevalence of hypersensitivity to dental local anesthetic drugs and patients who claim hypersensitivity to these drugs, the aim of this study was to determine the prevalence of hypersensitivity to dental amide local anesthetic drugs in patients referred to Tehran Allergy Clinic in 2005-2007. "nMaterials and Methods: In this Study (Review of existing data, records of 130 patients who were referred to "Tehran allergy Clinic" (2005-2007 were studied. "nResults: The average age of patients was 29.5±18.8 years. 34% of cases showed positive skin reactions to at least one of the tested Lidocain concentrations and 10% of cases showed positive skin reactions to at least one of the tested Prilocain concentrations. There was a statistically significant difference in hypersensitivity to Lidocain 0.01 and 0.001 (p=0.017 and also between Lidocain 0.001 and 0.0001 (p<0.01. There was no statistically significant difference between other tested drug concentrations (p>0.05. "nConclusion: Many patients with history of hypersensitivity, show positive reaction to local dental anesthetic drugs. Prilocain hypersensitivity reactions are less than Lidocain. So application of Prilocain accompanies with less risk but its application should not be considered completely safe.

  2. Acanthamoeba: epidimiology, pathogenicity and evaluation of effectiveness of recent drugs

    International Nuclear Information System (INIS)

    Issa, R.M.

    2007-01-01

    To study the epidimiology of Acanthamoeba and to evaluate the effectiveness of some recent drugs against parasite. The study was carried out from March to May 2005 at the ophthalmic clinic of King Fahad Hospital, Saudi Arabia. Samples of rinsing solutions and saline of contact lens, tap water, Swimming pool water and Soil from Hufof city Saudi Arabia were tested. Mice were used to infect them via intranasal inoculation from isolated culture strain for confirming pathogenicity. Rokitamycin, polymixin B, suramin and chloropromazin were used to study their effects on Acanthamoeba growth in vitro. Acanthamoeba were detected in 20% of solution of contact lens, 20% of tap water, 50% of swimming pool samples and 40% of soil samples. All animals died or were sacrificed and had Acanthamoeba isolated from their organs. Higher percentage of growth inhibition of Acanthamoeba cultured was shown by chloropromazine and rokitamycin after 21 days (100%), while Polymyin B and Suramin showed 83% and 64% inhibition respectively. Acanthamoeba isolated in significant percent of environmental sources. Pathogenicity of organism was confirmed in mice. Contact lens wearers should be aware of the risks associated with Acanthamoeba. Rokitamycin and chlorpromazine showed good inhibition in vitro. (author)

  3. Evaluation of expansile nanoparticle tumor localization and efficacy in a cancer stem cell-derived model of pancreatic peritoneal carcinomatosis

    Science.gov (United States)

    Herrera, Victoria LM; Colby, Aaron H; Tan, Glaiza AL; Moran, Ann M; O’Brien, Michael J; Colson, Yolonda L; Ruiz-Opazo, Nelson; Grinstaff, Mark W

    2016-01-01

    Aim: To evaluate the tumor localization and efficacy pH-responsive expansile nanoparticles (eNPs) as a drug delivery system for pancreatic peritoneal carcinomatosis (PPC) modeled in nude rats. Methods & materials: A Panc-1-cancer stem cell xeno1graft model of PPC was validated in vitro and in vivo. Tumor localization was tracked via in situ imaging of fluorescent eNPs. Survival of animals treated with paclitaxel-loaded eNPs (PTX-eNPs) was evaluated in vivo. Results: The Panc-1-cancer stem cell xenograft model recapitulates significant features of PPC. Rhodamine-labeled eNPs demonstrate tumor-specific, dose- and time-dependent localization to macro- and microscopic tumors following intraperitoneal injection. PTX-eNPs are as effective as free PTX in treating established PPC; but, PTX-eNPs result in fewer side effects. Conclusion: eNPs are a promising tool for the detection and treatment of PPC. PMID:27078118

  4. 21 CFR 201.200 - Disclosure of drug efficacy study evaluations in labeling and advertising.

    Science.gov (United States)

    2010-04-01

    ... labeling and advertising. 201.200 Section 201.200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Efficacy Study § 201.200 Disclosure of drug efficacy study evaluations in labeling and advertising. (a)(1... bringing to the attention of the prescribers of prescription items the conclusions of the expert panels...

  5. 76 FR 72422 - Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food...

    Science.gov (United States)

    2011-11-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0784] Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  6. Evaluation of the conservative treatment of Trigger finger by local instillation of corticosteroids

    Directory of Open Access Journals (Sweden)

    Muris Pecar

    2011-12-01

    Full Text Available Introduction: Trigger Finger (tenosynovitis stenosans is a specific, named disease from a group of repetitive strain injury (RSI diseases, caused by inflammation which results in difficulties during muscle contraction and weakened and painful tendon movement. It is common in the outpatient physical medicine and rehabilitation practice. The aim of our study was to evaluate the success of conservative treatment of Trigger Finger by local instillation of corticosteroids.Methods: The study was designed as an observational and open analysis of the results of conservative treatment of 45 patients. We used precise instillation of steroid anti-inflammatory antirheumatic drugs in the area of patho-anatomic, microtraumatic injuries of tendon and its sheath. Patients were evaluated before and after the treatment with 0 to 5 evaluation score scale. The data were analyzed using X2 test.Results: Most of the patients had evaluation score of 2, 3 and 4, before the treatment. After the treatment 10 (29% patients had achieved score 4 and 35 (71% patients had achieved score 5. All of the patients with score 5 had excellent working ability with full working capacity. Other patients had well-preserved working ability, which improved to excellent in maximum of 7 days.Conclusions: Conservative treatment of Trigger finger shows good therapeutic effects and taking into account the benefits, convenience and generally lower cost of conservative treatment for the patient, should be considered as an effective alternative to surgical treatment.

  7. 78 FR 8446 - Center for Drug Evaluation and Research; Prescription Drug Labeling Improvement and Enhancement...

    Science.gov (United States)

    2013-02-06

    ... utility of the prescription drug labeling as a communication tool and to discuss strategies for making it... the Web site after this document publishes in the Federal Register.) All holders of marketing... before June 30, 2001, and for generic drugs. The initiative is anticipated to take place over several...

  8. Evaluation of drug administration errors in a teaching hospital

    Directory of Open Access Journals (Sweden)

    Berdot Sarah

    2012-03-01

    Full Text Available Abstract Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds. A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. Results Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors with one or more errors were detected (27.6%. There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501. The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%. The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission. In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC and the number of patient under the nurse's care. Conclusion Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.

  9. Analysis of clinical records of dental patients attending Jordan University Hospital: Documentation of drug prescriptions and local anesthetic injections

    Directory of Open Access Journals (Sweden)

    Najla Dar-Odeh

    2008-08-01

    Full Text Available Najla Dar-Odeh1, Soukaina Ryalat1, Mohammad Shayyab1, Osama Abu-Hammad21Department of Oral and Maxillofacial Surgery Oral Medicine and Periodontics, Faculty of Dentistry, University of Jordan, Jordan; 2Department of Prosthetic Dentistry, Faculty of Dentistry, University of Jordan, JordanObjectives: The aim of this study was to analyze clinical records of dental patients attending the Dental Department at the University of Jordan Hospital: a teaching hospital in Jordan. Analysis aimed at determining whether dental specialists properly documented the drug prescriptions and local anesthetic injections given to their patients.Methods: Dental records of the Dental Department at the Jordan University Hospital were reviewed during the period from April 3rd until April 26th 2007 along with the issued prescriptions during that period.Results: A total of 1000 records were reviewed with a total of 53 prescriptions issued during that period. Thirty records documented the prescription by stating the category of the prescribed drug. Only 13 records stated the generic or the trade names of the prescribed drugs. Of these, 5 records contained the full elements of a prescription. As for local anesthetic injections, the term “LA used” was found in 22 records while the names and quantities of the local anesthetics used were documented in only 13 records. Only 5 records documented the full elements of a local anesthetic injection.Conclusion: The essential data of drug prescriptions and local anesthetic injections were poorly documented by the investigated group of dental specialists. It is recommended that the administration of the hospital and the dental department implement clear and firm guidelines for dental practitioners in particular to do the required documentation procedure.Keywords: dental records, documentation, prescriptions, local anesthesia

  10. Enhancing Macrophage Drug Delivery Efficiency via Co-Localization of Cells and Drug-Loaded Microcarriers in 3D Resonant Ultrasound Field.

    Science.gov (United States)

    Lee, Yu-Hsiang; Wu, Zhen-Yu

    2015-01-01

    In this study, a novel synthetic 3D molecular transfer system which involved the use of model drug calcein-AM-encapsulated poly(lactic-co-glycolic acid) microspheres (CAPMs) and resonant ultrasound field (RUF) with frequency of 1 MHz and output intensity of 0.5 W/cm2 for macrophage drug delivery was explored. We hypothesized that the efficiency of CAPMs-mediated drug delivery aided by RUF can be promoted by increasing the contact opportunities between cells and the micrometer-sized drug carriers due to effects of acoustic radiation forces generated by RUF. Through the fluoromicroscopic and flow cytometric analyses, our results showed that both DH82 macrophages and CAPMs can be quickly brought to acoustic pressure nodes within 20 sec under RUF exposure, and were consequently aggregated throughout the time course. The efficacy of cellular uptake of CAPMs was enhanced with increased RUF exposure time where a 3-fold augmentation (P CAPM delivery efficiency was mainly contributed by the co-localization of cells and CAPMs resulting from the application of the RUF, rather than from sonoporation. In summary, the developed molecular delivery approach provides a feasible means for macrophage drug delivery.

  11. Analysis of wastewater as a new approach to determine the amount of drugs intake by local communities. A review

    Directory of Open Access Journals (Sweden)

    Marta Boroń

    2014-09-01

    Full Text Available Qualitative and quantitative analysis of wastewater in terms of the amount of illegal drugs and their metabolites is a modern method of research, which is considered to be an objective and effective way to determine the amount of substances taken and excreted by humans. The results obtained in a real time allow for a quick identification of the quantitative and qualitative changes of the drugs intake. Such approach allows to estimate the daily intake of the drug by the local communities in terms of cities, countries and even the continent. Most often the estimation refers to the intake of the following drugs: cocaine, amphetamine, methamphetamine, ecstasy and cannabis. The wastewater`s monitoring provides information on the dynamics of the drug level changes depending on the weekday, and the general trend in a year. Retrospective estimation of drug intake carries errors, dependent from sampling, sewer system tightness, the stability of the analytes and mixtures of the wastewater itself but remains objective by providing very valuable information for the institutions struggling with drug crime.

  12. Hepatic transporter drug-drug interactions: an evaluation of approaches and methodologies.

    Science.gov (United States)

    Williamson, Beth; Riley, Robert J

    2017-12-01

    Drug-drug interactions (DDIs) continue to account for 5% of hospital admissions and therefore remain a major regulatory concern. Effective, quantitative prediction of DDIs will reduce unexpected clinical findings and encourage projects to frontload DDI investigations rather than concentrating on risk management ('manage the baggage') later in drug development. A key challenge in DDI prediction is the discrepancies between reported models. Areas covered: The current synopsis focuses on four recent influential publications on hepatic drug transporter DDIs using static models that tackle interactions with individual transporters and in combination with other drug transporters and metabolising enzymes. These models vary in their assumptions (including input parameters), transparency, reproducibility and complexity. In this review, these facets are compared and contrasted with recommendations made as to their application. Expert opinion: Over the past decade, static models have evolved from simple [I]/k i models to incorporate victim and perpetrator disposition mechanisms including the absorption rate constant, the fraction of the drug metabolised/eliminated and/or clearance concepts. Nonetheless, models that comprise additional parameters and complexity do not necessarily out-perform simpler models with fewer inputs. Further, consideration of the property space to exploit some drug target classes has also highlighted the fine balance required between frontloading and back-loading studies to design out or 'manage the baggage'.

  13. The political and scientific challenges in evaluating compulsory drug treatment centers in Southeast Asia.

    Science.gov (United States)

    Vuong, Thu; Nguyen, Nhu; Le, Giang; Shanahan, Marian; Ali, Robert; Ritter, Alison

    2017-01-11

    In Vietnam, like many countries in Southeast Asia, the commonly used approach of center-based compulsory drug treatment (CCT) has been criticized on human rights ground. Meanwhile, community-based voluntary methadone maintenance treatment (MMT) has been implemented for nearly a decade with promising results. Reform-minded leaders have been seeking empirical evidence of the costs and effectiveness associated with these two main treatment modalities. Conducting evaluations of these treatments, especially where randomization is not ethical, presents challenges. The aim of this paper is to discuss political challenges and methodological issues when conducting cost-effectiveness studies within the context of a non-democratic Southeast Asian country. A retrospective analysis of the political and scientific challenges that were experienced in the study design, sample size determination, government approval and ethics approvals, participant recruitment, data collection, and determination of sources, and quantification of cost and effectiveness data was undertaken. As a consequence of the non-randomized design, analysis of patient characteristics for both treatment types was undertaken to identify the magnitude of baseline group differences. Concordance between self-reported heroin use and urine drug testing was undertaken to determine the reliability of self-report data in a politically challenging environment. We demonstrate that conducting research around compulsory treatment in a non-democratic society is feasible, yet it is politically challenging and requires navigation between science and politics. We also demonstrate that engagement with the government decision makers in the research conception, implementation, and dissemination of the results increases the likelihood of research evidence being considered for change in a contentious drug policy area. Local empirical evidence on the comparative cost-effectiveness of CCT and MMT in a Southeast Asian setting is

  14. Evaluating drug prices, availability, affordability, and price components: implications for access to drugs in Malaysia.

    Science.gov (United States)

    Babar, Zaheer Ud Din; Ibrahim, Mohamed Izham Mohamed; Singh, Harpal; Bukahri, Nadeem Irfan; Creese, Andrew

    2007-03-27

    Malaysia's stable health care system is facing challenges with increasing medicine costs. To investigate these issues a survey was carried out to evaluate medicine prices, availability, affordability, and the structure of price components. The methodology developed by the World Health Organization (WHO) and Health Action International (HAI) was used. Price and availability data for 48 medicines was collected from 20 public sector facilities, 32 private sector retail pharmacies and 20 dispensing doctors in four geographical regions of West Malaysia. Medicine prices were compared with international reference prices (IRPs) to obtain a median price ratio. The daily wage of the lowest paid unskilled government worker was used to gauge the affordability of medicines. Price component data were collected throughout the supply chain, and markups, taxes, and other distribution costs were identified. In private pharmacies, innovator brand (IB) prices were 16 times higher than the IRPs, while generics were 6.6 times higher. In dispensing doctor clinics, the figures were 15 times higher for innovator brands and 7.5 for generics. Dispensing doctors applied high markups of 50%-76% for IBs, and up to 316% for generics. Retail pharmacy markups were also high-25%-38% and 100%-140% for IBs and generics, respectively. In the public sector, where medicines are free, availability was low even for medicines on the National Essential Drugs List. For a month's treatment for peptic ulcer disease and hypertension people have to pay about a week's wages in the private sector. The free market by definition does not control medicine prices, necessitating price monitoring and control mechanisms. Markups for generic products are greater than for IBs. Reducing the base price without controlling markups may increase profits for retailers and dispensing doctors without reducing the price paid by end users. To increase access and affordability, promotion of generic medicines and improved availability

  15. Evaluating drug prices, availability, affordability, and price components: implications for access to drugs in Malaysia.

    Directory of Open Access Journals (Sweden)

    Zaheer Ud Din Babar

    2007-03-01

    Full Text Available BACKGROUND: Malaysia's stable health care system is facing challenges with increasing medicine costs. To investigate these issues a survey was carried out to evaluate medicine prices, availability, affordability, and the structure of price components. METHODS AND FINDINGS: The methodology developed by the World Health Organization (WHO and Health Action International (HAI was used. Price and availability data for 48 medicines was collected from 20 public sector facilities, 32 private sector retail pharmacies and 20 dispensing doctors in four geographical regions of West Malaysia. Medicine prices were compared with international reference prices (IRPs to obtain a median price ratio. The daily wage of the lowest paid unskilled government worker was used to gauge the affordability of medicines. Price component data were collected throughout the supply chain, and markups, taxes, and other distribution costs were identified. In private pharmacies, innovator brand (IB prices were 16 times higher than the IRPs, while generics were 6.6 times higher. In dispensing doctor clinics, the figures were 15 times higher for innovator brands and 7.5 for generics. Dispensing doctors applied high markups of 50%-76% for IBs, and up to 316% for generics. Retail pharmacy markups were also high-25%-38% and 100%-140% for IBs and generics, respectively. In the public sector, where medicines are free, availability was low even for medicines on the National Essential Drugs List. For a month's treatment for peptic ulcer disease and hypertension people have to pay about a week's wages in the private sector. CONCLUSIONS: The free market by definition does not control medicine prices, necessitating price monitoring and control mechanisms. Markups for generic products are greater than for IBs. Reducing the base price without controlling markups may increase profits for retailers and dispensing doctors without reducing the price paid by end users. To increase access and

  16. Evaluating Drug Prices, Availability, Affordability, and Price Components: Implications for Access to Drugs in Malaysia

    Science.gov (United States)

    Babar, Zaheer Ud Din; Ibrahim, Mohamed Izham Mohamed; Singh, Harpal; Bukahri, Nadeem Irfan; Creese, Andrew

    2007-01-01

    Background Malaysia's stable health care system is facing challenges with increasing medicine costs. To investigate these issues a survey was carried out to evaluate medicine prices, availability, affordability, and the structure of price components. Methods and Findings The methodology developed by the World Health Organization (WHO) and Health Action International (HAI) was used. Price and availability data for 48 medicines was collected from 20 public sector facilities, 32 private sector retail pharmacies and 20 dispensing doctors in four geographical regions of West Malaysia. Medicine prices were compared with international reference prices (IRPs) to obtain a median price ratio. The daily wage of the lowest paid unskilled government worker was used to gauge the affordability of medicines. Price component data were collected throughout the supply chain, and markups, taxes, and other distribution costs were identified. In private pharmacies, innovator brand (IB) prices were 16 times higher than the IRPs, while generics were 6.6 times higher. In dispensing doctor clinics, the figures were 15 times higher for innovator brands and 7.5 for generics. Dispensing doctors applied high markups of 50%–76% for IBs, and up to 316% for generics. Retail pharmacy markups were also high—25%–38% and 100%–140% for IBs and generics, respectively. In the public sector, where medicines are free, availability was low even for medicines on the National Essential Drugs List. For a month's treatment for peptic ulcer disease and hypertension people have to pay about a week's wages in the private sector. Conclusions The free market by definition does not control medicine prices, necessitating price monitoring and control mechanisms. Markups for generic products are greater than for IBs. Reducing the base price without controlling markups may increase profits for retailers and dispensing doctors without reducing the price paid by end users. To increase access and affordability

  17. UV-crosslinkable and thermo-responsive chitosan hybrid hydrogel for NIR-triggered localized on-demand drug delivery.

    Science.gov (United States)

    Wang, Lei; Li, Baoqiang; Xu, Feng; Xu, Zheheng; Wei, Daqing; Feng, Yujie; Wang, Yaming; Jia, Dechang; Zhou, Yu

    2017-10-15

    Innovative drug delivery technologies based on smart hydrogels for localized on-demand drug delivery had aroused great interest. To acquire smart UV-crosslinkable chitosan hydrogel for NIR-triggered localized on-demanded drug release, a novel UV-crosslinkable and thermo-responsive chitosan was first designed and synthesized by grafting with poly N-isopropylacrylamide, acetylation of methacryloyl groups and embedding with photothermal carbon. The UV-crosslinkable unit (methacryloyl groups) endowed chitosan with gelation via UV irradiation. The thermo-responsive unit (poly N-isopropylacrylamide) endowed chitosan hydrogel with temperature-triggered volume shrinkage and reversible swelling/de-swelling behavior. The chitosan hybrid hydrogel embedded with photothermal carbon exhibited distinct NIR-triggered volume shrinkage (∼42% shrinkage) in response to temperature elevation as induced by NIR laser irradiation. As a demonstration, doxorubicin release rate was accelerated and approximately 40 times higher than that from non-irradiated hydrogels. The UV-crosslinkable and thermal-responsive hybrid hydrogel served as in situ forming hydrogel-based drug depot is developed for NIR-triggered localized on-demand release. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Physicochemical, nutritive and safety evaluation of local cereal ...

    African Journals Online (AJOL)

    SARAH

    2014-11-30

    Nov 30, 2014 ... practices and good manufacturing processing should be considered. Such initiatives need to be carried amongst local cereal producers to help minimize food safety risk and ... potential for contamination and deterioration with.

  19. 5-Fluorouracil Encapsulated Chitosan Nanoparticles for pH-Stimulated Drug Delivery: Evaluation of Controlled Release Kinetics

    Directory of Open Access Journals (Sweden)

    R. Seda Tığlı Aydın

    2012-01-01

    Full Text Available Nanoparticles consisting of human therapeutic drugs are suggested as a promising strategy for targeted and localized drug delivery to tumor cells. In this study, 5-fluorouracil (5-FU encapsulated chitosan nanoparticles were prepared in order to investigate potentials of localized drug delivery for tumor environment due to pH sensitivity of chitosan nanoparticles. Optimization of chitosan and 5-FU encapsulated nanoparticles production revealed 148.8±1.1 nm and 243.1±17.9 nm particle size diameters with narrow size distributions, which are confirmed by scanning electron microscope (SEM images. The challenge was to investigate drug delivery of 5-FU encapsulated chitosan nanoparticles due to varied pH changes. To achieve this objective, pH sensitivity of prepared chitosan nanoparticle was evaluated and results showed a significant swelling response for pH 5 with particle diameter of ∼450 nm. In vitro release studies indicated a controlled and sustained release of 5-FU from chitosan nanoparticles with the release amounts of 29.1–60.8% due to varied pH environments after 408 h of the incubation period. pH sensitivity is confirmed by mathematical modeling of release kinetics since chitosan nanoparticles showed stimuli-induced release. Results suggested that 5-FU encapsulated chitosan nanoparticles can be launched as pH-responsive smart drug delivery agents for possible applications of cancer treatments.

  20. Local anesthetic effects of bupivacaine loaded lipid-polymer hybrid nanoparticles: In vitro and in vivo evaluation.

    Science.gov (United States)

    Ma, Pengju; Li, Ting; Xing, Huaixin; Wang, Suzhen; Sun, Yingui; Sheng, Xiugui; Wang, Kaiguo

    2017-05-01

    There is a compelling need for prolonged local anesthetic that would be used for analgesia with a single administration. However, due to the low molecular weight of local anesthetics (LA) (lidocaine, bupivacaine, procaine, dibucaine, etc), they present fast systemic absorption. The aim of the present study was to develop and evaluate bupivacaine lipid-polymer hybrid nanoparticles (BVC LPNs), and compared with BVC loaded PLGA nanoparticles (BVC NPs). Their morphology, particle size, zeta potential and drug loading capacity were evaluated. In vitro release study, stability and cytotoxicity were studied. In vivo evaluation of anesthetic effects was performed on animal models. A facile nanoprecipitation and self-assembly method was optimized to obtain BVC LPNs, composed of PLGA, lecithin and DSPE-PEG 2000 , of ∼175nm particle size. Compared to BVC NPs, BVC LPNs exhibited prolonged in vitro release in phosphate-buffered saline (pH=7.4). Further, BVC LPNs displayed enhanced in vitro stability in 10% FBS and lower cytotoxicity (the concentration of BVC ranging from 1.0μM to 20μM). In addition, BVC LPNs exhibited significantly prolonged analgesic duration. These results demonstrate that the LPNs could function as promising drug delivery system for overcoming the drawbacks of poor stability and rapid drug leakage, and prolonging the anesthetic effect with slight toxicity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Performance evaluation of packet video transfer over local area networks

    OpenAIRE

    Lu, Jie

    1993-01-01

    This research investigates the implementation and performance of packet video transfer over local area networks. A network architecture is defined for packet video such that most of the processing is performed by the higher layers of the Open Systems Interconnection (OSI) reference model, while the lower layers provide real-time services. Implementation methods are discussed for coding schemes, including data compression, the network interface unit, and the underlying local are...

  2. Drug delivery systems based on biocompatible imino-chitosan hydrogels for local anticancer therapy.

    Science.gov (United States)

    Ailincai, Daniela; Tartau Mititelu, Liliana; Marin, Luminita

    2018-11-01

    A series of drug delivery systems were prepared by chitosan hydrogelation with citral in the presence of an antineoplastic drug: 5-fluorouracil. The dynamic covalent chemistry of the imine linkage allowed the obtaining of supramolecular tridimensional architectures in which the drug has been homogenously dispersed. Fourier-transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WXRD) and polarized light microscopy (POM) measurements were used in order to follow the hydrogelation and drug encapsulation processes. The ability of the prepared systems to release the drug has been investigated by UV-Vis spectroscopy using a calibration curve and by fitting the results with different mathematic models. To mimic the behavior of the hydrogel matrix in bio-environmental conditions in view of applications, their enzymatic degradability was monitored in the presence of lysozyme. The in vivo side effects of the systems, in terms of their influence on the blood elements, biochemical and immune parameters were monitored on white Swiss mice by intraperitoneal administration of the injectable obtained hydrogels. All the characteristics of the obtained systems, such as micro-porous morphology, uniform drug encapsulation, enzymatic degradability, lack of side effects, other than the one of the drug itself, along with their ability to release the drug in a sustained manner proved that these material meet the requirements for the development of drug delivery systems, making them suitable for being applied in intraperitoneal chemotherapy.

  3. The War on Illegal Drug Production and Trafficking: An Economic Evaluation of Plan Colombia

    OpenAIRE

    Daniel Mejía; Pascual Restrepo

    2008-01-01

    This paper provides a thorough economic evaluation of the anti-drug policies implemented in Colombia between 2000 and 2006 under the so-called Plan Colombia. The paper develops a game theory model of the war against illegal drugs in producer countries. We explicitly model illegal drug markets, which allows us to account for the feedback effects between policies and market outcomes that are potentially important when evaluating large scale policy interventions such as Plan Colombia. We use ava...

  4. Rational drug use--evaluation of a training programme for interns.

    Science.gov (United States)

    Natu, M V; Zachariah, P; Zachariah, A; Chand, S; Singh, T; Choudhry, K

    1995-09-01

    A workshop covering various aspects of rational drug use was conducted for interns of Christian Medical College, Ludhiana. Evaluation of the workshop revealed that it was able to bring about an attitudinal change regarding rational drug use. The methodology and evaluation procedures have been described. It is suggested that similar attempts should be made at all medical colleges so that every graduate enters medical practice with a positive attitude towards rational drug use.

  5. Evaluation of drug therapy problems among renal patients receiving ...

    African Journals Online (AJOL)

    Adibe et al. Trop J Pharm Res, March 2017; 16(3): 697 .... suggestions to address medication problems, ..... Preventable drug-related hospital admissions. Ann. Pharmacother. 2002;. 36: .... geriatric hospitalized patients in yogyakarta hospitals,.

  6. Evaluation of Information Contained in Drug Advertisement and ...

    African Journals Online (AJOL)

    This was a descriptive study based on critical appraisal of drug promotional brochures and leaflets. ..... behavior of doctors in a teaching hospital in Ibadan,. Nigeria. ... Guide. Edinburgh, Churchills Living stone, 1999: 111–116. 12. Buck ML.

  7. Evaluation of drug administration errors in a teaching hospital

    OpenAIRE

    Berdot, Sarah; Sabatier, Brigitte; Gillaizeau, Florence; Caruba, Thibaut; Prognon, Patrice; Durieux, Pierre

    2012-01-01

    Abstract Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs...

  8. Evaluation of HIV/AIDS patients' knowledge on antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Regina Flávia de Castro Almeida

    Full Text Available Lack of information on antiretroviral drugs or the misunderstanding of available information can facilitate incorrect use of such drugs. This can result in non-adherence to the prescribed regimen, leading to a great possibility of a therapeutic failure. The aim of this study was to know which information HIV/AIDS patients, who receive their medicines at the pharmacy of a reference hospital in the northeast Brazil, have on the drugs they use, the source of this information and whether there is a need for additional information. A total of 195 HIV/AIDS patients, who were using either zidovudina + lamivudina 300+150mg (AZT+3TC, efavirenz 600mg (EFZ or lopinavir/ritonavir 133.33/33mg (LPV/r, were interviewed. The mean age was 41 years (SD = 9.55 and 70.8% were males. Of the total, 55.4% didn't know the effect of the drug in the organism; 35.9% were unaware of the necessity of taking antiretroviral drugs for the rest of their lives; only 14.4% knew how to proceed when a dosage was missed; 22.1% said they could die and the same number of individuals believed in aggravation of the disease in case of treatment interruption. The majority, 68.2%, considered it very necessary to receive drug information. The results show that there is an apparent lack of general information among users of antiretroviral drugs, and at the same time a need for it. It is necessary that all professionals involved in the health care of the patients agree that an efficient supply of information on prescribed drugs is an ethical component of the treatment that favors and fosters its adherence.

  9. Evaluation procedures for drug crimes, the Iranian legal system

    OpenAIRE

    Mehdi Hariri; Saeid Darougari

    2014-01-01

    Today, drug trafficking, transnational organized crime of, comes into account. Distributors and consumers of drugs, distribution and consumption gradually, the traditional process lubricants Battalion (mechanical and chemical), and this would have altered, requires the development of formal and substantial rights.  The law of success in fighting crime, completely dependent on the integrity, transparency and efficiency of criminal procedure, and the amount of punishment that fits the crime app...

  10. Evaluating local benefits from conservation in Nepal's Annapurna Conservation Area.

    Science.gov (United States)

    Spiteri, Arian; Nepal, Sanjay K

    2008-09-01

    Protected areas are integral to the global effort to conserve biodiversity, and, over the past two decades, protected area managers have begun to recognize that conservation objectives are next to impossible to achieve without considering the needs and concerns of local communities. Incentive-based programs (IBPs) have become a favored approach to protected area management, geared at fostering local stewardship by delivering benefits tied to conservation to local people. Effective IBPs require benefits to accrue to and be recognized by those experiencing the greatest consequences as a result of the protected area, and those likely to continue extractive activities if their livelihood needs are compromised. This research examines dispersal of IBP benefits, as perceived by local residents in Nepal's Annapurna Conservation Area. Results reported here are based on questionnaire interviews with 188 households conducted between September and December 2004. Results indicate that local residents primarily identify benefits from social development activities, provisions for resource extraction, and economic opportunities. Overall, benefits have been dispersed equally to households in villages on and off the main tourist route, and regardless of a household's participation in tourism. However, benefits are not effectively targeted to poorer residents, those highly dependent on natural resources, and those experiencing the most crop damage and livestock loss from protected wildlife. This article provides several suggestions for improving the delivery of conservation incentives.

  11. Automated applications of sandwich-cultured hepatocytes in the evaluation of hepatic drug transport.

    Science.gov (United States)

    Perry, Cassandra H; Smith, William R; St Claire, Robert L; Brouwer, Kenneth R

    2011-04-01

    Predictions of the absorption, distribution, metabolism, excretion, and toxicity of compounds in pharmaceutical development are essential aspects of the drug discovery process. B-CLEAR is an in vitro system that uses sandwich-cultured hepatocytes to evaluate and predict in vivo hepatobiliary disposition (hepatic uptake, biliary excretion, and biliary clearance), transporter-based hepatic drug-drug interactions, and potential drug-induced hepatotoxicity. Automation of predictive technologies is an advantageous and preferred format in drug discovery. In this study, manual and automated studies are investigated and equivalence is demonstrated. In addition, automated applications using model probe substrates and inhibitors to assess the cholestatic potential of drugs and evaluate hepatic drug transport are examined. The successful automation of this technology provides a more reproducible and less labor-intensive approach, reducing potential operator error in complex studies and facilitating technology transfer.

  12. Near-infrared induced release for localized on-demand drug delivery

    NARCIS (Netherlands)

    Vertommen, M.A.M.E.

    2009-01-01

    By non-invasive external triggering of drug release from an implant, pulsewise administration can be realized according to the patient’s needs and at specific locations in the human body. In comparison to more traditional delivery forms (e.g. oral or by injection), externally triggered drug release

  13. Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design

    Science.gov (United States)

    Ishikawa, Toshihisa; Tamura, Ai; Saito, Hikaru; Wakabayashi, Kanako; Nakagawa, Hiroshi

    2005-10-01

    In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

  14. Pooling, meta-analysis, and the evaluation of drug safety

    Directory of Open Access Journals (Sweden)

    Leizorovicz Alain

    2002-03-01

    Full Text Available Abstract Background The "integrated safety report" of the drug registration files submitted to health authorities usually summarizes the rates of adverse events observed for a new drug, placebo or active control drugs by pooling the safety data across the trials. Pooling consists of adding the numbers of events observed in a given treatment group across the trials and dividing the results by the total number of patients included in this group. Because it considers treatment groups rather than studies, pooling ignores validity of the comparisons and is subject to a particular kind of bias, termed "Simpson's paradox." In contrast, meta-analysis and other stratified analyses are less susceptible to bias. Methods We use a hypothetical, but not atypical, application to demonstrate that the results of a meta-analysis can differ greatly from those obtained by pooling the same data. In our hypothetical model, a new drug is compared to 1 a placebo in 4 relatively small trials in patients at high risk for a certain adverse event and 2 an active reference drug in 2 larger trials of patients at low risk for this event. Results Using meta-analysis, the relative risk of experiencing the adverse event with the new drug was 1.78 (95% confidence interval [1.02; 3.12] compared to placebo and 2.20 [0.76; 6.32] compared to active control. By pooling the data, the results were, respectively, 1.00 [0.59; 1.70] and 5.20 [2.07; 13.08]. Conclusions Because these findings could mislead health authorities and doctors, regulatory agencies should require meta-analyses or stratified analyses of safety data in drug registration files.

  15. Polylysine as a vehicle for extracellular matrix-targeted local drug delivery, providing high accumulation and long-term retention within the vascular wall

    NARCIS (Netherlands)

    Sakharov, D.V.; Jie, A.F.H.; Bekkers, M.E.A.; Emeis, J.J.; Rijken, D.C.

    2001-01-01

    We present the first steps in the elaboration of an approach of extracellular matrix-targeted local drug delivery (ECM-LDD), designed to provide a high concentration, ubiquitous distribution, and long-term retention of a drug within the vessel wall after local intravascular delivery. The approach is

  16. Evaluation of the reliability of local farmer knowledge in ...

    African Journals Online (AJOL)

    Abstract:Local farmer knowledge of species distribution patterns and plant palatibality in Namaqualand, South Africa, was assessed using Participatory Rural Appraisal techniques. These findings were compared with the results obtained using phytosociological techniques (species distribution), and with palatability indices ...

  17. Research Note: Evaluation of the reliability of local farmer ...

    African Journals Online (AJOL)

    Abstract:Local farmer knowledge of species distribution patterns and plant palatibality in Namaqualand, South Africa, was assessed using Participatory Rural Appraisal techniques. These findings were compared with the results obtained using phytosociological techniques (species distribution), and with palatability indices ...

  18. Evaluation of local anaesthetic efficacy of the crude extract of ...

    African Journals Online (AJOL)

    ADEYEYE

    Assessment of pain induced by castration in piglets: behavioural and physiologic responses over the subsequent five days. Applied Animal Behaviour Science, 82: 201-. 218. Horn T, Marx G & Borell E (1999). Behaviours of piglets during castration with and without local anaesthesia. Deutsche Tierarztliche. Wochenschrift ...

  19. Tetracycline as local drug delivery in treatment of chronic periodontitis: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Prasad Shyamrajan Nadig

    2016-01-01

    Full Text Available Background: The aim of the present meta-analysis is to determine the efficacy of tetracycline group of antibiotics as local drug delivery agents in the treatment of chronic periodontitis. Materials and Methods: MEDLINE, EBSCO, Cochrane database, and Google Scholar were used to identify studies in English published up to January 31, 2017. An additional hand search of relevant journals and of the bibliographies of the paper identified was also performed. Articles retrieved were screened using specific inclusion criteria by two independent reviewers. Randomized control trials investigating the effect of tetracycline group of antibiotics as local drug delivery agents in chronic periodontitis were included in the study. Results: Ten relevant articles were selected for the meta-analysis, of which five articles were retrieved after electronic search, three articles were included after hand search, and two unpublished articles were included. The number of patients in studies ranged from 13 to 140 sites with mean age ranging from 20 to 75. A total of 588 sites were treated using tetracycline group of antibiotics as local drug delivery agents in the treatment of chronic periodontitis. The meta-analysis showed standard difference in mean −1.02 mm (95% confidence interval [CI] 0.28, 1.75 for clinical gain in attachment in favor of tetracycline group. Standard difference in mean for probing depth (PD was 1.20 mm (95% CI 0.57, 1.87 in tetracycline group. Conclusion: The results of this meta-analysis showed a significant improvement in periodontal parameters such as CAL, PD, and sulcular bleeding index in favor of tetracycline as local drug delivery compared to placebo.

  20. Near-infrared spectroscopy technique to evaluate the effects of drugs in treating traumatic brain edema

    Science.gov (United States)

    Xie, J.; Qian, Z.; Yang, T.; Li, W.; Hu, G.

    2011-01-01

    The aim of this study was to evaluate the effects of several drugs in treating traumatic brain edema (TBE) following traumatic brain injury (TBI) using near-infrared spectroscopy (NIRs) technology. Rats with TBE models were given hypertonic saline (HS), mannitol and mannitol+HS respectively for different groups. Light scattering properties of rat's local cortex was measured by NIRs within the wavelength range from 700 to 850 nm. TBE models were built in rats' left brains. The scattering properties of the right and left target corresponding to the position of normal and TBE tissue were measured and recorded in vivo and real-time by a bifurcated needle probe. The brain water contents (BWC) were measured by the wet and dry weight method after injury and treatment hours 1, 6, 24, 72 and 120. A marked linear relationship was observed between reduced scattering coefficient (μs') and BWC. By recording μs' of rats' brains, the entire progressions of effects of several drugs were observed. The result may suggest that the NIRs techniques have a potential for assessing effects in vivo and real-time on treatment of the brain injury.

  1. Near-infrared spectroscopy technique to evaluate the effects of drugs in treating traumatic brain edema

    Energy Technology Data Exchange (ETDEWEB)

    Xie, J; Qian, Z; Li, W; Hu, G [Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, 29 Yudao Street, Nanjing 210016 (China); Yang, T, E-mail: zhiyu@nuaa.edu.cn [School of Clinical Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China)

    2011-01-01

    The aim of this study was to evaluate the effects of several drugs in treating traumatic brain edema (TBE) following traumatic brain injury (TBI) using near-infrared spectroscopy (NIRs) technology. Rats with TBE models were given hypertonic saline (HS), mannitol and mannitol+HS respectively for different groups. Light scattering properties of rat's local cortex was measured by NIRs within the wavelength range from 700 to 850 nm. TBE models were built in rats' left brains. The scattering properties of the right and left target corresponding to the position of normal and TBE tissue were measured and recorded in vivo and real-time by a bifurcated needle probe. The brain water contents (BWC) were measured by the wet and dry weight method after injury and treatment hours 1, 6, 24, 72 and 120. A marked linear relationship was observed between reduced scattering coefficient ({mu}{sub s}') and BWC. By recording {mu}{sub s}' of rats' brains, the entire progressions of effects of several drugs were observed. The result may suggest that the NIRs techniques have a potential for assessing effects in vivo and real-time on treatment of the brain injury.

  2. Near-infrared spectroscopy technique to evaluate the effects of drugs in treating traumatic brain edema

    International Nuclear Information System (INIS)

    Xie, J; Qian, Z; Li, W; Hu, G; Yang, T

    2011-01-01

    The aim of this study was to evaluate the effects of several drugs in treating traumatic brain edema (TBE) following traumatic brain injury (TBI) using near-infrared spectroscopy (NIRs) technology. Rats with TBE models were given hypertonic saline (HS), mannitol and mannitol+HS respectively for different groups. Light scattering properties of rat's local cortex was measured by NIRs within the wavelength range from 700 to 850 nm. TBE models were built in rats' left brains. The scattering properties of the right and left target corresponding to the position of normal and TBE tissue were measured and recorded in vivo and real-time by a bifurcated needle probe. The brain water contents (BWC) were measured by the wet and dry weight method after injury and treatment hours 1, 6, 24, 72 and 120. A marked linear relationship was observed between reduced scattering coefficient (μ s ') and BWC. By recording μ s ' of rats' brains, the entire progressions of effects of several drugs were observed. The result may suggest that the NIRs techniques have a potential for assessing effects in vivo and real-time on treatment of the brain injury.

  3. Drug resistant Salmonella in broiler chicken sold at local market in ...

    African Journals Online (AJOL)

    user

    2015-10-28

    Oct 28, 2015 ... Key words: Antibiogram, Salmonellosis, PCR, broiler chicken, drug resistance. ... of zoonotic origin and have gained their resistance in an animal host ..... dynamics of Salmonella enterica serotypes in commercial egg and.

  4. Evaluation of Local Government Performance and Presidential Approval in Mexico

    Directory of Open Access Journals (Sweden)

    ALEJANDRA ARMESTO

    2017-01-01

    Full Text Available ¿se benef ician los presidentes del buen desempeño de los gobiernos locales? e ste artículo argu - menta que, en sistemas multinivel donde la claridad de responsabilidades es baja, la aprobación presidencial es afectada por la evaluación ciudadana del desempeño de los gobiernos subnacio - nales. e ste trabajo explora los efectos secundarios del desempeño subnacional en la aprobación presidencial en m éxico, apoyado en datos del estudio del Barómetro de las a méricas efectua - do en 2012. l os resultados de las regresiones logísticas ordinales y regresiones aparentemente no relacionadas indican que la satisfacción con los servicios prestados por los gobiernos locales se asocia positivamente con la aprobación presidencial.

  5. Evaluating the War on Drugs: US and Colombian Interdiction Efforts

    Science.gov (United States)

    1994-03-01

    market remained in the hands of Mexican traffickers.3 When, in the early 1970’s, the US tightened drug enforcement along the border with Mexico and the...US Senate, September 12-13, 1989. Tokatlian, J. , Bagley, B., Eds., Economia y Politica del Narcotraffico, CEI, Bogota, 1990. U.S. Congress. Senate

  6. Evaluation of Herbs as Potential Drugs/Medicines | Odhiambo ...

    African Journals Online (AJOL)

    Herbal drugs have been used since ancient times as medicines for the treatment of a wide range of diseases, for both human and livestock. A study conducted in the Lake Victoria Basin Kenya revealed vast knowledge and reliance on traditional medicine as a source of healthcare. The study documented 34 medicinal plant ...

  7. An Impact Evaluation of a Rural Youth Drug Education Program.

    Science.gov (United States)

    Sarvela, Paul D.; McClendon, E. J.

    1987-01-01

    Examined effects of mixed affective-cognitive drug education program on rural northern Michigan and northeastern Wisconsin sixth and seventh graders' (N=265) substance use health beliefs and behaviors. Alcohol use in this population was determined to be much higher than national average for similar age groups while marijuana, cigarette, and…

  8. Cost and appropriateness of treating asthma with fixed-combination drugs in local health care units in Italy

    Directory of Open Access Journals (Sweden)

    Ruggeri I

    2012-12-01

    Full Text Available Isabella Ruggeri,1 Donatello Bragato,2 Giorgio L Colombo,3,4 Emanuela Valla,3 Sergio Di Matteo41Servizio Governo Area Farmaceutica, Azienda Sanitaria Locale, Milano, Binasco, 2Data Solution Provider, Milan, 3University of Pavia, Department of Drug Sciences, School of Pharmacy, 4Studi Analisi Valutazioni Economiche, MilanBackground: Bronchial asthma is a chronic airways disease and is considered to be one of the major health problems in the Western world. During the last decade, a significant increase in the use of β2-agonists in combination with inhaled corticosteroids has been observed. The aim of this study was to assess the appropriateness of expenditure on these agents in an asthmatic population treated in a real practice setting.Methods: This study used data for a resident population of 635,906 citizens in the integrated patient database (Banca Dati Assistito of a local health care unit (Milano 2 Azienda Sanitaria Locale in the Lombardy region over 3 years (2007–2009. The sample included 3787–4808 patients selected from all citizens aged ≥ 18 years entitled to social security benefits, having a prescription for a corticosteroid + β2-agonist combination, and an ATC code corresponding to R03AK, divided into three groups, ie, pressurized (spray drugs, inhaled powders, and extrafine formulations. Patients with chronic obstructive lung disease were excluded. Indicators of appropriateness were 1–3 packs per year (underdosed, inappropriate, 4–12 packs per year (presumably appropriate, and ≥13 packs per year (overtreatment, inappropriate.Results: The corticosteroid + β2-agonist combination per treated asthmatic patient increased from 37% in 2007 to 45% in 2009 for the total of prescribed antiasthma drugs, and 28%–32% of patients used the drugs in an appropriate manner (4–12 packs per years. The cost of inappropriately used packs increased combination drug expenditure by about 40%, leading to inefficient use of health care

  9. On illicit drug policies; methods of evaluation and comments on recent practices.

    Science.gov (United States)

    Trovato, Giovanni; Vezzani, Antonio

    2013-06-01

    This contribution provides an overview of different approaches used to analyse drug policies within and across countries. Besides the great number of cost of illness studies which have contributed to the assessment of health harms and risks associated to the drug use, most of the recent efforts have focused on the creation of synthetic indices to classify countries around the world or to evaluate particular law enforcement policies in some countries. This is probably due to a general lack of comparable data across countries. The wide variety of budgetary practices in the drugs field in Europe contributes to the problems that exist in estimating drug-related public expenditure. These heterogeneous accounting practices, together with the complexity of the drug phenomenon and the multiplicity of perspectives on the issue, strongly constrains the possibility of economically evaluate and compare drug laws across countries.

  10. Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff

    NARCIS (Netherlands)

    Pires, N.M.M.; Hoeven, B.L. van der; Vries, M.R. de; Havekes, L.M.; Vlijmen, B.J. van; Hennink, W.E.; Quax, P.H.A.; Jukema, J.W.

    2005-01-01

    The introduction of drug-eluting stents (DES) to prevent in-stent restenosis is one of the major advances in interventional cardiology. Currently many types of DES are under evaluation for effectiveness and safety, a time-consuming and difficult procedure in humans. An animal model that allows rapid

  11. [Categories and characteristics of BPH drug evaluation models: a comparative study].

    Science.gov (United States)

    Huang, Dong-Yan; Wu, Jian-Hui; Sun, Zu-Yue

    2014-02-01

    Benign prostatic hyperplasia (BPH) is a worldwide common disease in men over 50 years old, and the exact cause of BPH remains largely unknown. In order to elucidate its pathogenesis and screen effective drugs for the treatment of BPH, many BPH models have been developed at home and abroad. This article presents a comprehensive analysis of the categories and characteristics of BPH drug evaluation models, highlighting the application value of each model, to provide a theoretical basis for the development of BPH drugs.

  12. Drug and Vaccine evaluation in the Human Aotus Plasmodium falciparum Model

    Science.gov (United States)

    2011-05-01

    and phenyl ring systems is anticipated to yield a valuable new antimalarial drug (33). The antimalarial activity and pharmacology of a series of...remains essentially unchanged since 1976, viz. to ascertain the antimalarial activity of drugs against P. falciparum and P. vivax in Aotus. The...Present data on the evaluation of potential antimalarial activity of drugs in the pre-clinical model of Aotus l. lemurinus (Panamanian night

  13. local

    Directory of Open Access Journals (Sweden)

    Abílio Amiguinho

    2005-01-01

    Full Text Available The process of socio-educational territorialisation in rural contexts is the topic of this text. The theme corresponds to a challenge to address it having as main axis of discussion either the problem of social exclusion or that of local development. The reasons to locate the discussion in this last field of analysis are discussed in the first part of the text. Theoretical and political reasons are there articulated because the question is about projects whose intentions and practices call for the political both in the theoretical debate and in the choices that anticipate intervention. From research conducted for several years, I use contributions that aim at discuss and enlighten how school can be a potential locus of local development. Its identification and recognition as local institution (either because of those that work and live in it or because of those that act in the surrounding context are crucial steps to progressively constitute school as a partner for development. The promotion of the local values and roots, the reconstruction of socio-personal and local identities, the production of sociabilities and the equation and solution of shared problems were the dimensions of a socio-educative intervention, markedly globalising. This scenario, as it is argued, was also, intentionally, one of transformation and of deliberate change of school and of the administration of the educative territoires.

  14. Modified local diatomite as potential functional drug carrier--A model study for diclofenac sodium.

    Science.gov (United States)

    Janićijević, Jelena; Krajišnik, Danina; Čalija, Bojan; Vasiljević, Bojana Nedić; Dobričić, Vladimir; Daković, Aleksandra; Antonijević, Milan D; Milić, Jela

    2015-12-30

    Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (∼373mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8h) and those containing physical mixture of the same composition (up to 45% after 8h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Drugs' rapid payoffs distort evaluation of their instrumental uses.

    Science.gov (United States)

    Ainslie, George

    2011-12-01

    Science has needed a dispassionate valuation of psychoactive drugs, but a motivational analysis should be conducted with respect to long-term reward rather than reproductive fitness. Because of hyperbolic overvaluation of short-term rewards, an individual's valuation depends on the time she forms it and the times she will revisit it, sometimes making her best long-term interest lie in total abstinence.

  16. Pharmacognostic and physicochemical evaluation of homoeopathic drug: Erigeron canadensis L.

    Directory of Open Access Journals (Sweden)

    Padma Rao Pogaku

    2017-01-01

    Full Text Available Background: Erigeron canadensis L. is an erect annual herb belonging to the family Asteraceae. Aerial parts are used in Homoeopathy for bruises, cough, dysuria, gonorrhea, haemorrhages, haemorrhoids, spermatorrhea, and wounds. Objective: The pharmacognostic and physicochemical studies have been carried out to facilitate the use of correct species and lay down standards of raw drug materials. Materials and Methods: Pharmacognostic studies of the leaf and stem of authentic samples of E. canadensis L. have been carried out. Physicochemical parameters of the raw drug include extractive values, ash value, and formulation; besides weight per mL, total solids, and alcohol content, high-performance thin layer chromatography (HPTLC and ultraviolet (UV studies are given. Results: Epidermal cells often possess crystals of calcium oxalate. Stomata are anomocytic, anisocytic, and tetracytic types. Trichomes are uniseriate and conical in structure. The mid vein in transection is flat on adaxial and is ribbed toward abaxial, with a secretory cavity beneath the central vascular bundle. Stem in transection is round. The vascular tissue is made of several vascular bundles in a ring. Crystals of calcium oxalate occur in the epidermis, cortex, and pith of stem. In mature stem, secondary xylem is well developed with a reduced phloem. The determined physicochemical data, namely, extractive values, ash values, and preparation of for raw drug and weight per mL, total solids, and alcohol content besides UV and HPTLC profile for finished product are provided. Conclusions: The presented morphoanatomical features along with powder microscopic and organoleptic characters and physicochemical data are diagnostic to establish the standards for ensuring quality and purity of the drug.

  17. Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration.

    Science.gov (United States)

    Cai, Hui; Wen, Xingxing; Wen, Lu; Tirelli, Nicola; Zhang, Xiao; Zhang, Yue; Su, Huanpeng; Yang, Fan; Chen, Gang

    2014-01-01

    In this paper, the potential of poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) for carrying single or compound drugs traversing the round window membrane (RWM) was examined after the round window (RW) administration of different NPs to guinea pigs. First, coumarin-6 was incorporated into PLGA NPs as a fluorescent probe to investigate its ability to cross the RWM. Then, PLGA NPs with salvianolic acid B (Sal B), tanshinone IIA (TS IIA), and total panax notoginsenoside (PNS) including notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Rb1 (Rb1) were developed to evaluate whether NPs loaded with compound drugs would pass through the RWM and improve the local bioavailability of these agents. PLGA NPs loaded with single or compound drugs were prepared by the emulsification solvent evaporation method, and their particle size distribution, particle morphology, and encapsulation efficiency were characterized. In vitro release study showed sustained-release profiles of Sal B, TS IIA, and PNS from the NPs. The pharmacokinetic results showed that NPs applied to the RWM significantly improved drug distribution within the inner ear. The AUC0-t of coumarin-6 in the perilymph (PL) following RW administration of NPs was 4.7-fold higher than that of coumarin-6 solution, and the Cmax was 10.9-fold higher. Furthermore, the AUC(0-t) of R1, Rg1, and Rb1 were 4.0-, 3.1-, and 7.1-fold greater, respectively, after the application of NPs compared to the compound solution, and the Cmax were, respectively, 14.4-, 10.0-, and 16.7-fold higher. These findings suggest that PLGA NPs with unique properties at the nanoscale dimensions have a powerful ability to transport single or compound drugs into the PL through the RWM and remarkably enhance the local bioavailability of the encapsulated drugs in the inner ear. The use of PLGA NPs as nanoscale delivery vehicles to carry drugs across the RWM may be a promising strategy for the treatment of inner ear diseases.

  18. [Drug evaluation in healthy volunteers. Legislative and ethical aspects].

    Science.gov (United States)

    Warot, D

    1991-01-01

    Studies in healthy volunteers have been legalized since December 20th 1988 in France. The healthy volunteer is employed for a variety of studies in phases I and IV of drug development. This type of research can equally be called nontherapeutic in nature. Every experiment involving healthy volunteers should be approved by the Ethics Committee. Using volunteers within the department, company or other organisation, while offering advantages for the investigator should be prohibited as freedom of concept might not be safeguarded. As well, financial incentives may over-persuade individuals, including students, who have low incomes and promote the "professional volunteer". To avoid this problem, French law planned a national register. The potential benefits of such a disposition are still unknown. Having been given appropriate information concerning the drug trial, his obligations and rights, the healthy volunteer gives his written consent. Specific recommendations for nontherapeutic assessments of drug effects are given concerning prisoners, the mentally handicapped, women with a risk of frequency, children. Ethical considerations concerning research on a healthy population must go beyond the law recently promulgated in France.

  19. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities

    Energy Technology Data Exchange (ETDEWEB)

    Kasprzyk-Hordern, Barbara, E-mail: b.kasprzyk-hordern@hud.ac.u [University of Huddersfield, Department of Chemical and Biological Sciences, Queensgate, Huddersfield HD1 3DH (United Kingdom); University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom); Dinsdale, Richard M.; Guwy, Alan J. [University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom)

    2009-06-15

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day{sup -1} 1000 people{sup -1}, which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day{sup -1} 1000 people{sup -1} and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made. - Wastewater as an indicative source of information can be used in forensic applications.

  20. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities

    International Nuclear Information System (INIS)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M.; Guwy, Alan J.

    2009-01-01

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day -1 1000 people -1 , which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day -1 1000 people -1 and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made. - Wastewater as an indicative source of information can be used in forensic applications.

  1. Illicit drugs and pharmaceuticals in the environment--forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2009-06-01

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day(-1) 1000 people(-1), which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day(-1) 1000 people(-1) and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made.

  2. The evaluation of drug regulation - economic approaches into the valuation and evaluation of the drug regulatory framework

    NARCIS (Netherlands)

    Bouvy, J.C.

    2013-01-01

    The European pharmaceutical market is strictly regulated. Sufficient levels of quality, safety, and efficacy will have to be demonstrated before a pharmaceutical is allowed to enter the market. There is little evidence, however, that the current drug regulatory framework is achieving its goals of

  3. In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment.

    Directory of Open Access Journals (Sweden)

    Mareike Hütten

    Full Text Available Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX. To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.

  4. Economic evaluation of diagnostic localization following biochemical prostate cancer recurrence.

    Science.gov (United States)

    Barocas, Daniel A; Bensink, Mark E; Berry, Kristin; Musa, Zahra; Bodnar, Carolyn; Dann, Robert; Ramsey, Scott D

    2014-10-01

    The aim of this study was to assess potential cost-effectiveness of using a prostate cancer specific functional imaging technology capable of identifying residual localized disease versus small volume metastatic disease for asymptomatic men with low but detectable prostate specific antigen (PSA) elevation following radical prostatectomy. Markov modeling was used to estimate the incremental impact on healthcare system costs (2012 USD) and quality-adjusted life-years (QALYs) of two alternative strategies: (i) using the new diagnostic to guide therapy versus (ii) current usual care-using a combination of computed tomography, magnetic resonance imaging, and bone scan to guide therapy. Costs were based on estimates from literature and Medicare reimbursement. Prostate cancer progression, survival, utilities, and background risk of all-cause mortality were obtained from literature. Base-case diagnostic sensitivity (75 percent), specificity (90 percent), and cost (USD 2,500) were provided by our industry partner GE Healthcare. The new diagnostic strategy provided an average gain of 1.83 (95 percent uncertainty interval [UI]: 1.24-2.64) QALYs with added costs of USD 15,595 (95 percent UI: USD -6,330-44,402) over 35 years. The resulting incremental cost-effectiveness ratio was USD 8,516/QALY (95 percent UI: USD -2,947-22,372). RESULTS were most influenced by the utility discounting rate and test performance characteristics; however, the new diagnostic provided clinical benefits over a wide range of sensitivity and specificity. This analysis suggests a diagnostic technology capable of identifying whether men with biochemical recurrence after radical prostatectomy have localized versus metastatic disease would be a cost-effective alternative to current standard work-up. The results support additional investment in development and validation of such a diagnostic.

  5. Maternal drug use: evaluation of risks to breast-fed infants.

    Science.gov (United States)

    Kirksey, A; Groziak, S M

    1984-01-01

    This paper, based on a review of the literature, evaluates the risks to infants of maternal drug use during lactation. The potential harm of a particular drug to the breastfed infant is related both to the complex mechanism of milk synthesis and secretion and the mode of passage of the drug from plasma into milk. The 1st part of the paper discusses mammary cell and milk synthesis, milk secretion and composition, the mode of passage of drugs into milk, and factors influencing drug concentrations in milk. Drug concentrations in milk are dependent on 6 major factors: drug dosage, proportion bound in plasma, molecular weight, lipid solubility, degree of ionization, and pH difference between plasma and milk. Drugs that are weak acids are ionized to a greater extent and are more protein-bound than weak alkaline drugs. The 2nd part of the paper evaluates the risks to breastfed infants of selected pharmacons. Some categories of drugs that contain pharmacons that should be limited or avoided by nursing mothers are alkylating agents, analgesics and anti-inflammatory agents, anticoagulants, anticonvulsants, anti-infective agents, central nervous system stimulants, hormones, laxatives, minerals, provitamins, psychotherapeutic agents, thyroid affecting agents, and vitamins. The following precautions are suggested to minimize the risks of potentially harmful pharmacons: 1) all unnecessary medications should be avoided by nrusing mothers; 2) if medication is necessary during lactation, drug dosage should be controlled and the infant should be monitored for adverse symptoms; 3) drugs should be administered shortly after breastfeeding and the interval prolonged before the next feeding; and 4) if the infant must be fed soon after a potentially harmful drug has been taken by the mother, bottle feeding is recommended.

  6. Controlled local drug delivery strategies from chitosan hydrogels for wound healing.

    Science.gov (United States)

    Elviri, Lisa; Bianchera, Annalisa; Bergonzi, Carlo; Bettini, Ruggero

    2017-07-01

    The main target of tissue engineering is the preparation and application of adequate materials for the design and production of scaffolds, that possess properties promoting cell adhesion, proliferation and differentiation. The use of natural polysaccharides, such as chitosan, to prepare hydrogels for wound healing and controlled drug delivery is a research topic of wide and increasing interest. Areas covered: This review presents the latest results and challenges in the preparation of chitosan and chitosan-based scaffold/hydrogel for wound healing applications. A detailed overview of their behavior in terms of controlled drug delivery, divided by drug categories, and efficacy was provided and critically discussed. Expert opinion: The need to establish and exploit the advantages of natural biomaterials in combination with active compounds is playing a pivotal role in the regenerative medicine fields. The challenges posed by the many variables affecting tissue repair and regeneration need to be standardized and adhere to recognized guidelines to improve the quality of evidence in the wound healing process. Currently, different methodologies are followed to prepare innovative scaffold formulations and structures. Innovative technologies such as 3D printing or bio-electrospray are promising to create chitosan-based scaffolds with finely controlled structures with customizable shape porosity and thickness. Chitosan scaffolds could be designed in combination with a variety of polysaccharides or active compounds with selected and reproducible spacial distribution, providing active wound dressing with highly tunable controlled drug delivery.

  7. Advanced Drug Delivery Systems - a Synthetic and Biological Applied Evaluation

    DEFF Research Database (Denmark)

    Bjerg, Lise Nørkjær

    function as the targeting moiety on the surface of the liposomes. Several examples of synthetic procedures known from the literature are presented. The chapter is completed with a study covering the conjugation efficiencies of a variety of chemical functionalities. Large differences are revealed between...... to guide the uptake, in addition to an enzymatically cleavable peptide sequence, whose cleavage would result in removal of the polymer layer as well as uncovering cationic charges on the liposomal surface. These systems were shown to have superior drug efficacy in vitro....

  8. ULTRACAVITATION METHOD OF EVALUATION IN THE REDUCTION OF LOCALIZED FAT IN WOMEN

    OpenAIRE

    L. Petraglia; D. R. X. O. Crege; J. L. Dullius; A. E. Bighetti

    2017-01-01

    This study evaluated cosmetic fat reduction methods that cause localized lipolysis and that are not invasive. The use of a differentiated ultrasound called Ultracavitation was evaluated, it causes reduction of localized fat in the infra abdominal region. 30 women aged 30-45 years old, healthy, sedentary were evaluated; they were separated into two groups subjected to 12 treatment sessions in infra abdominal region, once a week, alone or combined with aerobic exercise. Photographic recording w...

  9. Effect of liposomes on rheological and syringeability properties of hyaluronic acid hydrogels intended for local injection of drugs.

    Science.gov (United States)

    El Kechai, Naila; Bochot, Amélie; Huang, Nicolas; Nguyen, Yann; Ferrary, Evelyne; Agnely, Florence

    2015-06-20

    The aim of this work was to thoroughly study the effect of liposomes on the rheological and the syringeability properties of hyaluronic acid (HA) hydrogels intended for the local administration of drugs by injection. Whatever the characteristics of the liposomes added (neutral, positively or negatively charged, with a corona of polyethylene glycol chains, size), the viscosity and the elasticity of HA gels increased in a lipid concentration-dependent manner. Indeed, liposomes strengthened the network formed by HA chains due to their interactions with this polymer. The nature and the resulting effects of these interactions depended on liposome composition and concentration. The highest viscosity and elasticity were observed with liposomes covered by polyethylene glycol chains while neutral liposomes displayed the lowest effect. Despite their high viscosity at rest, all the formulations remained easily injectable through needles commonly used for local injections thanks to the shear-thinning behavior of HA gels. The present study demonstrates that rheological and syringeability tests are both necessary to elucidate the behavior of such systems during and post injection. In conclusion, HA liposomal gels appear to be a promising and versatile formulation platform for a wide range of applications in local drug delivery when an injection is required. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Energy Decomposition Analysis Based on Absolutely Localized Molecular Orbitals for Large-Scale Density Functional Theory Calculations in Drug Design.

    Science.gov (United States)

    Phipps, M J S; Fox, T; Tautermann, C S; Skylaris, C-K

    2016-07-12

    We report the development and implementation of an energy decomposition analysis (EDA) scheme in the ONETEP linear-scaling electronic structure package. Our approach is hybrid as it combines the localized molecular orbital EDA (Su, P.; Li, H. J. Chem. Phys., 2009, 131, 014102) and the absolutely localized molecular orbital EDA (Khaliullin, R. Z.; et al. J. Phys. Chem. A, 2007, 111, 8753-8765) to partition the intermolecular interaction energy into chemically distinct components (electrostatic, exchange, correlation, Pauli repulsion, polarization, and charge transfer). Limitations shared in EDA approaches such as the issue of basis set dependence in polarization and charge transfer are discussed, and a remedy to this problem is proposed that exploits the strictly localized property of the ONETEP orbitals. Our method is validated on a range of complexes with interactions relevant to drug design. We demonstrate the capabilities for large-scale calculations with our approach on complexes of thrombin with an inhibitor comprised of up to 4975 atoms. Given the capability of ONETEP for large-scale calculations, such as on entire proteins, we expect that our EDA scheme can be applied in a large range of biomolecular problems, especially in the context of drug design.

  11. An Evaluation of Immediate Outcomes and Fidelity of a Drug Abuse Prevention Program in Continuation High Schools: Project towards No Drug Abuse (TND)

    Science.gov (United States)

    Lisha, Nadra E.; Sun, Ping; Rohrbach, Louise A.; Spruijt-Metz, Donna; Unger, Jennifer B.; Sussman, Steve

    2012-01-01

    The present study provides an implementation fidelity, process, and immediate outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention program targeting continuation high school youth (n = 1426) at risk for drug abuse. A total of 24 schools participated in three randomized conditions: TND Only, TND and motivational…

  12. Clinical evaluation of neoplasms with localized P-31 spectroscopy

    International Nuclear Information System (INIS)

    Charles, H.C.; Sostman, H.D.; Dewhirst, M.W.; Leopold, K.A.; Oleson, J.; Harrelson, J.

    1988-01-01

    Forty integrated P-31 MR spectroscopy and H-1 MR imaging studies were accomplished in eight humans and four dogs with soft-tissue sarcomas on a 1.5-T Signa MR system (General Electric) with the H-1 body coil and a 6-cm diameter P-31 surface coil. Proton MR imaging studies (T1-weighted, T2-weighted, and GRASS) were performed prior to the spectroscopic study. Phosphorus studies (repetition time = 1,500 msec) were acquired with both simple B1 localization and 1D-chemical shift imaging (FOV = 128 cm, no. of views = 128, TX = 12.8 min). Patients were treated with fractionated radiation therapy and radio-frequency hyperthermia over 1 month. Patients underwent definitive resection 3 weeks after completion of radiation therapy, while canines were followed clinically. Of note was significant variation in PCr, PME, Pi, and PDE with spatial location in the tissue. The metabolic profile of these tumors as measured by P-31 spectroscopy altered significantly during therapy

  13. QUALITY GROWTH AND EVALUATION OF PERFORMANCE OF LOCAL PUBLIC SERVICES

    Directory of Open Access Journals (Sweden)

    Remus Gherman

    2015-05-01

    Full Text Available Public sector reform aims to increase performance by improving its efficiency and effectiveness by improving the quality of services provided by public service in order to maximize individual welfare of citizens. The purpose of reform is to improve public services because they have to deal with uncertainties and rapid changes that take place in the internal environmental and external pressures. Public administration, in quality of service provider must make a series of efforts to ensure that citizens know their rights and public services on witch they can benefit taking into account the simplification of service delivery, a high quality of its, new administrative procedures for allocating resources in a transparent way and informing the citizens of standards of services and of the methods of compensation in case if the provided quality is different from that promised. Most important is the fact that the local government must realize that effectiveness involves defining objectives that must be achieved simultaneously with the estimation of the results obtained.

  14. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoguang [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Department of Medical Microbiology, Harbin Medical University, Harbin 150086 (China); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Qian, Hua [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Miyamoto, Fusako [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Naito, Takeshi [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Kawaji, Kumi [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Kajiwara, Kazumi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyo-ku, Kyoto 615-8245 (Japan); Hattori, Toshio [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Matsuoka, Masao [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); and others

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, 'phenotypic drug evaluation', may be applicable for the evaluation of various antiviral drugs in vivo.

  15. Failure mode and fracture behavior evaluation of pipes with local wall thinning subjected to bending load

    International Nuclear Information System (INIS)

    Ahn, Seok Hwan; Nam, Ki Woo; Kim, Seon Jin; Kim, Jin Hwan; Kim, Hyun Soo; Do, Jae Yoon

    2003-01-01

    Fracture behaviors of pipes with local wall thinning are very important for the integrity of nuclear power plant. In pipes of energy plants, sometimes, the local wall thinning may result from severe Erosion-Corrosion (E/C) damage. However, the effects of local wall thinning on strength and fracture behaviors of piping system were not well studied. In this paper, the monotonic bending tests were performed of full-scale carbon steel pipes with local wall thinning. A monotonic bending load was applied to straight pipe specimens by four-point loading at ambient temperature without internal pressure. From the tests, fracture behaviors and fracture strength of locally thinned pipe were manifested systematically. The observed failure modes were divided into four types; ovalization, crack initiation/growth after ovalization, local buckling and crack initiating/growth after local buckling. Also, the strength and the allowable limit of piping system with local wall thinning were evaluated

  16. Soft and flexible poly(ethylene glycol) nanotubes for local drug delivery.

    Science.gov (United States)

    Newland, B; Taplan, C; Pette, D; Friedrichs, J; Steinhart, M; Wang, W; Voit, B; Seib, F P; Werner, C

    2018-05-10

    Nanotubes are emerging as promising materials for healthcare applications but the selection of clinically relevant starting materials for their synthesis remains largely unexplored. Here we present, for the first time, the synthesis of poly(ethylene glycol) (PEG) based nanotubes via the photopolymerization of poly(ethylene glycol) diacrylate and other diacrylate derivatives within the pores of anodized aluminum oxide templates. Template-assisted synthesis allowed the manufacture of a diverse set of polymeric nanotubes with tunable physical characteristics including diameter (∼200-400 nm) and stiffness (405-902 kPa). PEG nanotubes were subjected to cytotoxicty assessment in cell lines and primary stem cells and showed excellent cytocompatability (IC50 > 120 μg ml-1). Nanotubes were readily drug loaded but released the majority of the drug over 5 days. Direct administration of drug loaded nanotubes to human orthotopic breast tumors substantially reduced tumor growth and metastasis and outperformed i.v. administration at the equivalent dose. Overall, this nanotube templating platform is emerging as a facile route for the manufacture of poly(ethylene glycol) nanotubes.

  17. Human skeletal muscle drug transporters determine local exposure and toxicity of statins.

    Science.gov (United States)

    Knauer, Michael J; Urquhart, Bradley L; Meyer zu Schwabedissen, Henriette E; Schwarz, Ute I; Lemke, Christopher J; Leake, Brenda F; Kim, Richard B; Tirona, Rommel G

    2010-02-05

    The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity. We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro. We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1. These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity.

  18. NK-cell activity in immunotoxicity drug evaluation

    International Nuclear Information System (INIS)

    Cederbrant, Karin; Marcusson-Staaahl, Maritha; Condevaux, Fabienne; Descotes, Jacques

    2003-01-01

    NK-cell activity as a tool for detection of immunotoxic effects of new human drugs has gained further attention when the recent European note for guidance CPMP/SWP/1042/99 was adopted. The inclusion of NK-cell activity plus distribution of lymphocyte subsets were suggested as an alternative to the primary antibody response to a T-cell dependent antigen. Either of the two test alternatives should be included as a routine parameter in at least one repeated dose-toxicity study, rats or mice being the species of choice. The standard procedure for measuring NK-cell activity is the 51 Cr-release assay. However, a new flow-cytometric assay, adapted for rat peripheral blood, does not require dedicated groups of animals, offers the possibility of repeated testing, and shows at least as sensitive as the conventional 51 Cr-release assay

  19. Evaluation of Biosourced Alkyd Nanoemulsions as Drug Carriers

    Directory of Open Access Journals (Sweden)

    Siew Yong Teo

    2015-01-01

    Full Text Available Novel oil-in-water (O/W nanoemulsions were formulated using short, medium, and long oil length alkyds synthesized from palm kernel oil by a two-stage alcoholysis-polyesterification reaction. Alkyd/surfactant/water ternary phase diagrams identified a composition of 1% alkyd, 9% Tween 80, and 90% water where spontaneous production of nanoemulsions occurred. The pH, droplet size, and zeta potential of all formulations were in the range of 6.4–6.6, 11–14 nm, and −6 mV to −8 mV, respectively. Rheological studies showed that the nanoemulsions displayed non-Newtonian shear thinning behavior at low shear rates up to 20 s−1 with conversion to Newtonian behavior above this shear rate. All nanoemulsions were found to be stable against phase separation on storage at 4°C and 25°C for three months. Short oil length alkyd nanoemulsions exhibited significantly higher stability compared with medium and long oil length alkyd nanoemulsions, as demonstrated by an absence of phase separation and only minor changes of droplet size on storage at an elevated temperature of 45°C for 3 months. The drug carrying capacity and storage stability of the nanoemulsions were assessed using phenytoin. The entrapment efficiency of alkyd nanoemulsions was in excess of 90% and loss of phenytoin content was restricted to less than 4% during storage of the nanoemulsions for three months at 4°C, 25°C, and 45°C. Taken together, these findings indicate that nanoemulsions prepared from palm kernel oil-based alkyds offer potential as nanocarriers for drug delivery applications.

  20. Gynecomastia and drugs: a critical evaluation of the literature.

    Science.gov (United States)

    Nuttall, Frank Q; Warrier, Rohit S; Gannon, Mary C

    2015-05-01

    A large number of medications have been implicated in the genesis of gynecomastia. However, gynecomastia is common in men, asymptomatic, increases with age, and is considered to be due to an increased estradiol/testosterone ratio. This complicates the interpretation of medication-related gynecomastia. Therefore, we have reviewed the literature in order to assess the data relating gynecomastia onset with utilization of specific medications. The literature was searched in PubMed and the Ovid/Medline databases from the 1946 to January 2015 with the search terminology of "gynecomastia, drugs/medications." A few other articles were found and included. One hundred ten publications were reviewed. Sixty-three were single case reports. There were 24 population-based studies of which 8 were HIV-infected patients treated with antiretroviral agents. Among the case reports, 49 were for individual medications, and 2 were reports of antineoplastic or antiretroviral drug regimens. In the great majority, mastodynia with or without breast enlargement was present and referred to as gynecomastia. Generally, hormonal profiles could not explain the breast enlargement. The pain/tenderness and breast enlargement resolved spontaneously over time. Many different medications have been associated with the presence of "gynecomastia." Generally, it presents as a syndrome characterized by a single painful/tender breast (mastodynia) associated with breast enlargement and is transient. We suggest that these cases be referred to as an acute gynecomastia syndrome. This syndrome also occurs independent of medication use. Thus, in an individual patient, whether it is medication induced often remains uncertain. The pathogenesis remains unknown.

  1. Formulation of Bioadhesive Carbomer Gel Incorporating Drug ...

    African Journals Online (AJOL)

    incorporated into carbomer gel and evaluated for drug release. Results: ... localized delivery system for the treatment inflammation and infection in periodontal pockets. ..... loaded with diclofenac sodium for intra- articular administration. J Drug ...

  2. Patient Awareness of Local Drug Price Variation and the Factors That Influence Pharmacy Choice: A Cross-sectional Survey Study

    Science.gov (United States)

    Brodsky, Spencer D; Awosika, Olabola D; Eleryan, Misty G; Rengifo-Pardo, Monica; Kuang, Xiangyu; Amdur, Richard L; Ehrlich, Alison

    2017-12-01

    BACKGROUND: High out-of-pocket drug expenditures are increasingly common in dermatology. Patients may not be aware that prices vary among pharmacies and consequently may not shop for the lowest cost. OBJECTIVE: To determine what factors influence pharmacy choice and the effect of providing local prescription prices on pharmacy selection. We hypothesized that patients do not "shop around" due to lack of knowledge of price variation and would choose a pharmacy based on costs if educated on price disparity. METHODS: Between July and August 2016, we administered a cross-sectional anonymous survey to adults visiting four outpatient clinics at an academic tertiary care center in Washington, D.C. Participants answered questions before and after viewing a list of prescription drug prices from local pharmacies. RESULTS: 287 surveys were administered to a convenience sample of adults (age ≥ 18 and literate in English). Of the 287 participants, 218 fully completed the survey; 55.1% were women and 40.5% were over age 40. When considering a cost savings of $10-25, 65% would switch pharmacies if the distance were the same, and 21.3% would switch if the distance were 45-minutes further. After price education, fewer participants felt that drug price knowledge would ultimately influence pharmacy choice (P less than 0.0001). However, respondents' intended frequency of researching price online, calling a pharmacy to ask about price, and comparing price between pharmacies before filling a prescription all increased, compared to prior self-reported frequencies (P less than 0.001). Specifically, participants with $75,000-$99,999 income were more likely to compare prices than those with income below $45,000 (odds ratio [OR], 4.62; 95% confidence interval [CI], 1.24-17.28). CONCLUSION: In this study, pharmacy choice was more influenced by convenience than cost prior to drug price education. However, price education ultimately impacted intent to research prescription drug prices before

  3. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    International Nuclear Information System (INIS)

    Li, Xiaoguang; Qian, Hua; Miyamoto, Fusako; Naito, Takeshi; Kawaji, Kumi; Kajiwara, Kazumi; Hattori, Toshio; Matsuoka, Masao; Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka

    2012-01-01

    Highlights: ► We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. ► The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. ► In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, “phenotypic drug evaluation”, may be applicable for the evaluation of various antiviral drugs in vivo.

  4. Operationalising an effective monitoring and evaluation system for local government: Considerations for best practice

    Directory of Open Access Journals (Sweden)

    Paul Kariuki

    2017-11-01

    Conclusion: The article concluded that effective monitoring and evaluation in local government that is responsive to citizens’ needs is a non-negotiable imperative for government. It recommended that municipalities be adequately resourced with competent monitoring and evaluation human personnel. This is important for strengthening their capacity to deliver efficient monitoring and evaluation services.

  5. Simulated Evaluation of Drug-Impaired Psychomotor Performance

    OpenAIRE

    Richmond R

    2014-01-01

    The purpose of this placebo-controlled, randomized-crossover study was to evaluate a computer-based divided-attention task as a method for measure impaired human psychomotor performance. The ability of the divided-attention task to detect and differentiate was evaluated using single oral doses of placebo, caffeine and diphenhydramine. Ten healthy men were the subjects of the study. Subject performance on divided-attention was compared with tests of short-term memory and a set of visual analog...

  6. Development and Optimization of Polymeric Self-Emulsifying Nanocapsules for Localized Drug Delivery: Design of Experiment Approach

    Directory of Open Access Journals (Sweden)

    Jyoti Wadhwa

    2014-01-01

    Full Text Available The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil, X2 (polymeric emulsifier, and X3 (adsorbent, was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1 and encapsulation efficiency (Y2 of the formulation. Polymeric nanocapsules with an average diameter of 100–180 nm and an encapsulation efficiency of 64.85 ± 0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (Cmax 200 ng/mL that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0–2 h in upper GIT; 2–4 h in small intestine; and 4–24 h in the lower intestine. Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 μM in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.

  7. Inhibition of the development of myringosclerosis by local administration of fenspiride, an anti-inflammatory drug.

    Science.gov (United States)

    Mattsson, C; Hellström, S

    1997-01-01

    Earlier studies have revealed a relationship between the development of myringosclerosis and oxygen-derived free radicals. The latter can be blocked by the anti-inflammatory drug fenspiride. The present study was undertaken to test the ability of fenspiride to prevent myringosclerosis from developing during healing of the tympanic membrane. Myringotomized rats were treated with either topical applications or intraperitoneal injections of fenspiride for 12 days, after which the tympanic membranes were examined by otomicroscopy and studied histologically by light microscopy. Topically applied fenspiride was found to inhibit the development of sclerotic lesions, whereas intraperitoneal injections were ineffective.

  8. Tests to evaluate public health disease reporting systems in local public health agencies (electronic resource)

    National Research Council Canada - National Science Library

    Ricci, Karen; Lurie, Nicole; Stoto, Michael A; Wasserman, Jeffrey; Dausey, David J; Meade, Barbara; Diamond, Alexis; Molander, Roger C

    2005-01-01

    ... to evaluate the ability to receive and respond to case reports 24 hours a day, 7 days a week. We refined these tests by beta-testing them at 20 metropolitan area local public health agencies across the country over the course of 10 months. The contents of this manual will be of interest to public health professionals at the state and local l...

  9. Tests to evaluate public health disease reporting systems in local public health agencies

    National Research Council Canada - National Science Library

    Dausey, David J

    2005-01-01

    ... to evaluate the ability to receive and respond to case reports 24 hours a day, 7 days a week. We refined these tests by beta-testing them at 20 metropolitan area local public health agencies across the country over the course of 10 months. The contents of this manual will be of interest to public health professionals at the state and local l...

  10. Prevention of Intraabdominal Adhesions by Local and Systemic Administration of Immunosuppressive Drugs

    Science.gov (United States)

    Peker, Kemal; Inal, Abdullah; Sayar, Ilyas; Sahin, Murat; Gullu, Huriye; Inal, Duriye Gul; Isik, Arda

    2013-01-01

    Background: Intraperitoneal adhesion formation is a serious postsurgical issue. Adhesions develop after damage to the peritoneum by surgery, irradiation, infection or trauma. Objectives: Using a rat model, we compared the effectiveness of systemic and intraperitoneally administered common immunosuppressive drugs for prevention of postoperative intraperitoneal adhesions. Materials and Methods: Peritoneal adhesions were induced in 98 female Wistar-Albino rats by cecal abrasion and peritoneal excision. Rats were randomly separated into seven groups, each containing fourteen rats, and the standard experimental model was applied to all of rats. 14 days later, rats were euthanized, intraperitoneal adhesions were scored and tissues were examined histologically using hematoxylin/eosin and Masson’s trichrome staining. Results: Throughout the investigation, no animal died during or after surgery. In all of experimental groups, decrease in fibrosis was statistically significant. Decrease in fibrosis was most prominently in intraperitoneal tacrolimus group (P = 0.000), and decrease was least in intraperitoneal cyclosporine group (P = 0.022). Vascular proliferation was significantly decreased in all experimental groups (P < 0.05) except for systemic tacrolimus group (P = 0.139). Most prominent reduction in vascular proliferation was in intraperitoneal tacrolimus group (P = 0.000). Conclusions: Administration of immunosuppressive drugs is effective for prevention of intraperitoneal adhesions. PMID:24693396

  11. Tuberculosis therapeutics: Engineering of nanomedicinal systems for local delivery of targeted drug cocktails

    Science.gov (United States)

    D'Addio, Suzanne M.

    In this thesis, a multifunctional nanocarrier drug delivery system was investigated and optimized to improve tuberculosis therapy by promoting the intracellular delivery of high payloads of antibiotics. To meet the needs of a patient population which continues to grow by close to 10 million people a year, innovative therapeutics must be formulated by robust and scalable processes. We use Flash NanoPrecipitation for the continuous precipitation of nanocarriers by block copolymer directed assembly, which enables the development of nanocarriers with tunable properties. Stable nanocarriers of Rifampicin and a hydrophobic Rifampicin prodrug have efficacy against tuberculosis in vitro that is equivalent to the soluble Rifampicin. To overcome poor in vivo efficacy of the recently discovered antitubercular drug SQ641, we co-encapsulate SQ641 and Cyclosporine A in a stable aqueous nanocarrier suspension, which enables drug administration and also enhances intracellular accumulation and antitubercular efficacy relative to SQ641 in solution. Since the mannose receptor is involved in the phagocytosis of tuberculosis bacilli, we modify the surface of nanocarriers with mannoside residues to target specific intracellular accumulation in macrophages. The surface density of mannoside terminated polyethylene glycol chains was controlled between 0 and 75% and in vitro cellular association reveals a 9% surface density is optimal for internalization mediated by the mannose receptor. We explore the preparation of large, porous aerosol carrier particles of with tunable deposition characteristics by spray freeze drying with ultrasonic atomization for direct dosing to the lungs. Nanocarriers are loaded at 3 - 50 wt% in mannitol particles with constant size, limited nanocarrier aggregation, and 63% dose delivered to the lungs, as determined by in vitro cascade impaction. There has been a lag in the development of new technologies to facilitate development and commercialization of

  12. Receptor localization of steroid hormones and drugs: discoveries through the use of thaw-mount and dry-mount autoradiography

    Directory of Open Access Journals (Sweden)

    Stumpf W.E.

    1998-01-01

    Full Text Available The history of receptor autoradiography, its development and applications, testify to the utility of this histochemical technique for localizing radiolabeled hormones and drugs at cellular and subcellular sites of action in intact tissues. Localization of diffusible compounds has been a challenge that was met through the introduction of the "thaw-mount" and "dry-mount" autoradiographic techniques thirty years ago. With this cellular receptor autoradiography, used alone or combined with other histochemical techniques, sites of specific binding and deposition in vivo and in vitro have been characterized. Numerous discoveries, some reviewed in this article, provided information that led to new concepts and opened new areas of research. As an example, in recent years more than fifty target tissues for vitamin D have been specified, challenging the conventional view about the main biological role of vitamin D. The functions of most of these vitamin D target tissues are unrelated to the regulation of systemic calcium homeostasis, but pertain to the (seasonal regulation of endo- and exocrine secretion, cell proliferation, reproduction, neural, immune and cardiovascular responses, and adaptation to stress. Receptor autoradiography with cellular resolution has become an indispensable tool in drug research and development, since information can be obtained that is difficult or impossible to gain otherwise

  13. Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

    Science.gov (United States)

    Krukiewicz, Katarzyna; Zak, Jerzy K

    2016-05-01

    Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Evaluation of a Peer-Led Drug Abuse Risk Reduction Project for Runaway/Homeless Youths.

    Science.gov (United States)

    Fors, Stuart W.; Jarvis, Sara

    1995-01-01

    Evaluates the Drug Prevention in Youth risk reduction program that was implemented in shelters for runaway/homeless youths in the southeastern United States. An evaluation strategy was developed allowing for comparisons between peer-led, adult-led and nonintervention groups. Well-trained and motivated peer/near-peer leaders made particularly…

  15. Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization.

    Science.gov (United States)

    Sawyer, Andrew J; Kyriakides, Themis R

    2016-02-01

    Extracellular matrix is composed of a complex array of molecules that together provide structural and functional support to cells. These properties are mainly mediated by the activity of collagenous and elastic fibers, proteoglycans, and proteins such as fibronectin and laminin. ECM composition is tissue-specific and could include matricellular proteins whose primary role is to modulate cell-matrix interactions. In adults, matricellular proteins are primarily expressed during injury, inflammation and disease. Particularly, they are closely associated with the progression and prognosis of cardiovascular and fibrotic diseases, and cancer. This review aims to provide an overview of the potential use of matricellular proteins in drug delivery including the generation of therapeutic agents based on the properties and structures of these proteins as well as their utility as biomarkers for specific diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Blood pressure reduction, persistence and costs in the evaluation of antihypertensive drug treatment – a review

    Directory of Open Access Journals (Sweden)

    Hasford Joerg

    2009-03-01

    Full Text Available Abstract Background Blood pressure lowering drugs are usually evaluated in short term trials determining the absolute blood pressure reduction during trough and the duration of the antihypertensive effect after single or multiple dosing. A lack of persistence with treatment has however been shown to be linked to a worse cardiovascular prognosis. This review explores the blood pressure reduction and persistence with treatment of antihypertensive drugs and the cost consequences of poor persistence with pharmaceutical interventions in arterial hypertension. Methods We have searched the literature for data on blood pressure lowering effects of different antihypertensive drug classes and agents, on persistence with treatment, and on related costs. Persistence was measured as patients' medication possession rate. Results are presented in the form of a systematic review. Results Angiotensin II receptor blocker (ARBs have a competitive blood pressure lowering efficacy compared with ACE-inhibitors (ACEi and calcium channel blockers (CCBs, beta-blockers (BBs and diuretics. 8 studies describing the persistence with treatment were identified. Patients were more persistent on ARBs than on ACEi and CCBs, BBs and diuretics. Thus the product of blood pressure lowering and persistence was higher on ARBs than on any other drug class. Although the price per tablet of more recently developed drugs (ACEi, ARBs is higher than that of older ones (diuretics and BBs, the newer drugs result in a more favourable cost to effect ratio when direct drug costs and indirect costs are also considered. Conclusion To evaluate drugs for the treatment of hypertension several key variables including the blood pressure lowering effect, side effects, compliance/persistence with treatment, as well as drug costs and direct and indirect costs of medical care have to be considered. ARBs, while nominally more expensive when drug costs are considered only, provide substantial cost savings

  17. In Vivo Optical Imaging for Targeted Drug Kinetics and Localization for Oral Surgery and Super-Resolution, Facilitated by Printed Phantoms

    Science.gov (United States)

    Bentz, Brian Z.

    Many human cancer cell types over-express folate receptors, and this provides an opportunity to develop targeted anti-cancer drugs. For these drugs to be effective, their kinetics must be well understood in vivo and in deep tissue where tumors occur. We demonstrate a method for imaging these parameters by incorporating a kinetic compartment model and fluorescence into optical diffusion tomography (ODT). The kinetics were imaged in a live mouse, and found to be in agreement with previous in vitro studies, demonstrating the validity of the method and its feasibility as an effective tool in preclinical drug development studies. Progress in developing optical imaging for biomedical applications requires customizable and often complex objects known as "phantoms" for testing and evaluation. We present new optical phantoms fabricated using inexpensive 3D printing methods with multiple materials, allowing for the placement of complex inhomogeneities in heterogeneous or anatomically realistic geometries, as opposed to previous phantoms which were limited to simple shapes formed by molds or machining. Furthermore, we show that Mie theory can be used to design the optical properties to match a target tissue. The phantom fabrication methods are versatile, can be applied to optical imaging methods besides diffusive imaging, and can be used in the calibration of live animal imaging data. Applications of diffuse optical imaging in the operating theater have been limited in part due to computational burden. We present an approach for the fast localization of arteries in the roof of the mouth that has the potential to reduce complications. Furthermore, we use the extracted position information to fabricate a custom surgical guide using 3D printing that could protect the arteries during surgery. The resolution of ODT is severely limited by the attenuation of high spatial frequencies. We present a super-resolution method achieved through the point localization of fluorescent

  18. Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting.

    Science.gov (United States)

    Pan, Lucy Yan; Salas-Solano, Oscar; Valliere-Douglass, John F

    Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains. Our results for two case studies are shown here. The first study was aimed at defining the conformational changes of mAbs induced by deglycosylation. We found that two residues in C H 2 domain (D268 and E297) show significantly enhanced side chain accessibility upon deglycosylation. This site-specific result highlighted the advantage of monitoring the labeling kinetics at the amino acid level as opposed to the peptide level, which would result in averaging out of highly localized conformational differences. The second study was designed to assess conformational effects brought on by conjugation of mAbs with drug-linkers. All 59 monitored carboxyl residues displayed similar solvent-accessibility between the ADC and mAb under native conditions, which suggests the ADC and mAb share similar side chain conformation. The findings are well correlated and complementary with results from other assays. This work illustrated that site-specific CGF is capable of pinpointing local conformational changes in mAbs or ADCs that might arise during development and manufacturing. The methodology can be readily implemented within the industry to provide comprehensive conformational assessment of these molecules.

  19. Evaluation of the microscopic observational drug susceptibility assay for rapid and efficient diagnosis of multi-drug resistant tuberculosis

    Directory of Open Access Journals (Sweden)

    R P Lazarus

    2012-01-01

    Full Text Available Purpose: Tuberculosis (TB is endemic in India and the burden of multi-drug-resistant tuberculosis (MDR-TB is high. Early detection of MDR-TB is of primary importance in controlling the spread of TB. The microscopic observational drug susceptibility (MODS assay has been described as a cost-effective and rapid method by which mycobacterial culture and the drug susceptibility test (DST can be done at the same time. Materials and Methods: A total of 302 consecutive sputum samples that were received in an accredited mycobacteriology laboratory for conventional culture and DST were evaluated by the MODS assay. Results: In comparison with conventional culture on Lowenstein Jensen (LJ media, the MODS assay showed a sensitivity of 94.12% and a specificity of 89.39% and its concordance with the DST by the proportion method on LJ media to isoniazid and rifampicin was 90.8% and 91.5%, respectively. The turnaround time for results by MODS was 9 days compared to 21 days by culture on LJ media and an additional 42 days for DST by the 1% proportion method. The cost of performing a single MODS assay was Rs. 250/-, compared to Rs. 950/- for culture and 1st line DST on LJ. Conclusion: MODS was found to be a sensitive and rapid alternative method for performing culture and DST to identify MDR-TB in resource poor settings.

  20. Evaluation and modeling of the eutectic composition of various drug-polyethylene glycol solid dispersions.

    Science.gov (United States)

    Baird, Jared A; Taylor, Lynne S

    2011-06-01

    The purpose of this study was to gain a better understanding of which factors contribute to the eutectic composition of drug-polyethylene glycol (PEG) blends and to compare experimental values with predictions from the semi-empirical model developed by Lacoulonche et al. Eutectic compositions of various drug-PEG 3350 solid dispersions were predicted, assuming athermal mixing, and compared to experimentally determined eutectic points. The presence or absence of specific interactions between the drug and PEG 3350 were investigated using Fourier transform infrared (FT-IR) spectroscopy. The eutectic composition for haloperidol-PEG and loratadine-PEG solid dispersions was accurately predicted using the model, while predictions for aceclofenac-PEG and chlorpropamide-PEG were very different from those experimentally observed. Deviations in the model prediction from ideal behavior for the systems evaluated were confirmed to be due to the presence of specific interactions between the drug and polymer, as demonstrated by IR spectroscopy. Detailed analysis showed that the eutectic composition prediction from the model is interdependent on the crystal lattice energy of the drug compound (evaluated from the melting temperature and the heat of fusion) as well as the nature of the drug-polymer interactions. In conclusion, for compounds with melting points less than 200°C, the model is ideally suited for predicting the eutectic composition of systems where there is an absence of drug-polymer interactions.

  1. FORMULATION AND EVALUATION OF FLOATING DRUG DELIVERY SYSTEM OF AMOXYCILLIN TRIHYDRATE

    OpenAIRE

    Marella Radhakrishna; K.G.Parthiban; Nelluri Ramarao; Nagapuri Santhoshi Deepika; Perumulla Abhishek

    2012-01-01

    The present study was designed to formulate and evaluate balanced Floating Drug Delivery Systems as controlled release modules, which prolongs the release rate of the drugs. Amoxycillin is an anti- bacterial acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell walls of both Gram-positive and Gram-negative bacteria. Helicobacter pylori exists in the gastric mucous layer or ...

  2. Evaluating Small Sphere Limit of the Wang-Yau Quasi-Local Energy

    Science.gov (United States)

    Chen, Po-Ning; Wang, Mu-Tao; Yau, Shing-Tung

    2018-01-01

    In this article, we study the small sphere limit of the Wang-Yau quasi-local energy defined in Wang and Yau (Phys Rev Lett 102(2):021101, 2009, Commun Math Phys 288(3):919-942, 2009). Given a point p in a spacetime N, we consider a canonical family of surfaces approaching p along its future null cone and evaluate the limit of the Wang-Yau quasi-local energy. The evaluation relies on solving an "optimal embedding equation" whose solutions represent critical points of the quasi-local energy. For a spacetime with matter fields, the scenario is similar to that of the large sphere limit found in Chen et al. (Commun Math Phys 308(3):845-863, 2011). Namely, there is a natural solution which is a local minimum, and the limit of its quasi-local energy recovers the stress-energy tensor at p. For a vacuum spacetime, the quasi-local energy vanishes to higher order and the solution of the optimal embedding equation is more complicated. Nevertheless, we are able to show that there exists a solution that is a local minimum and that the limit of its quasi-local energy is related to the Bel-Robinson tensor. Together with earlier work (Chen et al. 2011), this completes the consistency verification of the Wang-Yau quasi-local energy with all classical limits.

  3. Development and Evaluation of Cefadroxil Drug Loaded Biopolymeric Films Based on Chitosan-Furfural Schiff Base

    Science.gov (United States)

    Dixit, Ritu B.; Uplana, Rahul A.; Patel, Vishnu A.; Dixit, Bharat C.; Patel, Tarosh S.

    2010-01-01

    Cefadroxil drug loaded biopolymeric films of chitosan-furfural schiff base were prepared by reacting chitosan with furfural in presence of acetic acid and perchloric acid respectively for the external use. Prepared films were evaluated for their strength, swelling index, thickness, drug content, uniformity, tensile strength, percent elongation, FTIR spectral analysis and SEM. The results of in vitro diffusion studies revealed that the films exhibited enhanced drug diffusion as compared to the films prepared using untreated chitosan. The films also demonstrated good to moderate antibacterial activities against selective gram positive and gram negative bacteria. PMID:21179325

  4. Sustained Release and Cytotoxicity Evaluation of Carbon Nanotube-Mediated Drug Delivery System for Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

    Full Text Available Carbon nanotubes (CNTs have been widely utilized as a novel drug carrier with promising future applications in biomedical therapies due to their distinct characteristics. In the present work, carboxylic acid-functionalized single-walled carbon nanotubes (f-SWCNTs were used as the starting material to react with anticancer drug, BA to produce f-SWCNTs-BA conjugate via π-π stacking interaction. The conjugate was extensively characterized for drug loading capacity, physicochemical properties, surface morphology, drug releasing characteristics, and cytotoxicity evaluation. The results indicated that the drug loading capacity was determined to be around 20 wt% and this value has been verified by thermogravimetric analysis. The binding of BA onto the surface of f-SWCNTs was confirmed by FTIR and Raman spectroscopies. Powder XRD analysis showed that the structure of the conjugate was unaffected by the loading of BA. The developed conjugate was found to release the drug in a controlled manner with a prolonged release property. According to the preliminary in vitro cytotoxicity studies, the conjugate was not toxic in a standard fibroblast cell line, and anticancer activity was significantly higher in A549 than HepG2 cell line. This study suggests that f-SWCNTs could be developed as an efficient drug carrier to conjugate drugs for pharmaceutical applications in cancer chemotherapies.

  5. 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 ...

  6. Development and evaluation of diclofenac sodium thermorevesible subcutaneous drug delivery system.

    Science.gov (United States)

    Nasir, Fazli; Iqbal, Zafar; Khan, Jamshaid A; Khan, Abad; Khuda, Fazli; Ahmad, Lateef; Khan, Amirzada; Khan, Abbas; Dayoo, Abdullah; Roohullah

    2012-12-15

    The objective of current work was to develop and evaluate thermoreversible subcutaneous drug delivery system for diclofenac sodium. The poloxamer 407, methyl cellulose, hydroxypropyl methyl cellulose and polyethylene glycol were used alone and in combination in different ratios to design the delivery system. The physical properties like Tsol-gel, viscosity, clarity of solution and gel were evaluated. The in vitro release of the drug delivery system was evaluated using membrane less method and the drug release kinetics and mechanism was predicted by applying various mathematical models to the in vitro dissolution data. Rabbits were used as in vivo model following subcutaneous injection to predict various pharmacokinetics parameters by applying Pk-Summit software. The in vitro and in vivo data revealed that the system consisting of the poloxamer 407 in concentration of 20% (DP20) was the most capable formulation for extending the drug release and maintaining therapeutic blood level of DS for longer duration (144 h). The data obtained for drug content after autoclaving the solutions indicate that autoclaving results in 6% degradation of DS. The data also suggested that the studied polymers poloxamer, MC and PG are good candidate to extend the drug release possessing a unique thermoreversible property. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Evaluation of contact sensitivity to topical drugs in patients with contact dermatitis

    Directory of Open Access Journals (Sweden)

    Bilge Bülbül Şen

    2013-03-01

    Full Text Available Background and Design: Topical drugs are an important group of contact allergens. The present study aimed to evaluate contact sensitivity to topical drugs in patients with contact dermatitis. Materials and Methods: Between 2003 and 2008, 129 patients were followed up at the Department of Dermatology at Ankara University School of Medicine with clinically suspected contact sensitivity to topical drugs. In this study, the patch test reactions to the European Standard Battery and topical drugs used by the patients and medicament patch test results were evaluated. Results: Positive patch test reaction to one or more allergens was found in 80 (62.0% of 129 patients included in the study. Sixty-one of the 80 patients (61/129, 47.3% had positive patch test reaction to medicaments. Medicament sensitivity was detected in 37.9% (49/129 of subjects. Nitrofurazone was found to be the most common allergen (18.6%. Discussion: The present study showed that topical drugs are a frequent cause of allergic contact dermatitis. Therefore, the probability of contact sensitivity to topical drugs should also be considered in patients with the clinical diagnosis of allergic contact dermatitis and, suspected cases should be evaluated further with patch testing in order to find the responsible allergens.

  8. Localized increase of tissue oxygen tension by magnetic targeted drug delivery

    Science.gov (United States)

    Liong, Celine; Ortiz, Daniel; Ao-ieong, Eilleen; Navati, Mahantesh S.; Friedman, Joel M.; Cabrales, Pedro

    2014-07-01

    Hypoxia is the major hindrance to successful radiation therapy of tumors. Attempts to increase the oxygen (O2) tension (PO2) of tissue by delivering more O2 have been clinically disappointing, largely due to the way O2 is transported and released by the hemoglobin (Hb) within the red blood cells (RBCs). Systemic manipulation of O2 transport increases vascular resistance due to metabolic autoregulation of blood flow to prevent over oxygenation. This study investigates a new technology to increase O2 delivery to a target tissue by decreasing the Hb-O2 affinity of the blood circulating within the targeted tissue. As the Hb-O2 affinity decreases, the tissue PO2 to satisfy tissue O2 metabolic needs increases without increasing O2 delivery or extraction. Paramagnetic nanoparticles (PMNPs), synthetized using gadolinium oxide, were coated with the cell permeable Hb allosteric effector L35 (3,5-trichlorophenylureido-phenoxy-methylpropionic acid). L35 decreases Hb affinity for O2 and favors the release of O2. The L35-coated PMNPs (L35-PMNPs) were intravenously infused (10 mg kg-1) to hamsters instrumented with the dorsal window chamber model. A magnetic field of 3 mT was applied to localize the effects of the L35-PMNPs to the window chamber. Systemic O2 transport characteristics and microvascular tissue oxygenation were measured after administration of L35-PMNPs with and without magnetic field. The tissue PO2 in untreated control animals was 25.2 mmHg. L35-PMNPs without magnetic field decreased tissue PO2 to 23.4 mmHg, increased blood pressure, and reduced blood flow, largely due to systemic modification of Hb-O2 affinity. L35-PMNPs with magnetic field increased tissue PO2 to 27.9 mmHg, without systemic or microhemodynamic changes. These results indicate that localized modification of Hb-O2 affinity can increase PO2 of target tissue without affecting systemic O2 delivery or triggering O2 autoregulation mechanisms. This technology can be used to treat local hypoxia and to

  9. Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin.

    Science.gov (United States)

    Brown, M B; Jones, S A

    2005-05-01

    Hyaluronic acid (HA) is a naturally occurring polyanionic, polysaccharide that consists of N-acetyl-D-glucosamine and beta-glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock-absorbing role. The unique viscoelastic nature of HA along with its biocompatibility and non-immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, HA has been investigated as a drug delivery agent for various routes of administration, including ophthalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% HA gel, Solaraze, for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost-effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5-fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of HA together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.

  10. Evaluation of Egg Quality Traits of Local Chickens in the Humid ...

    African Journals Online (AJOL)

    Four hundred and thirty six (436) eggs laid by seven genotypes of local chickens within 56 days were used to evaluate egg quality traits. The genotypes evaluated were the homozygous naked neck (Na/Na) and frizzle (F/F), heterozygous naked neck (Na/na) and frizzle (F/na), reciprocal crosses between naked neck and ...

  11. Evaluation of new injection and cavity preparation model in local anesthesia teaching

    NARCIS (Netherlands)

    Yekta, S.S.; Lampert, F.; Kazemi, S.; Kazemi, R.; Brand, H.S.; Baart, J.A.; Mazandarani, M.

    2013-01-01

    The aim of this study was to evaluate a recently developed preclinical injection and cavity preparation model in local anesthesia. Thirty-three dental students administered an inferior alveolar nerve block injection in the model, followed by preparation on a tooth. The injection was evaluated by

  12. Assessment of a Pharmaceutical Advertisement Analysis Module in a Drug Literature Evaluation Course.

    Science.gov (United States)

    Amin, Mohamed Ezzat Khamis; Fattouh, Youssef

    2017-08-01

    Objective. To evaluate the impact of an educational module on students' self-efficacy when analyzing the content of promotional drug brochures (PDBs) and to assess the students' value of PDBs' as an educational tool. Methods. Third-year bachelor of pharmacy students participated in a one-hour lecture and a two-hour laboratory. Students completed a survey before and after participating in the module. Results. The module elicited a statistically significant change in students' self-efficacy beliefs regarding evaluating promotional drug brochures, while the average perceived value of promotional drug brochures did not change significantly after the module. Conclusion. A brief educational module can increase students' self-efficacy in evaluating the content of PDBs.

  13. Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

    Science.gov (United States)

    Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

    2017-01-01

    Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation.

    Science.gov (United States)

    Ha, Michael A; Sieg, Adam C

    2017-02-01

    Extracorporeal membrane oxygenation (ECMO) is a life-support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965-July 2016), EMBASE (1965-July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward. © 2016 Pharmacotherapy Publications, Inc.

  15. A replication and methodological critique of the study "Evaluating drug trafficking on the Tor Network"

    DEFF Research Database (Denmark)

    Munksgaard, Rasmus; Demant, Jakob Johan; Branwen, Gwern

    2016-01-01

    The development of cryptomarkets has gained increasing attention from academics, including growing scientific literature on the distribution of illegal goods using cryptomarkets. Dolliver's 2015 article “Evaluating drug trafficking on the Tor Network: Silk Road 2, the Sequel” addresses this theme...... by evaluating drug trafficking on one of the most well-known cryptomarkets, Silk Road 2.0. The research on cryptomarkets in general—particularly in Dolliver's article—poses a number of new questions for methodologies. This commentary is structured around a replication of Dolliver's original study...

  16. Evaluation of skin absorption of drugs from topical and transdermal formulations

    Directory of Open Access Journals (Sweden)

    André Luís Morais Ruela

    Full Text Available ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

  17. Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Hyejin Kim

    2013-01-01

    Full Text Available Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μg/mL of moxifloxacin; 93.6%, 1.0 μg/mL of levofloxacin; 97.5%, 2.5 μg/mL of kanamycin; 90.6%, 2.5 μg/mL of capreomycin; 86.2%, 5.0 μg/mL of ethionamide; and 90.8%, 2.0 μg/mL of ρ-aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ-aminosalicylic acid is required.

  18. Development and effect of different bioactive silicate glass scaffolds: in vitro evaluation for use as a bone drug delivery system.

    Science.gov (United States)

    Soundrapandian, Chidambaram; Mahato, Arnab; Kundu, Biswanath; Datta, Someswar; Sa, Biswanath; Basu, Debebrata

    2014-12-01

    Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO2-Na2O-ZnO-CaO-MgO-P2O5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63-66% porous and 5-50μm almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas-Korsmeyer release pattern based on Fickian diffusion, while 0.5-1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain

  19. Building a structured monitoring and evaluating system of postmarketing drug use in Shanghai.

    Science.gov (United States)

    Du, Wenmin; Levine, Mitchell; Wang, Longxing; Zhang, Yaohua; Yi, Chengdong; Wang, Hongmin; Wang, Xiaoyu; Xie, Hongjuan; Xu, Jianglong; Jin, Huilin; Wang, Tongchun; Huang, Gan; Wu, Ye

    2007-01-01

    In order to understand a drug's full profile in the post-marketing environment, information is needed regarding utilization patterns, beneficial effects, ADRs and economic value. China, the most populated country in the world, has the largest number of people who are taking medications. To begin to appreciate the impact of these medications, a multifunctional evaluation and surveillance system was developed, the Shanghai Drug Monitoring and Evaluative System (SDMES). Set up by the Shanghai Center for Adverse Drug Reaction Monitoring in 2001, the SDMES contains three databases: a population health data base of middle aged and elderly persons; hospital patient medical records; and a spontaneous ADR reporting database. Each person has a unique identification and Medicare number, which permits record-linkage within and between these three databases. After more than three years in development, the population health database has comprehensive data for more than 320,000 residents. The hospital database has two years of inpatient medical records from five major hospitals, and will be increasing to 10 hospitals in 2007. The spontaneous reporting ADR database has collected 20,205 cases since 2001 from approximately 295 sources, including hospitals, pharmaceutical companies, drug wholesalers and pharmacies. The SDMES has the potential to become an important national and international pharmacoepidemiology resource for drug evaluation.

  20. San Jose, California: Evaluating Local Solar Energy Generation Potential (City Energy: From Data to Decisions)

    Energy Technology Data Exchange (ETDEWEB)

    Office of Strategic Programs, Strategic Priorities and Impact Analysis Team

    2017-09-29

    This fact sheet "San Jose, California: Evaluating Local Solar Energy Generation Potential" explains how the City of San Jose used data from the U.S. Department of Energy's Cities Leading through Energy Analysis and Planning (Cities-LEAP) and the State and Local Energy Data (SLED) programs to inform its city energy planning. It is one of ten fact sheets in the "City Energy: From Data to Decisions" series.

  1. Curriculum and instructional methods for drug information, literature evaluation, and biostatistics: survey of US pharmacy schools.

    Science.gov (United States)

    Phillips, Jennifer A; Gabay, Michael P; Ficzere, Cathy; Ward, Kristina E

    2012-06-01

    The drug information curriculum in US colleges of pharmacy continues to evolve. The American College of Clinical Pharmacy (ACCP) Drug Information Practice and Research Network (DI PRN) published an opinion paper with specific recommendations regarding drug information education in 2009. Adoption of these recommendations has not been evaluated. To assess which recommendations made in the ACCP DI PRN opinion paper are included in US pharmacy school curricula and characterize faculty qualifications, educational methods, and recent changes in drug information education. An electronic survey was designed using the ACCP DI PRN opinion paper and the Accreditation Council for Pharmacy Education standards and guidelines for accreditation of PharmD programs in the US. Survey questions addressed curricular content within the following categories: drug information, literature evaluation, and biostatistics. A letter including the online survey link was sent via email to the dean of each US college/school of pharmacy (N = 128). Recipients were instructed to forward the email to the individual at their institution who was the most knowledgeable about the content and methodology used for didactic drug information education. Sixty-four responses were included in the final analysis. Of the 19 ACCP DI PRN minimum core concepts, 9 (47%) were included in curricula of all responding institutions; 14 of 19 (74%) were included in curricula for all but 1 institution. In contrast, 5 of 16 concepts (31%) were not formally taught by a number of institutions. Many respondents noted an increased focus on evidence-based medicine, medication safety, and informatics. Although a survey of drug information curricula documented substantial inclusion of the essential concepts presented in the ACCP DI PRN opinion paper, room for improvement remains in drug information curricula in US colleges of pharmacy.

  2. Multicenter evaluation of a new closed system drug-transfer device in reducing surface contamination by antineoplastic hazardous drugs.

    Science.gov (United States)

    Bartel, Sylvia B; Tyler, Timothy G; Power, Luci A

    2018-02-15

    Results of a study to evaluate the effectiveness of a recently introduced closed system drug-transfer device (CSTD) in reducing surface contamination during compounding and simulated administration of antineoplastic hazardous drugs (AHDs) are reported. Wipe samples were collected from 6 predetermined surfaces in compounding and infusion areas of 13 U.S. cancer centers to establish preexisting levels of surface contamination by 2 marker AHDs (cyclophosphamide and fluorouracil). Stainless steel templates were placed over the 6 previously sampled surfaces, and the marker drugs were compounded and infused per a specific protocol using all components of the CSTD. Wipe samples were collected from the templates after completion of tasks and analyzed for both marker AHDs. Aggregated results of wipe sampling to detect preexisting contamination at the 13 study sites showed that overall, 66.7% of samples (104 of 156) had detectable levels of at least 1 marker AHD; subsequent testing after CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156 samples). In the administration areas alone, the rate of preexisting contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the contamination rate was 2.6%. Twenty-six participants rated the CSTD for ease of use, with 100% indicating that they were satisfied or extremely satisfied. A study involving a rigorous protocol and 13 cancer centers across the United States demonstrated that the CSTD reduced surface contamination by cyclophosphamide and fluorouracil during compounding and simulated administration. Participants reported that the CSTD was easy to use. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  3. Using Elite Athletes to Promote Drug Abstinence: Evaluation of a Single-Session School-Based Drug Use Prevention Program Delivered by Junior Hockey Players

    Science.gov (United States)

    Wong, Jennifer

    2016-01-01

    School-based substance use prevention programs are a common method to approaching drug use in youths. Project SOS is a single-session drug prevention program developed by police officers and delivered by elite junior hockey players to students in grades 6 and 7. The current study evaluates the effects of Project SOS at achieving its objectives of…

  4. Evaluating Drug Cost per Response with SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Lopez, Janice M S; Macomson, Brian; Ektare, Varun; Patel, Dipen; Botteman, Marc

    2015-09-01

    The sodium-glucose cotransporter 2 (SGLT2) inhibitors, which include canagliflozin, dapagliflozin, and empagliflozin, represent a new class of antihyperglycemic agents. Few studies have assessed their cost per response, with "cost per response" being the total cost of a select drug, divided by the resulting change in glycated hemoglobin (HbA1c) levels. To examine the drug cost of SGLT2 inhibitors per a reduction in placebo-adjusted 1% HbA1c in patients with type 2 diabetes mellitus who received treatment during 26 weeks with canagliflozin, dapagliflozin, or empagliflozin. The drug cost per response for each of the 3 agents individually was assessed based on data from a subset of clinical trials discussed in the prescribing information for each drug that were all placebo-controlled studies evaluating each drug as monotherapy, dual therapy (combined with metformin), and triple therapy (combined with metformin and a sulfonylurea) in patients with uncontrolled, type 2 diabetes mellitus. The US 2015 wholesale acquisition cost for each drug was used to calculate each drug's treatment costs over 26 weeks. The average cost per response for each drug was defined as the prescription drug cost of each SGLT2 inhibitor, divided by the average, placebo-adjusted HbA1c reduction at 26 weeks. The drug cost per unit dose was the same for canagliflozin (100 mg or 300 mg), dapagliflozin (5 mg or 10 mg), and empagliflozin (10 mg or 25 mg), at $11.43. The drug cost per placebo-adjusted 1% HbA1c reduction varied by agent and by dose, as a result of the differences in the treatment responses for each of the 3 drugs. The costs per response for canagliflozin 100 mg as monotherapy, dual therapy, and triple therapy regimens ranged from $2286 to $3355, and for canagliflozin 300 mg, from $1793 to $2702. The costs per response for dapagliflozin 5 mg as monotherapy and dual therapy (triple therapy was not available at the time of the study) ranged from $4161 to $5201; the cost for dapagliflozin

  5. Optical microscopy of targeted drug delivery and local distribution in skin of a topical minocycline: implications in translational research and guidance for therapeutic dose selection (Conference Presentation)

    Science.gov (United States)

    Hermsmeier, Maiko; Sawant, Tanvee; Lac, Diana; Yamamoto, Akira; Chen, Xin; Huang, Susan Y.; Nagavarapu, Usha; Evans, Conor L.; Chan, Kin Foong; Daniels, AnnaMarie

    2017-02-01

    Acne vulgaris is a chronic inflammatory skin condition commonly resulting in negative aesthetic and social impacts on those affected. Minocycline, currently available as an oral antibiotic for moderate to severe acne, has a known minimum inhibitory concentration (MIC) for the acne-causing bacterium Propionibacterium acnes (P. acnes) in vitro, with its anti-inflammatory properties also eliciting inhibitory effects on pro-inflammatory molecules. A novel topical gel composition containing solubilized minocycline (BPX-01) has been developed to directly deliver the drug to the skin. Because minocycline is a known fluorophore, fluorescence microscopy and concurrent quantitative measurements were performed on excised human facial skin dosed with different concentrations, in order to determine the spatial distribution of the drug and quantification of its local concentration in the epidermis and the pilosebaceous unit where P. acnes generally reside. Local minocycline delivery confirmed achievement of an adequate therapeutic dose to support clinical studies. Subsequently, a 4-week double-blind, randomized, vehicle controlled clinical study was performed to assess the safety and efficacy of 1% minocycline BPX-01 applied daily. No instances of cutaneous toxicity were reported, and a greater than 1 log reduction of P. acnes count was observed at week 4 with statistical significance from baseline and vehicle control. In addition, no detectable amounts of minocycline in the plasma were reported, suggesting the potential of this new formulation to diminish the known systemic adverse effects associated with oral minocycline. Follow-on clinical plans are underway to further establish the safety of BPX-01 and to evaluate its efficacy against inflammatory acne lesions in a 225 patient multi-center dose-finding study.

  6. Where Local and National Evaluators Meet: Unintended Threats to Ethical Evaluation Practice

    Science.gov (United States)

    Rodi, Michael S.; Paget, Kathleen D.

    2007-01-01

    The ethical work of program evaluators is based on a covenant of honesty and transparency among stakeholders. Yet even under the most favorable evaluation conditions, threats to ethical standards exist and muddle that covenant. Unfortunately, ethical issues associated with different evaluation structures and contracting arrangements have received…

  7. A critical friend: monitoring and evaluation systems, development cooperation and local government. The case of Tuscany.

    Science.gov (United States)

    Rossignoli, Serena; Coticchia, Fabrizio; Mezzasalma, Annarosa

    2015-06-01

    The role of monitoring and evaluation (M&E) systems in the field of development cooperation has globally increased in last decades. International and regional organizations, as well as states, local governments and NGOs have largely adopted the tools provided by M&E in order to enhance transparency, effectiveness and efficiency. The paper aims at verifying how and to what extent the implementation of M&E systems has affected the overall quality of international cooperation projects financed by a local government. After a literature review on M&E in development cooperation, the research analyzes the wide range of activities (evaluation ex-ante, mid-term, final, monitoring, consultancy) carried out by the Evaluation Team of the XY in the last eight years in behalf of an Italian local government: the Region of Tuscany. The paper reveals the strategic significance of adopting M&E systems in the medium-long term. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas.

    Science.gov (United States)

    Grover, Amelia C; Skarulis, Monica; Alexander, H Richard; Pingpank, James F; Javor, Edward D; Chang, Richard; Shawker, Thomas; Gorden, Phil; Cochran, Craig; Libutti, Steven K

    2005-12-01

    Preoperative imaging studies localize insulinomas in less than 50% of patients. Arteriography with calcium stimulation and venous sampling (ASVS) regionalizes greater than 90% of insulinomas but requires specialized expertise and an invasive procedure. This prospective study evaluated laparoscopic exploration with IOUS compared with the other localization procedures in patients with a sporadic insulinoma. Between March 2001 and October 2004, 14 patients (7 women and 7 men; mean age, 53) with an insulinoma were enrolled in an IRB-approved protocol. Computed tomography, magnetic resonance imaging, ultrasound scan, and arteriography with calcium stimulation and venous sampling were performed preoperatively. A surgeon, blinded to the results of the localizing studies, performed a laparoscopic exploration with intraoperative ultrasound (IOUS). At the completion of the exploration, the success of laparoscopy for localization was scored, and the tumor was resected. Twelve of 14 tumors were localized successfully before laparoscopy (noninvasive, 7 of 14; invasive, 11 of 14). Laparoscopic IOUS localized successfully 12 of 14 tumors. All lesions were resected, and all patients were cured (median follow-up, 36 months). Laparoscopic IOUS identified 86% of tumors. The authors consider laparoscopic IOUS to be equivalent to ASVS in localizing insulinomas. Further study is therefore warranted to determine the role of laparoscopy with IOUS in the localization and treatment algorithm for patients with sporadic insulinoma.

  9. A Census of Prison-Based Drug Treatment Programs: Implications for Programming, Policy, and Evaluation

    Science.gov (United States)

    Welsh, Wayne N.; Zajac, Gary

    2004-01-01

    Despite a growing realization that unmeasured programmatic differences influence prison-based drug treatment effectiveness, few attempts to systematically measure such differences have been made. To improve program planning and evaluation in this area, we developed a census instrument to collect descriptive information about 118 prison-based drug…

  10. Therapeutic drug monitoring of infliximab : performance evaluation of three commercial ELISA kits

    NARCIS (Netherlands)

    Schmitz, E.M.H.; van de Kerkhof, D.; Hamann, D.; van Dongen, J.L.J.; Kuijper, P.H.M.; Brunsveld, L.; Scharnhorst, V.; Broeren, M.A.C.

    2016-01-01

    BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX, Remicade®) can aid to optimize therapy efficacy. Many assays are available for this purpose. However, a reference standard is lacking. Therefore, we evaluated the analytical performance, agreement and clinically relevant differences

  11. Evaluation of new drugs in daily clinical practice: anti-TNF alpha in rheumatoid arthritis patients.

    NARCIS (Netherlands)

    Kievit, W.

    2008-01-01

    The objective of this thesis was to explore the value and the validity of data collected in daily clinical practice for drug evaluation and cost-effectiveness studies, using data collected on TNFa blocking agents in rheumatoid arthritis. First, the need for and value of information from daily

  12. [Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

    Science.gov (United States)

    Li, Yuanyuan; Xie, Yanming

    2011-10-01

    The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

  13. 77 FR 69634 - Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing...

    Science.gov (United States)

    2012-11-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0784] Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals... Effectiveness of Anticoccidial Drugs in Food-Producing Animals.'' The guidance provides guidance to industry for...

  14. A rapid in vitro screening system for the identification and evaluation of anticancer drugs

    International Nuclear Information System (INIS)

    Kao, J.W.; Collins, J.L.

    1989-01-01

    We report the development of an in vitro screening system that can be used to identify new anticancer drugs that are specifically cytotoxic for dividing cells. The screening system takes advantage of the potential of many cell lines, including tumor cells, to stop dividing when they are plated at high cell density. The cytotoxic effects of anticancer drugs on dividing (i.e., cells plated at low cell density) and nondividing cells (i.e., cells plated at high cell density) is measured by the incorporation of 51Cr. This in vitro system was evaluated by measuring the cytotoxic effects of the anticancer drugs cisplatin, thiotepa, doxorubicin, methotrexate, and vinblastine on the cell lines B/C-N, ME-180, and MCF-7. In this in vitro system the concentrations of the anticancer drugs that produced significant cytotoxicity on only dividing cells are similar to the concentrations that are used clinically. The fact that this in vitro system is rapid, simple, applicable to many cell types, and able to predict effective concentrations of anticancer drugs should make it useful for the screening of new anticancer drugs and for the design of preclinical studies

  15. Development and evaluation of gastroretentive floating tablets of an antidepressant drug by thermoplastic granulation technique

    Directory of Open Access Journals (Sweden)

    Harshal Ashok Pawar

    2014-06-01

    Full Text Available The present study was undertaken with an aim to formulate, develop and evaluate gastroretentive floating tablets of an antidepressant drug, Venlafaxine HCl (hydrochloride, which release the drug in a sustained manner over a period of 24 h. Three different hydrophobic retardants namely hydrogenated cottonseed oil, carnauba wax, cetyl alcohol and a hydrophilic polymer Methocel® (hydroxy propyl methyl cellulose (HPMC K15M were used in different combinations at different ratios for the preparation of tablets. The tablets were prepared by Hot Melt or Thermoplastic granulation method and evaluated for tablet thickness, hardness, weight variation, friability, floating lag time and in vitro drug release. Formulation F8 with hydrophilic polymer (Methocel® K15M and hydrophobic retardant (carnauba wax in the ratio 1:2.6 (approx. was considered as an optimized formulation. The optimized formulation showed satisfactory sustained drug release and remained buoyant on the surface of the medium for more than 24 h and its release profile was comparable with the marketed formulation (VENTAB-XL 37.5. It can also be concluded that floating drug delivery system of Venlafaxine HCl can be successfully formulated as an approach to increase gastric residence time and thereby improving its bioavailability.

  16. Evaluation of In-Use Stability of Anticoagulant Drug Products: Warfarin Sodium.

    Science.gov (United States)

    Nguyenpho, Agnes; Ciavarella, Anthony B; Siddiqui, Akhtar; Rahman, Ziyaur; Akhtar, Sohail; Hunt, Robert; Korang-Yeboah, Maxwell; Khan, Mansoor A

    2015-12-01

    The objective of the study was to evaluate the stability of warfarin products during use by patients or caregivers. For evaluation, three commercial products manufactured by different processes were selected and placed at 30°C/75%RH to simulate in use condition. Samples were withdrawn up to 12 weeks and analyzed for the physicochemical changes. Scanning electron microscopy demonstrated increasing holes and craters in the tablets over the timeframe. Near-infrared chemical imaging and powder X-ray powder diffraction corroborated the change arising from conversion of crystalline to amorphous forms of the drug. Hardness and disintegration time of the tablets were found to increase progressively. With increasing time, moisture contents of the products were found to increase and consequent decrease in isopropyl alcohol content of the product. Dissolution of the tablets in media at pH 4.5 demonstrated discrimination between crystalline and amorphous drug products. Overall, percent drug dissolved in each product at 30 min was found to decrease with increasing exposure time. Dissolution of drug decreased from 54% to 38% and 82% to 54% for the two products while the third product maintained consistently high level of dissolution. These results suggest that the drug product quality attributes can change during use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. [Evaluation of drug addicts with associated pathology. Clinical and therapeutic aspects of the integral attention].

    Science.gov (United States)

    Muga, Roberto; Guardiola, Helena; Rey-Joly, Celestino

    2004-05-01

    We review the evaluation and treatment of patients with drug addictions complicated by other acute or chronic diseases from the perspective of the hospital setting. The spectrum of drug addiction's complications is broad and in many instances it is predetermined by the abuse substance and its administration route. Some complications of intravenous drug addiction have dramatically decreased in the last few years as a result of a better knowledge of hygienic customs and after the implementation of some health interventions such as the provision of sterile injectable devices. Two highly prevalent infections --HIV/AIDS and hepatitis C-- remain from the period in which most HIV infections owed to the intravenous use of heroin. Of note, these two infections largely account for the survival and quality of life of those who quit their addiction. On the other hand, it is still common the hospitalization of patients with both alcohol dependence and intercurrent diseases in whom their drug addiction may pass unnoticed. Other common situations include the treatment of acute patients with cocaine addiction and psychiatric comorbidity, patients under methadone therapy and, in general, all those cases in which, in emergency, ordinary hospital wards and specialized units, a wide differential diagnosis is raised when there is a coexistence of signs and symptoms common to an addiction, infection and/or intoxication. An integral vision of drug addiction and its complications, as well as the clinical evaluation of all health problems, is fundamental for the prognosis and treatment of these patients.

  18. Development and evaluation of 'Pure Rush': An online serious game for drug education.

    Science.gov (United States)

    Stapinski, Lexine A; Reda, Bill; Newton, Nicola C; Lawler, Siobhan; Rodriguez, Daniel; Chapman, Catherine; Teesson, Maree

    2018-04-01

    Learning is most effective when it is active, enjoyable and incorporates feedback. Past research demonstrates that serious games are prime candidates to utilise these principles, however the potential benefits of this approach for delivering drug education are yet to be examined in Australia, a country where drug education in schools is mandatory. The serious game 'Pure Rush' was developed across three stages. First, formative consultation was conducted with 115 students (67% male, aged 15-17 years), followed by feasibility and acceptability testing of a prototype of the game (n = 25, 68% male). In the final stage, 281 students (62% female, aged 13-16 years) were randomly allocated to receive a lesson involving Pure Rush or an active control lesson. The lessons were compared in terms of learning outcomes, lesson engagement and future intentions to use illicit drugs. Students enjoyed playing Pure Rush, found the game age-appropriate and the information useful to them. Both the Pure Rush and the active control were associated with significant knowledge increase from pre to post-test. Among females, multi-level mixed-effects regression showed knowledge gain was greater in the Pure Rush condition compared to control (β = 2.36, 95% confidence interval 0.36-4.38). There was no evidence of between condition differences in lesson engagement or future intentions to use illicit drugs. Pure Rush is an innovative online drug education game that is well received by students and feasible to implement in schools. [Stapinski LA, Reda B, Newton NC, Lawler S, Rodriguez D, Chapman C, Teesson M. Development and evaluation of 'Pure Rush': An online serious game for drug education. Drug Alcohol Rev 2017]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  19. Development, optimization and evaluation of polymeric electrospun nanofiber: A tool for local delivery of fluconazole for management of vaginal candidiasis.

    Science.gov (United States)

    Sharma, Rahul; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    The present study is designed to explore the localized delivery of fluconazole using mucoadhesive polymeric nanofibers. Drug-loaded polymeric nanofibers were fabricated by the electrospinning method using polyvinyl alcohol (PVA) as the polymeric constituent. The prepared nanofibers were found to be uniform, non-beaded and non-woven, with the diameter of the fibers ranging from 150 to 180 nm. Further drug release studies indicate a sustained release of fluconazole over a period of 6 h. The results of studies on anti-microbial activity indicated that drug-loaded polymeric nanofibers exhibit superior anti-microbial activity against Candida albicans, when compared to the plain drug.

  20. Linear-scaling evaluation of the local energy in quantum Monte Carlo

    International Nuclear Information System (INIS)

    Austin, Brian; Aspuru-Guzik, Alan; Salomon-Ferrer, Romelia; Lester, William A. Jr.

    2006-01-01

    For atomic and molecular quantum Monte Carlo calculations, most of the computational effort is spent in the evaluation of the local energy. We describe a scheme for reducing the computational cost of the evaluation of the Slater determinants and correlation function for the correlated molecular orbital (CMO) ansatz. A sparse representation of the Slater determinants makes possible efficient evaluation of molecular orbitals. A modification to the scaled distance function facilitates a linear scaling implementation of the Schmidt-Moskowitz-Boys-Handy (SMBH) correlation function that preserves the efficient matrix multiplication structure of the SMBH function. For the evaluation of the local energy, these two methods lead to asymptotic linear scaling with respect to the molecule size

  1. Evaluation of local site effect from microtremor measurements in Babol City, Iran

    Science.gov (United States)

    Rezaei, Sadegh; Choobbasti, Asskar Janalizadeh

    2018-03-01

    Every year, numerous casualties and a large deal of financial losses are incurred due to earthquake events. The losses incurred by an earthquake vary depending on local site effect. Therefore, in order to conquer drastic effects of an earthquake, one should evaluate urban districts in terms of the local site effect. One of the methods for evaluating the local site effect is microtremor measurement and analysis. Aiming at evaluation of local site effect across the city of Babol, the study area was gridded and microtremor measurements were performed with an appropriate distribution. The acquired data was analyzed through the horizontal-to-vertical noise ratio (HVNR) method, and fundamental frequency and associated amplitude of the H/V peak were obtained. The results indicate that fundamental frequency of the study area is generally lower than 1.25 Hz, which is acceptably in agreement with the findings of previous studies. Also, in order to constrain and validate the seismostratigraphic model obtained with this method, the results were compared with geotechnical, geological, and seismic data. Comparing the results of different methods, it was observed that the presented geophysical method can successfully determine the values of fundamental frequency across the study area as well as local site effect. Using the data obtained from the analysis of microtremor, a microzonation map of fundamental frequency across the city of Babol was prepared. This map has numerous applications in designing high-rise building and urban development plans.

  2. Evaluating local and overall thermal comfort in buildings using thermal manikins

    Energy Technology Data Exchange (ETDEWEB)

    Foda, E.

    2012-07-01

    Evaluation methods of human thermal comfort that are based on whole-body heat balance with its surroundings may not be adequate for evaluations in non-uniform thermal conditions. Under these conditions, the human body's segments may experience a wide range of room physical parameters and the evaluation of the local (segmental) thermal comfort becomes necessary. In this work, subjective measurements of skin temperature were carried out to investigate the human body's local responses due to a step change in the room temperature; and the variability in the body's local temperatures under different indoor conditions and exposures as well as the physiological steady state local temperatures. Then, a multi-segmental model of human thermoregulation was developed based on these findings to predict the local skin temperatures of individuals' body segments with a good accuracy. The model predictability of skin temperature was verified for steady state and dynamic conditions using measured data at uniform neutral, cold and warm as well as different asymmetric thermal conditions. The model showed very good predictability with average absolute deviation ranged from 0.3-0.8 K. The model was then implemented onto the control system of the thermal manikin 'THERMINATOR' to adjust the segmental skin temperature set-points based on the indoor conditions. This new control for the manikin was experimentally validated for the prediction of local and overall thermal comfort using the equivalent temperature measure. THERMINATOR with the new control mode was then employed in the evaluation of localized floor-heating system variants towards maximum energy efficiency. This aimed at illustrating a design strategy using the thermal manikin to find the optimum geometry and surface area of a floor-heater for a single seated person. Furthermore, a psychological comfort model that is based on local skin temperature was adapted for the use with the model of human

  3. Flow cytometry for the evaluation of anti-plasmodial activity of drugs on Plasmodium falciparum gametocytes

    Directory of Open Access Journals (Sweden)

    Pipy Bernard

    2010-02-01

    Full Text Available Abstract Background The activity of promising anti-malarial drugs against Plasmodium gametocytes is hard to evaluate even in vitro. This is because visual examination of stained smears, which is commonly used, is not totally convenient. In the current study, flow cytometry has been used to study the effect of established anti-malarial drugs against sexual stages obtained from W2 strain of Plasmodium falciparum. Gametocytes were treated for 48 h with different drug concentrations and the gametocytaemia was then determined by flow cytometry and compared with visual estimation by microscopy. Results and conclusions Initially gametocytaemia was evaluated either using light microscopy or flow cytometry. A direct correlation (r2 = 0.9986 was obtained. Two distinct peaks were observed on cytometry histograms and were attributed to gametocyte populations. The activities of established anti-malarial compounds were then measured by flow cytometry and the results were equivalent to those obtained using light microscopy. Primaquine and artemisinin had IC50 of 17.6 μM and 1.0 μM, respectively. Gametocyte sex was apparently distinguishable by flow cytometry as evaluated after induction of exflagellation by xanthurenic acid. These data form the basis of further studies for developing new methods in drug discovery to decrease malaria transmission.

  4. Chemometric approach to evaluate heavy metals’ content in Daucus Carota from different localities in Serbia

    Directory of Open Access Journals (Sweden)

    Mitic Violeta D.

    2015-01-01

    Full Text Available The aim of this study was to evaluate heavy metal content in carrots (Daucus carota from the different localities in Serbia and assess by the cluster analysis (CA and principal components analysis (PCA the heavy metal contamination of carrots from these areas. Carrot was collected at 13 locations in five districts. Chemometric methods (CA and PCA were applied to classify localities according to heavy metal content in carrots. CA separated localities into two statistical significant clusters. PCA permitted the reduction of 12 variables to four principal components explaining 79.94% of the total variance. The first most important principal component was strongly associated with the value of Cu, Sb, Pb and Tl. This study revealed that CA and PCA appear useful tools for differentiation of localities in different districts using the profile of heavy metal in carrot samples. [Projekat Ministarstva nauke Republike Srbije, br. 172051

  5. 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 ...

  6. An Evaluation of The Effects of Local Mix Design on the ...

    African Journals Online (AJOL)

    This is a report on an evaluation of the effect of local mix design of concrete on its compressive strength. In order to accomplish this research work, field survey was first undertaken with a well-structured questionnaire. This questionnaire was administered to the respondents who are directly involved in concrete production.

  7. Evaluation of a Florida coastal golf complex as a local and watershed source of bioavailable contaminants

    Science.gov (United States)

    Lewis, Michael A., Robert L. Quarles, Darrin D. Dantin and James C. Moore. 2004. Evaluation of a Coastal Golf Complex as a Local and Watershed Source of Bioavailable Contaminants. Mar. Pollut. Bull. 48(3-4):254-262. (ERL,GB 1183). Contaminant fate in coastal areas impacte...

  8. Local electrochemical evaluation of a self-healing coating based on encapsulated healing-agent

    NARCIS (Netherlands)

    González-García, Y.; García, S.J.; Fischer, H.R.; Hughes, A.E.; Mol, J.M.C.

    2011-01-01

    In this work local electrochemical techniques are introduced as powerful and complementary techniques for the in-situ evaluation of self-healing systems applied for the protection of metals against corrosion. Scanning vibrating electrode technique (SVET) and scanning electrochemical microscopy

  9. Evaluation of rational drug use based on World Health Organization core drug use indicators in selected public hospitals of eastern Ethiopia: a cross sectional study.

    Science.gov (United States)

    Sisay, Mekonnen; Mengistu, Getnet; Molla, Bereket; Amare, Firehiwot; Gabriel, Tesfaye

    2017-02-23

    Despite the complexity of drug use, a number of indicators have been developed, standardized and evaluated by the World Health Organization (WHO). These indicators are grouped in to three categories namely: prescribing indicators, patient care indicators and facility indicators. The study was aimed to evaluate rational drug use based on WHO-core drug use indicators in Dilchora referral hospital, Dire Dawa; Hiwot Fana specialized university hospital, Harar and Karamara general hospital, Jigjiga, eastern Ethiopia. Hospital based quantitative cross sectional study design was employed to evaluate rational drug use based on WHO core drug use indicators in selected hospitals. Systematic random sampling for prescribing indicators and convenient sampling for patient care indicators was employed. Taking WHO recommendations in to account, a total of 1,500 prescription papers (500 from each hospitals) were investigated. In each hospital, 200 outpatient attendants and 30 key essential drugs were also selected using the WHO recommendation. Data were collected using retrospective and prospective structured observational check list. Data were entered to EPI Data Version 3.1, exported and analyzed using SPSS version 16.0. Besides, the data were evaluated as per the WHO guidelines. Statistical significance was determined by one way analysis of variance (ANOVA) for some variables. P-value of less than 0.05 was considered statistically significant. Finally, tabular presentation was used to present the data. Mean, 2.34 (±1.08) drugs were prescribed in the selected hospitals. Prescriptions containing antibiotics and that of injectables were 57.87 and 10.9% respectively. The average consultation and dispensing time were 276.5 s and 61.12 s respectively. Besides, 75.77% of the prescribed drugs were actually dispensed. Only 3.3% of prescriptions were adequately labeled and 75.7% patients know about the dosage of the prescription. Not more than, 20(66.7%) key drugs were available in

  10. Driving under the influence of drugs -- evaluation of analytical data of drugs in oral fluid, serum and urine, and correlation with impairment symptoms.

    Science.gov (United States)

    Toennes, Stefan W; Kauert, Gerold F; Steinmeyer, Stefan; Moeller, Manfred R

    2005-09-10

    A study was performed to acquire urine, serum and oral fluid samples in cases of suspected driving under the influence of drugs of abuse. Oral fluid was collected using a novel sampling/testing device (Dräger DrugTest System). The aim of the study was to evaluate oral fluid and urine as a predictor of blood samples positive for drugs and impairment symptoms. Analysis for cannabinoids, amphetamine and its derivatives, opiates and cocaine was performed in urine using the Mahsan Kombi/DOA4-test, in serum using immunoassay and gas chromatography-mass spectrometry (GC-MS) confirmation and in oral fluid by GC-MS. Police and medical officer observations of impairment symptoms were rated and evaluated using a threshold value for the classification of driving inability. Accuracy in correlating drug detection in oral fluid and serum were >90% for all substances and also >90% in urine and serum except for THC (71.0%). Of the cases with oral fluid positive for any drug 97.1% of corresponding serum samples were also positive for at least one drug; of drug-positive urine samples this were only 82.4%. In 119 of 146 cases, impairment symptoms above threshold were observed (81.5%). Of the cases with drugs detected in serum, 19.1% appeared not impaired which were the same with drug-positive oral fluid while more persons with drug-positive urine samples appeared uninfluenced (32.7%). The data demonstrate that oral fluid is superior to urine in correlating with serum analytical data and impairment symptoms of drivers under the influence of drugs of abuse.

  11. Parent Engagement in Youth Drug Prevention in Chinese Families: Advancement in Program Development and Evaluation

    Directory of Open Access Journals (Sweden)

    Sandra K. M. Tsang

    2011-01-01

    Full Text Available The escalating youth drug abuse problem in Hong Kong has attracted intense attention from the government, schools, and youth service professionals. Most preventive efforts have focused directly on positive youth development, very often through school programs delivered to secondary school students. There have been limited efforts to engage parents even though it is obvious that the family is actually the primary context of children and youth development. This paper will assert the importance of parental engagement in youth drug-prevention work, discuss some barriers in such parental involvement, present some promising local attempts and their strengths and limitations, and propose that sustained efforts are needed to build up theory-driven and evidence-based resources for Chinese communities on the subject.

  12. Preparation and evaluation of bioadhesive benzocaine gels for enhanced local anesthetic effects.

    Science.gov (United States)

    Shin, Sang-Chul; Lee, Jin-Woo; Yang, Kyu-Ho; Lee, Chi H

    2003-07-09

    This study was performed to develop new enhanced anesthetic benzocaine gels with a suitable bioadhesive property for local anesthetic effects. As the concentration of benzocaine in the HPMC gels increased up to 15%, the permeation of drug increased, thereafter slightly increased. The activation energy of drug permeation was 11.29 kcal/mol. Bioadhesive forces were also measured. The permeation rate of drug through the skin was studied using various enhancers, such as glycols, non-ionic surfactants or fatty acids. Among the enhancers used, diethylene glycol showed the most enhancing effects. Analgesic activity was examined using a tail-flick analgesimeter. According to the rat tail-flick test, the value of AUEC (0 - 360min) of 15% benzocaine gels containing diethylene glycol was 4662 +/- 200 s min, while that of gels without diethylene glycol was 3353 +/- 132 s min, showing about 1.39-fold increase in analgesic activity. Fifteen percentage of benzocaine gels containing diethylene glycol showed the most enhanced, prolonged analgesic effects, showing the maximum anesthetic effects at 240 min, while the gels without diethylene glycol showed maximum effect at 180 min.

  13. Evaluation as a critical factor of success in local public health accreditation programs.

    Science.gov (United States)

    Tremain, Beverly; Davis, Mary; Joly, Brenda; Edgar, Mark; Kushion, Mary L; Schmidt, Rita

    2007-01-01

    This article presents the variety of approaches used to conduct evaluations of performance improvement or accreditation systems, while illustrating the complexity of conducting evaluations to inform local public health practice. We, in addition, hope to inform the Exploring Accreditation Program about relevant experiences involving accreditation and performance assessment processes, specifically evaluation, as it debates and discusses a national voluntary model. A background of each state is given. To further explore these issues, interviews were conducted with each state's evaluator to gain more in-depth information on the many different evaluation strategies and approaches used. On the basis of the interviews, the authors provide several overall themes, which suggest that evaluation is a critical tool and success factor for performance assessment or accreditation programs.

  14. Hazardous drug residue on exterior vial surfaces: evaluation of a commercial manufacturing process.

    Science.gov (United States)

    Power, Luci A; Sessink, Paul J M; Gesy, Kathy; Charbonneau, Flay

    2014-04-01

    Hazardous drug residue on the exterior surface of drug vials poses a potential risk for exposure of health care workers involved in handling these products. The purpose of this article is to heighten the awareness of this serious issue and to evaluate a commercial manufacturing process for removing and containing hazardous drug (HD) residue on exterior vial surfaces. Additionally, findings from this study are interpreted, incorporated into the current body of evidence, and discussed by experts in this field. This study includes separate evaluations for the presence or absence of surface drug contamination on the vials of 3 HD products: 5-fluorouracil, cisplatin, and methotrexate. The drug products were packaged in vials using a patented prewashing/decontamination method, application of a polyvinylchloride (PVC) base, and use of clear glass vials. An additional step of encasing the vial in a shrink-wrapped sheath was used for 5-fluorouracil and cisplatin. Of all 5-fluorouracil (110 vials), methotrexate (60 vials), and cisplatin (60 vials) tested, only 2 had detectable amounts of surface residue. One 5-fluorouracil vial was found to have approximately 4 mg of 5-fluorouracil on the surface of the vial. The second contaminated vial was cisplatin, which was discovered to have 131 ng of platinum, equal to 200 ng of cisplatin or 0.2 μL of cisplatin solution, on the vial sheath. Using validated extraction and analytic methods, all but 2 of the 230 tested vials were found to be free of surface drug contamination. Pharmacy leaders need to take an active role in promoting the need for clean HD vials. Manufacturers should be required to provide their clients with data derived from externally validated analytic studies, reporting the level of HD contamination on the exterior of their vial products.

  15. [Evaluation of the medical value of a drug. A necessity for the Transparency Commission].

    Science.gov (United States)

    Avouac, B

    1992-01-01

    The marketing approval (AMM) is based on criteria of pharmaceutical quality, efficacy and safety of use. Before marketing, the data are collected by means of double-blind, randomized, prospective clinical trials that compare the study product to a reference product. A post-AMM assessment is needed to define the increase of the medical benefit (ASMR) and the therapeutic value of the new drugs. The quantification of the ASMR is essential for registration on the list of drugs reimbursable for those who benefit from Social Security. The evaluation of the therapeutic value and the nature of the affection treated are the criteria upon which the reimbursement ratio is chosen. After marketing, the reevaluation of the medical benefit and the drugs' usefulness may be compared to the treatment's net medical cost (direct + indirect cost--avoided cost) in cost/utility or cost/benefit studies. The Transparency Commission has worked out a scale of assessment of the ASMR which will orient recommendation, or non-recommendation, of registration on the list of reimbursable drugs as well as price fixing proposals. In the future, the Transparency Commission is to strengthen its position regarding the good use of the drug through a better prescriber information system. Thanks to the pharmaco-epidemiology and the pharmaco-vigilance data, the Transparency Commission will be able to guarantee the post-marketing follow-up of the drugs. The examination of the products' conditions of use, the reevaluation of the treatment's advantages based on the utility studies and the epidemiological surveys, and the cost-benefit studies will contribute to a medical control of health spending linked to drug consumption.

  16. A controlled evaluation of family behavior therapy in concurrent child neglect and drug abuse.

    Science.gov (United States)

    Donohue, Brad; Azrin, Nathan H; Bradshaw, Kelsey; Van Hasselt, Vincent B; Cross, Chad L; Urgelles, Jessica; Romero, Valerie; Hill, Heather H; Allen, Daniel N

    2014-08-01

    Approximately 50% of child protective service (CPS) referrals abuse drugs; yet, existing treatment studies in this population have been limited to case examinations. Therefore, a family-based behavioral therapy was evaluated in mothers referred from CPS for child neglect and drug abuse utilizing a controlled experimental design. Seventy-two mothers evidencing drug abuse or dependence and child neglect were randomly assigned to family behavior therapy (FBT) or treatment as usual (TAU). Participants were assessed at baseline, 6 months, and 10 months postrandomization. As hypothesized, intent-to-treat repeated measures analyses revealed mothers referred for child neglect not due to their children being exposed to illicit drugs demonstrated better outcomes in child maltreatment potential from baseline to 6- and 10-month postrandomization assessments when assigned to FBT, as compared with TAU mothers and FBT mothers who were referred due to child drug exposure. Similar results occurred for hard drug use from baseline to 6 and 10 months postrandomization. However, TAU mothers referred due to child drug exposure were also found to decrease their hard drug use more than TAU mothers of non-drug-exposed children and FBT mothers of drug-exposed children at 6 and 10 months postrandomization. Although effect sizes for mothers assigned to FBT were slightly larger for marijuana use than TAU (medium vs. large), these differences were not statistically significant. Specific to secondary outcomes, mothers in FBT, relative to TAU, increased time employed from baseline to 6 and 10 months postrandomization. Mothers in FBT, compared to TAU, also decreased HIV risk from baseline to 6 months postrandomization. There were no differences in outcome between FBT and TAU for number of days children were in CPS custody and alcohol intoxication, although FBT mothers demonstrated marginal decreases (p = .058) in incarceration from baseline to 6 months postrandomization relative to TAU mothers

  17. Feasibility of abdominal plain film images in evaluation suspected drug smuggler

    Energy Technology Data Exchange (ETDEWEB)

    Sormaala, Markus J., E-mail: markus.sormaala@welho.com [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Salonen, Hanna-Mari, E-mail: hanna-mari.salonen@hus.fi [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Mattila, Ville M., E-mail: ville.mattila@uta.fi [Department of Orthopedic Surgery and Trauma, Tampere University Hospital, Tampere (Finland); Kivisaari, Arto, E-mail: arto.kivisaari@hus.fi [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Autti, Taina, E-mail: taina.autti@hus.fi [Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland)

    2012-09-15

    Objective: Drug smuggling in the gastrointestinal tract has soared within the last 20 years. Though illegal substances in the gastrointestinal tract can be visualized with ultrasound, MRI and CT, the abdominal radiograph has by far remained the most frequently used way of detecting smuggled drugs. The purpose of the study was to evaluate the inter-radiologist interpretation error and the reliability of the abdominal radiograph in detecting smuggled drugs. Materials and methods: A total of 279 abdominal radiographs of suspected smugglers were classified by three radiologists as clearly positive or negative for drug smuggling. All available information about the cases was collected from the customs officers and police. Results: Out of these cases 203 (73%) were interpreted as negative and 35 (13%) as positive by all three radiologists. In 86% of the cases there was, therefore, an inter-radiological agreement in interpreting the images. In 41 (14%) cases, however, there was an inter-radiologist disagreement. Kappa-value for inter-observer variability was 0.70. Conclusions: In up to a seventh of the abdominal radiographs the interpretation can be challenging even for an experienced radiologist. False positive interpretation can lead to innocent passengers being detained in vain. As negatively interpreted images usually result in releasing of the suspect, there is no way of knowing how many false negative occur. This makes the abdominal radiograph a suboptimal examination, and low dose CT should be considered as the screening modality for gastrointestinal drug smugglers.

  18. Feasibility of abdominal plain film images in evaluation suspected drug smuggler

    International Nuclear Information System (INIS)

    Sormaala, Markus J.; Salonen, Hanna-Mari; Mattila, Ville M.; Kivisaari, Arto; Autti, Taina

    2012-01-01

    Objective: Drug smuggling in the gastrointestinal tract has soared within the last 20 years. Though illegal substances in the gastrointestinal tract can be visualized with ultrasound, MRI and CT, the abdominal radiograph has by far remained the most frequently used way of detecting smuggled drugs. The purpose of the study was to evaluate the inter-radiologist interpretation error and the reliability of the abdominal radiograph in detecting smuggled drugs. Materials and methods: A total of 279 abdominal radiographs of suspected smugglers were classified by three radiologists as clearly positive or negative for drug smuggling. All available information about the cases was collected from the customs officers and police. Results: Out of these cases 203 (73%) were interpreted as negative and 35 (13%) as positive by all three radiologists. In 86% of the cases there was, therefore, an inter-radiological agreement in interpreting the images. In 41 (14%) cases, however, there was an inter-radiologist disagreement. Kappa-value for inter-observer variability was 0.70. Conclusions: In up to a seventh of the abdominal radiographs the interpretation can be challenging even for an experienced radiologist. False positive interpretation can lead to innocent passengers being detained in vain. As negatively interpreted images usually result in releasing of the suspect, there is no way of knowing how many false negative occur. This makes the abdominal radiograph a suboptimal examination, and low dose CT should be considered as the screening modality for gastrointestinal drug smugglers

  19. Evaluating the administration costs of biologic drugs: development of a cost algorithm.

    Science.gov (United States)

    Tetteh, Ebenezer K; Morris, Stephen

    2014-12-01

    Biologic drugs, as with all other medical technologies, are subject to a number of regulatory, marketing, reimbursement (financing) and other demand-restricting hurdles applied by healthcare payers. One example is the routine use of cost-effectiveness analyses or health technology assessments to determine which medical technologies offer value-for-money. The manner in which these assessments are conducted suggests that, holding all else equal, the economic value of biologic drugs may be determined by how much is spent on administering these drugs or trade-offs between drug acquisition and administration costs. Yet, on the supply-side, it seems very little attention is given to how manufacturing and formulation choices affect healthcare delivery costs. This paper evaluates variations in the administration costs of biologic drugs, taking care to ensure consistent inclusion of all relevant cost resources. From this, it develops a regression-based algorithm with which manufacturers could possibly predict, during process development, how their manufacturing and formulation choices may impact on the healthcare delivery costs of their products.

  20. EVALUATION OF THE PREVALENCE OF THE PERIODONTAL DISEASE VERSUS SYSTEMIC AND LOCAL RISK FACTORS

    Directory of Open Access Journals (Sweden)

    Silvia MÂRŢU

    2013-07-01

    Full Text Available Introduction: The periodontal disease represents a malady characterized by an extremely high incidence. The manifestations and evolution of the periodontal diseases vary for each form in part, being influenced by systemic and local risk factors. Scope of the study: To evaluate the periodontal status on a group of patients, versus the syste‐ mic and local factors. Materials and method: The study was performed on a group of 170 patients, whose odonto‐periodontal status was evaluated by strict clinical and paraclinical examinations, on establishing the inflammation indices and the periodontal diagnosis. Results: The main cause of the analysis was gingival ble‐ eding; an increased number of smokers was registered among the patients. Out of the local factors, especially important were edentations and malocclusions. Also, a higher number of aggressive generalized periodontites has been noticed. Discussion: The forms of the periodontal diseases are obviously influenced by the systemic context, while the forms of localized chronic periodontitis associa‐ ted with generalized chronic gingivitis reflect the role pla‐ yed by the local risk factors. Conclusions: Stress and smoking represent significant risk factors in the installation of periodontal pathology, with a really alarming preva‐ lence. The aggressive forms of periodontitis showed a higher frequency than that recorded in literature.

  1. ULTRACAVITATION METHOD OF EVALUATION IN THE REDUCTION OF LOCALIZED FAT IN WOMEN

    Directory of Open Access Journals (Sweden)

    L. Petraglia

    2017-02-01

    Full Text Available This study evaluated cosmetic fat reduction methods that cause localized lipolysis and that are not invasive. The use of a differentiated ultrasound called Ultracavitation was evaluated, it causes reduction of localized fat in the infra abdominal region. 30 women aged 30-45 years old, healthy, sedentary were evaluated; they were separated into two groups subjected to 12 treatment sessions in infra abdominal region, once a week, alone or combined with aerobic exercise. Photographic recording was performed for comparison, determining the infra abdominal circumference and the amount of glycerol in urine samples of the participants, which was measured via reactions catalyzed by glycerol kinase, glycerol phosphate oxidase and peroxidase enzymes. The use of Ultracavitation associated with the treadmill or without it had a relevant result. The measurement of glycerol in the urine samples did not present statistically a significant result.

  2. Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

    Science.gov (United States)

    Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

    2018-01-01

    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

  3. Is Project Towards No Drug Abuse (Project TND) an evidence-based drug and violence prevention program? A review and reappraisal of the evaluation studies.

    Science.gov (United States)

    Gorman, Dennis M

    2014-08-01

    This paper critically reviews the published evidence pertaining to Project Towards No Drug Abuse (Project TND). Publications from seven evaluation studies of Project TND are reviewed, and the results from these are discussed as related to the following outcomes: main effects on the use of cigarettes, alcohol and marijuana; main effects on the use of "hard drugs," defined in the evaluations as cocaine, hallucinogens, stimulants, inhalants, ecstasy and other drugs (e.g., depressants, PCP, steroids and heroin); subgroup and interaction analyses of drug use; and violence-related behaviors. Very few main effects have been found for cigarette, alcohol and marijuana use in the Project TND evaluations. While studies do report main effects for hard drug use, these findings are subject to numerous threats to validity and may be attributable to the data analyses employed. Similarly, while isolated subgroup and interaction effects were found for alcohol use among baseline nonusers and some violence-related behaviors in the early Project TND evaluations, these findings have not been replicated in more recent studies and may result from multiple comparisons between study conditions. In conclusion, there is little evidence to support the assertion that Project TND is an effective drug or violence prevention program. The broader implications of these findings for prevention science are discussed and suggestions are made as to how the quality of research in the field might be improved.

  4. Illicit drug exposure in patients evaluated for alleged child abuse and neglect.

    Science.gov (United States)

    Oral, Resmiye; Bayman, Levent; Assad, Abraham; Wibbenmeyer, Lucy; Buhrow, Jakob; Austin, Andrea; Bayman, Emine O

    2011-06-01

    Substantiation of drug exposure in cases with alleged maltreatment is important to provide proper treatment and services to these children and their families. A study performed at University of Iowa Hospitals and Clinics showed that 30% of pediatric patients with burn injuries, which were due to child maltreatment, were also exposed to illicit drugs. The children presenting to the University of Iowa Hospitals and Clinics with alleged maltreatment have been tested for illicit substances since 2004. The objective of this study was to analyze the presence of illicit drug exposure in the pediatric subpopulation admitted to pediatric inpatient and outpatient units for an evaluation for abuse/neglect. The study design is a retrospective chart review. Using hospital databases, every pediatric chart with a child abuse/neglect allegation was retrieved. The association between risk factors and clinical presentation and illicit drug test result was assessed. Excel and SAS were used for statistical analysis. Institutional review board approval was obtained to conduct this study. Six hundred sixty-five charts met study inclusion criteria for child abuse/neglect allegation. Of those, 232 cases were tested for illicit drugs between 2004 and 2008 per the testing protocol. Thirty-four cases (14.7%) tested positive on a drug test. Positive test rates based on clinical presentation were 28.6% (18/63) in neglect cases, 16.1% (5/31) in cases with soft tissue injuries, 14.3% (4/28) in burn injuries, 10.0% (2/20) in cases with sexual abuse, 7.1% (2/28) in cases with fractures, and 4.8% (3/62) in abusive head trauma cases. There were long-term abuse findings in 129 children (55.6%). Logistic regression analysis revealed that positive drug testing was most significantly associated with clinical symptoms suggesting physical abuse or neglect versus sexual abuse (odds ratio [OR] = 6.70; 95% confidence interval [CI], 1.26-35.49; P = 0.026), no or public health insurance versus those with

  5. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Kunio Yoshizawa

    2016-01-01

    Full Text Available A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

  6. Evaluation of local allowable wall thickness of thinned pipe considering internal pressure and bending moment

    International Nuclear Information System (INIS)

    Kim, J. W.; Park, C. Y.; Kim, B. Y.

    2000-01-01

    This study proposed the local allowable wall thickness (LAWT) evaluation method for local wall thinned pipe subjected by internal pressure and bending moment. Also, LAWT was evaluated for simplified thinned pipe and the effect of axial extent of thinned area on LAWT was investigated. The results showed that LAWT predicted by present method was thinner, about 50%, than that evaluated by construction code and ASME Code Case N-597, while it was thicker, about 2 times, than that calculated by evaluation model based on pipe experiments. LAWT decreased with increasing axial extent of thinned area and was saturated above axial extent of pipe radius, which was a contrast to the results of ASME Code Case N-597 evaluation. The results of stress analysis with applied loading type indicated that the effect of axial extent of thinned area on LAWT was dependent on loading type considering in the evaluation. That is, the dependence of axial extent on LAWT is determined by magnitude of bending moment, and the contrary trend with axial extent in ASME Code Case is because ASME Code Case N-597 considers only internal pressure in the evaluation

  7. Evaluation of dressings used with local anaesthetic cream and for peripheral venous cannulation.

    Science.gov (United States)

    Needham, Rowan; Strehle, Eugen-Matthias

    2008-10-01

    To compare four polyurethane dressings manufactured by two different companies for use in children. Seventy-eight dressings were applied to secure either local anaesthetic creams (n = 62) or intravenous cannulae (n = 16). Each dressing was evaluated for ease of application, security and ease of removal, using a simple scoring system. 84 per cent of Opsite flexigrid and 90 per cent of Tegaderm local anaesthetic cream dressings were rated as easy or very easy to apply. Opsite flexigrid was felt to be more secure, whereas Tegaderm was easier to remove. The Tegaderm cannula dressing was easier to apply than the iv3000 dressing. There was little difference between the two brands, including costs.

  8. Evaluating the accuracy of perfusion/metabolism (SPET/PET) ratio in seizure localization

    Energy Technology Data Exchange (ETDEWEB)

    Buch, K.; Zubal, I.G. [Yale School of Medicine, Department of Diagnostic Radiology, New Haven, CT (United States); Blumenfeld, H.; Spencer, S.; Novotny, E. [Yale School of Medicine, Department of Neurology, P.O. Box 208018, New Haven, CT (United States)

    2008-03-15

    The uncoupling between brain perfusion and metabolism was evaluated as a potential tool for seizure localization by creating an interictal SPET divided by interictal PET functional ratio-image and by evaluating its sensitivity and specificity to areas subsequently surgically resected. The uncoupling between brain perfusion and metabolism was evaluated through the creation of a functional SPET/PET ratio-image relying on interictal single-photon emission computed tomography (SPET) and positron emission tomography (PET) scans in epilepsy patients. The uncoupling of these two physiological brain functions has been demonstrated to be a characteristic of epileptogenic tissue in temporal lobe epilepsy and could potentially serve as a diagnostic measure for localization of seizure onset areas in the brain. The accuracy of hemispheric localization, sensitivity, and specificity of perfusion to metabolism ratio-images were evaluated as compared to standard methods of PET reading. Interictal HMPAO-SPET and FDG-PET scans were obtained from 21 patients who then went on to remain seizure free for a minimum of 1 year post surgical resection. Using Statistical Parametric Mapping (SPM2), the SPET and PET scans were spatially registered and spatially normalized to a standard template (geometric warping). A functional image was created by calculating the ratio of perfusion to metabolism. Discrete areas of uncoupling in the ratio-images were selected, quantified, and compared to visually interpreted PET readings as well as the actual site of subsequent surgical resection. Localization was determined by comparing the hemispheric location of these areas to sites of surgical resection. Sensitivity and specificity of ratio-images and PET readings were calculated by dividing the brains into four sections per hemisphere. When compared to known sites of successful surgical resection, the pre-surgical visually interpreted PET readings had a correct hemispheric localization in 69.6% of cases

  9. [Evaluation of the learning curve of residents in localizing a phantom target with ultrasonography].

    Science.gov (United States)

    Dessieux, T; Estebe, J-P; Bloc, S; Mercadal, L; Ecoffey, C

    2008-10-01

    Few information are available regarding the learning curve in ultrasonography and even less for ultrasound-guided regional anesthesia. This study aimed to evaluate in a training program the learning curve on a phantom of 12 residents novice in ultrasonography. Twelve trainees inexperienced in ultrasonography were given introductory training consisting of didactic formation on the various components of the portable ultrasound machine (i.e. on/off button, gain, depth, resolution, and image storage). Then, students performed three trials, in two sets of increased difficulty, at executing these predefined tasks: adjustments of the machine, then localization of a small plastic piece introduced into roasting pork (3 cm below the surface). At the end of the evaluation, the residents were asked to insert a 22 G needle into an exact predetermined target (i.e. point of fascia intersection). The progression of the needle was continuously controlled by ultrasound visualization using injection of a small volume of water (needle perpendicular to the longitudinal plane of the ultrasound beam). Two groups of two different examiners evaluated for each three trials the skill of the residents (quality, time to perform the machine adjustments, to localize the plastic target, and to hydrolocalize, and volume used for hydrolocalization). After each trial, residents evaluated their performance using a difficulty scale (0: easy to 10: difficult). All residents performed the adjustments from the last trial of each set, with a learning curve observed in terms of duration. Localization of the plastic piece was achieved by all residents at the 6th trial, with a shorter duration of localization. Hydrolocalization was achieved after the 4th trial by all subjects. Difficulty scale was correlated to the number of trials. All these results were independent of the experience of residents in regional anesthesia. Four trials were necessary to adjust correctly the machine, to localize a target, and to

  10. Parenting Styles as Correlates of Adolescents Drug Addiction among Senior Secondary School Students in Obio-Akpor Local Government Area of Rivers State, Nigeria

    Science.gov (United States)

    Onukwufor, Jonathan N.; Chukwu, Mercy Anwuri

    2017-01-01

    The study was conducted to find out the relationship between parenting styles and secondary students' drug addiction among adolescents in secondary schools in Obio-Akpor Local Government Area (L.G.A.) of Rivers State Nigeria. The study was guided by three research questions and similar number of null hypotheses. The study adopted a correlation…

  11. Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.

    Science.gov (United States)

    Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina

    2016-01-01

    To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers. An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods. Bupropion intake influenced all the pharmacokinetic parameters of both atomoxetine and its metabolite. For atomoxetine, Cmax increased from 226±96.1 to 386±137 ng/mL and more importantly, AUC0-∞ was significantly increasedfrom 1580±1040 to 8060±4160 ng*h/mL, while the mean t1/2 was prolonged after bupropion pretreatment. For 4-hydroxyatomoxetine-O-glucuronide, Cmax and AUC0-∞  were decreased from 707±269 to 212±145 ng/mL and from 5750±1240 to 3860±1220 ng*h/mL, respectively. These results demonstrated that the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite (1.5-fold). Additional studies are required in order to evaluate the clinical relevance of this pharmacokinetic drug interaction.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  12. The political and scientific challenges in evaluating compulsory drug treatment centers in Southeast Asia

    OpenAIRE

    Vuong, Thu; Nguyen, Nhu; Le, Giang; Shanahan, Marian; Ali, Robert; Ritter, Alison

    2017-01-01

    Background In Vietnam, like many countries in Southeast Asia, the commonly used approach of center-based compulsory drug treatment (CCT) has been criticized on human rights ground. Meanwhile, community-based voluntary methadone maintenance treatment (MMT) has been implemented for nearly a decade with promising results. Reform-minded leaders have been seeking empirical evidence of the costs and effectiveness associated with these two main treatment modalities. Conducting evaluations of these t...

  13. Evaluation of new drugs in daily clinical practice: anti-TNF alpha in rheumatoid arthritis patients.

    OpenAIRE

    Kievit, W.

    2008-01-01

    The objective of this thesis was to explore the value and the validity of data collected in daily clinical practice for drug evaluation and cost-effectiveness studies, using data collected on TNFa blocking agents in rheumatoid arthritis. First, the need for and value of information from daily clinical practice was researched. Together, the results of Chapters 3, 4 and 5 illustrated that treatment of RA patients with anti-TNFa blocking agents in daily clinical practice was different from what ...

  14. Piper betle LEAVES EXTRACT PATCH: EVALUATION OF ANTIBACTERIAL ACTIVITY, RELEASE PROFILE OF EUGENOL, AND LOCAL TOLERANCE

    Directory of Open Access Journals (Sweden)

    Mufrod Mufrod

    2016-08-01

    Full Text Available Piper betle leaf in extract form is more effective than crude drug. Eugenol is a component in the extract that has antibacterial activity but irritate. Patch of piper betle leaf extract was used on the mucosa to make oral cavity hygiene. Antibacterial activity was influenced by the release of eugenol from the patch. Release enhancer substances (RES such as glycerin, propylen glicol and tween 80 were added in patch formulation to increase the release of active substances. The aim of the research was to investigate the physicochemical properties, eugenol release profiles, and local tolerance test of the patch. Extract of piper betle leaf was made using infundation method. Patch was made according to the variation concentration of extract (1, 2 and 4% and RES (glycerine, propylen glycol and tween 80 using chitosan as vehicle. Patch produced solvent casting method. Patch obtained was tested for swelling index, folding endurance, surface pH, antibacterial activity, release of eugenol, and local tolerance. Data obtained were analyzed descriptively. The result showed that the addition of RES did not affect the surface pH but increase the water absorption with in inconsistent way except patch with tween 80. The flexibility (folding endurance value increased, and the highest amount of eugenol released was achieved by patch using propylen glicol. Patch with tween 80 and glycerin for all extract concentration and patch with 1% extract concentration using propylen glycol showed medium sensation (local tolerance, and patch with 2 and 4% extract using propylen glycol showed severe sensation.

  15. Evaluation of toxic heavy metals in ayurvedic syrups sold in local markets of hazara, pakistan

    International Nuclear Information System (INIS)

    Hajra, B.; Orakzai, S.; Hussain, F.; Farya, U.

    2015-01-01

    Herbal and Ayurvedic preparations, widely used in Pakistan and the developing world, present serious risk of heavy metal toxicity related to their medicinal content and prolonged use by patients. The objective of this study was to find out the concentration of heavy metals in Herbal and Ayurvedic liquid preparations commonly used for treatment of different diseases, from local markets of Hazara. Methods: The cross sectional survey of traditional herbal and Ayurvedic medicine shops included ten liquid preparations selected from local shops of Mansehra and Abbottabad after interviewing the shopkeepers; so as to select the most commonly sold preparations along with their indications. All samples were analysed on standard Atomic Absorption Spectroscopy for qualitative and quantitative study of toxic heavy metals (Mercury, Iron, Zinc, Lead, Manganese and Arsenic). Results: Toxic levels of Mercury were present in seven syrups, i.e., (Kashneeze, Akseer e Pachas, Tankar, Sharbat e folad, Urosinal, Akseer e Jigar and Amrat dhara) while Arsenic was present only in Urosinal. Iron, Zinc, Manganese and Lead were present in permissible limits in all syrups. Conclusion: Mercury and Arsenic are present in local Herbal and Ayurvedic liquid preparations far beyond the permissible limits as proposed by the International Regulatory Authorities for health drugs while the rest of metals, i.e., Zinc, Manganese, and Iron are within the therapeutic limits. (author)

  16. Evaluating the impact of Mexico's drug policy reforms on people who inject drugs in Tijuana, B.C., Mexico, and San Diego, CA, United States: a binational mixed methods research agenda.

    Science.gov (United States)

    Robertson, Angela M; Garfein, Richard S; Wagner, Karla D; Mehta, Sanjay R; Magis-Rodriguez, Carlos; Cuevas-Mota, Jazmine; Moreno-Zuniga, Patricia Gonzalez; Strathdee, Steffanie A

    2014-02-12

    collection procedures have been implemented successfully, demonstrating the importance of binational collaboration in evaluating the impact of structural-level drug policy reforms on the behaviors, health, and wellbeing of PWID across an international border. Our prospective, mixed methods approach allows each study to be responsive to emerging phenomena within local contexts while regular collaboration promotes sharing insights across studies. The strengths and limitations of this approach may serve as a guide for other evaluations of harm reduction policies internationally.

  17. [Effects of periodontal mechanical therapy with local and systemic drugs on carotid artery and serum high-sensitivity C-reactive protein in rats with chronic periodontitis associated with atherosclerosis].

    Science.gov (United States)

    Ren, Xiuyun; Chang, Le; Yue, Zijie; Lin, Mu; Shi, Xuexue; Sun, Lili

    2013-10-01

    The aim of this study is to investigate the effects of serum high-sensitivity C-reactive protein (hsCRP) and the pathological changes in the carotid artery after periodontal mechanical therapy with local and systemic drugs in SD rats with chronic periodontitis (CP) associated with atherosclerosis (As). Thirty-five SD rats were randomly divided into two groups: control group (group A) and CP+As group (group B). Group B was further divided into the natural process group (B1), the periodontal mechanical treatment group (B2), the periodontal mechanical treatment plus local drugs group (B3), and the periodontal mechanical treatment plus local and systemic drugs group (B4). Each group comprised seven rats. Serum hsCRP levels were evaluated at baseline 1 week after the first periodontal therapy and 1, 3, and 5 weeks after the second periodontal therapy by enzyme linked immunosorbent assay (ELISA). The pathological lesion in the carotid artery plaque was stained with hematine and eosin. The levels of serum hsCRP in group B1 increased gradually as time passed and became significantly higher than that of the other groups five weeks after periodontal therapy (P periodontal therapy. After that, the levels of serum hsCRP decreased gradually but were still higher than that of group A (P periodontal therapy (P periodontal mechanical treatment results in acute, short-term, systemic inflammation and might increase the risk of atherosclerosis in SD rats. However, the levels of serum hsCRP decreased gradually 3 to 5 weeks after therapy. With periodontal mechanical treatment, the benefits of local and systemic drugs are associated with improvement in atherosclerotic lesion progression.

  18. A computerized stroop test for the evaluation of psychotropic drugs in healthy participants.

    Science.gov (United States)

    Pilli, Raveendranadh; Naidu, Mur; Pingali, Usha Rani; Shobha, J C; Reddy, A Praveen

    2013-04-01

    The Stroop paradigm evaluates susceptibility to interference and is sensitive to dysfunction in frontal lobes and drug effects. The aim of the present study was to establish a simple and reliable computerized version of Stroop color-word test, which can be used for screening of various psychotropic drugs. The standardized method was followed in all cases, by recording the reaction time (RT) in msec in 24 healthy participants using computerized version of Stroop color-word test. Reproducibility of the test procedure was evaluated by recording the RTs by a single experimenter on two sessions (interday reproducibility). Validity of the model was further tested by evaluating the psychotropic effect of Zolpidem 5 mg, Caffeine 500 mg, or Placebo on 24 healthy subjects in a randomized, double blind three-way crossover design. The method was found to produce low variability with coefficient of variation less than 10%. Interday reproducibility was very good as shown by Bland-Altman plot with most of the values within ±2SD. There was a significant increase in RTs in Stroop performance with Zolpidem at 1 hr and 2 hrs; in contrast, caffeine significantly decreased RTs in Stroop performance at 1 hr only compared to placebo. The Stroop color-word recording and analysis system is simple, sensitive to centrally acting drug effects, and has potential for future experimental psychomotor assessment studies.

  19. Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

    International Nuclear Information System (INIS)

    Pentak, Danuta

    2016-01-01

    Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

  20. Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Pentak, Danuta, E-mail: danuta.pentak@us.edu.pl [University of Silesia, Department of Materials Chemistry and Chemical Technology, Institute of Chemistry (Poland)

    2016-05-15

    Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

  1. Comprehensive evaluation of carboxylated nanodiamond as a topical drug delivery system.

    Science.gov (United States)

    Lim, Dae Gon; Kim, Ki Hyun; Kang, Eunah; Lim, Sun Hee; Ricci, Jeremy; Sung, Si Kwon; Kwon, Myoung Taek; Jeong, Seong Hoon

    2016-01-01

    The best strategy in the development of topical drug delivery systems may be to facilitate the permeation of drugs without any harmful effects, while staying on the skin surface and maintaining stability of the system. Nanodiamonds (NDs) play a key role with their excellent physicochemical properties, including high biocompatibility, physical adsorption, reactive oxygen species (ROS) scavenging capability, and photostabilizing activity. Z-average sizes of carboxylated ND (ND-COOH) agglutinate decreased significantly as the pH increased. Fluorescein-conjugated ND was observed only on the stratum corneum, and no sample diffused into the dermal layer even after 48 hours. Moreover, ND-COOH and ND-COOH/eugenol complex did not show significant toxic effects on murine macrophage cells. ND improved in vitro skin permeation >50% acting as a "drug reservoir" to maintain a high drug concentration in the donor chamber, which was supported by quartz crystal microbalance results. Moreover, ND-COOH could adsorb a drug amount equivalent to 80% of its own weight. A photostability study showed that ND-COOH increased the photostability ~47% with regard to rate constant of the eugenol itself. A significant decrease in ROS was observed in the ND-COOH and ND-COOH/eugenol complex compared with the negative control during intracellular ROS assay. Moreover, ROS and cupric reducing antioxidant capacity evaluation showed that ND-COOH had synergistic effects of antioxidation with eugenol. Therefore, ND-COOH could be used as an excellent topical drug delivery system with improved permeability, higher stability, and minimized safety issue.

  2. Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction.

    Science.gov (United States)

    Banks, Matthew L; Hutsell, Blake A; Schwienteck, Kathryn L; Negus, S Stevens

    2015-06-01

    Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to decrease drug-maintained behaviors, but also to promote a reallocation of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940's, and during the last 10-15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser d -amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence.

  3. Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device

    Directory of Open Access Journals (Sweden)

    Jeffrey T. Borenstein

    2012-03-01

    Full Text Available The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene (PTFE membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation.

  4. Efficacy evaluation of the school program Unplugged for drug use prevention among Brazilian adolescents

    Directory of Open Access Journals (Sweden)

    Zila M. Sanchez

    2016-11-01

    Full Text Available Abstract Background Most Brazilian schools do not have a continuous program for drug use prevention and do not conduct culturally adapted activities for that purpose. This study evaluated the impact of the Unplugged program on drug use prevention among children and adolescents in public middle schools of Brazil. Methods A non-randomized controlled trial was conducted in 2013 with 2185 students in 16 public schools from 3 Brazilian cities. The intervention group attended 12 weekly classes of the Unplugged program for drug use prevention, and the control group did not attend to any school prevention programs in the same year. Multilevel analyses were used to evaluate temporal and between group changes in the consumption of each drug. Results The study suggested that there was no evidence that Unplugged effected 11- to 12-year-old students. However, the program seemed to stimulate a decrease in recent marijuana use (transition from use to non-use in 85.7% of intervention cases and 28.6% of control cases, OR = 17.5, p = 0.039 among 13- to 15-year-old students. In addition, students in this age range who received the Unplugged program had similar drug consumption levels to those observed before the program began. However, students in the control group presented a significant tendency to increase marijuana use and binge drinking. Conclusions This study adds to the evidence of program efficacy among Brazilian middle school students by presenting marginal effects on binge drinking and marijuana use. An 18-month randomized controlled trial is recommended for a future study.

  5. Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

    Directory of Open Access Journals (Sweden)

    Abeer M. El-Kady

    2015-01-01

    Full Text Available Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1 of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1 of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug.

  6. Reducing the Risk of Drug Involvement among Early Adolescents: An Evaluation of Drug Abuse Resistance Education (DARE).

    Science.gov (United States)

    Harmon, Michele Alicia

    1993-01-01

    DARE's effectiveness in Charleston County (South Carolina) was studied by comparing 341 DARE to 367 non-DARE fifth-grade students. DARE teaches students to recognize and resist social pressures to use drugs. DARE has positive impacts on anti-substance abuse attitudes, assertiveness, positive peer association, association with drug-using peers, and…

  7. Comet Assay: A Method to Evaluate Genotoxicity of Nano-Drug Delivery System

    Science.gov (United States)

    Vandghanooni, Somayeh; Eskandani, Morteza

    2011-01-01

    Introduction Drug delivery systems could induce cellular toxicity as side effect of nanomaterials. The mechanism of toxicity usually involves DNA damage. The comet assay or single cell gel electrophoresis (SCGE) is a sensitive method for detecting strand damages in the DNA of a cell with applications in genotoxicity testing and molecular epidemiology as well as fundamental research in DNA damage and repair. Methods In the current study, we reviewed recent drug delivery researches related to SCGE. Results We found that one preference for choosing the assay is that comet images may result from apoptosis-mediated nuclear fragmentation. This method has been widely used over the last decade in several different areas. Overall cells, such as cultured cells are embedded in agarose on a microscope slide, lysed with detergent, and treated with high salt. Nucleoids are supercoiled DNA form. When the slide is faced to alkaline electrophoresis any breakages present in the DNA cause the supercoiling to relax locally and loops of DNA extend toward the anode as a ‘‘comet tail’’. Conclusion This article provides a relatively comprehensive review upon potentiality of the comet assay for assessment of DNA damage and accordingly it can be used as an informative platform in genotoxicity studies of drug delivery systems. PMID:23678412

  8. Multi-site evaluation of the JULES land surface model using global and local data

    Directory of Open Access Journals (Sweden)

    D. Slevin

    2015-02-01

    Full Text Available This study evaluates the ability of the JULES land surface model (LSM to simulate photosynthesis using local and global data sets at 12 FLUXNET sites. Model parameters include site-specific (local values for each flux tower site and the default parameters used in the Hadley Centre Global Environmental Model (HadGEM climate model. Firstly, gross primary productivity (GPP estimates from driving JULES with data derived from local site measurements were compared to observations from the FLUXNET network. When using local data, the model is biased with total annual GPP underestimated by 16% across all sites compared to observations. Secondly, GPP estimates from driving JULES with data derived from global parameter and atmospheric reanalysis (on scales of 100 km or so were compared to FLUXNET observations. It was found that model performance decreases further, with total annual GPP underestimated by 30% across all sites compared to observations. When JULES was driven using local parameters and global meteorological data, it was shown that global data could be used in place of FLUXNET data with a 7% reduction in total annual simulated GPP. Thirdly, the global meteorological data sets, WFDEI and PRINCETON, were compared to local data to find that the WFDEI data set more closely matches the local meteorological measurements (FLUXNET. Finally, the JULES phenology model was tested by comparing results from simulations using the default phenology model to those forced with the remote sensing product MODIS leaf area index (LAI. Forcing the model with daily satellite LAI results in only small improvements in predicted GPP at a small number of sites, compared to using the default phenology model.

  9. Evaluation of heart rhythm variability and arrhythmia in children with systemic and localized scleroderma.

    Science.gov (United States)

    Wozniak, Jacek; Dabrowski, Rafal; Luczak, Dariusz; Kwiatkowska, Malgorzata; Musiej-Nowakowska, Elzbieta; Kowalik, Ilona; Szwed, Hanna

    2009-01-01

    To evaluate possible disturbances in autonomic regulation and cardiac arrhythmias in children with localized and systemic scleroderma. There were 40 children included in the study: 20 with systemic and 20 with localized scleroderma. The control group comprised 20 healthy children. In 24-hour Holter recording, the average rate of sinus rhythm was significantly higher in the groups with systemic and localized scleroderma than in the control group, but there was no significant difference between them. The variability of heart rhythm in both groups was significantly decreased. In the group with systemic scleroderma, single supraventricular ectopic beats were observed in 20% and runs were seen in 40% of patients. In the group with localized scleroderma, supraventricular single ectopic beats occurred in 35% of patients and runs in 45% of those studied. Ventricular arrhythmia occurred in 2 children with systemic scleroderma, but in 1 child, it was complex. The most frequent cardiac arrhythmias in both types of scleroderma in children were of supraventricular origin, whereas ventricular arrhythmias did not occur very often. There were no significant differences in autonomic disturbances manifesting as a higher heart rate and decreased heart rate variability between localized and systemic scleroderma.

  10. Breast cancer screening-opportunistic use of registry and linked screening data for local evaluation.

    Science.gov (United States)

    Roder, David; Farshid, Gelareh; Gill, Grantley; Kollias, Jim; Koczwara, Bogda; Karapetis, Chris; Adams, Jacqui; Joshi, Rohit; Keefe, Dorothy; Powell, Kate; Fusco, Kellie; Eckert, Marion; Buckley, Elizabeth; Beckmann, Kerri

    2017-06-01

    Screening has been found to reduce breast cancer mortality at a population level in Australia, but these studies did not address local settings where numbers of deaths would generally have been too low for evaluation. Clinicians, administrators, and consumer groups are also interested in local service outcomes. We therefore use more common prognostic and treatment measures and survivals to gain evidence of screening effects among patients attending 4 local hospitals for treatment. To compare prognostic, treatment, and survival measures by screening history to determine whether expected screening effects are occurring. Employing routine clinical registry and linked screening data to investigate associations of screening history with these measures, using unadjusted and adjusted analyses. Screened women had a 10-year survival from breast cancer of 92%, compared with 78% for unscreened women; and 79% of screened surgical cases had breast conserving surgery compared with 64% in unscreened women. Unadjusted analyses indicated that recently screened cases had earlier tumor node metastasis stages, smaller diameters, less nodal involvement, better tumor differentiation, more oestrogen and progesterone receptor positive lesions, more hormone therapy, and less chemotherapy. Radiotherapy tended to be more common in screening participants. More frequent use of adjunctive radiotherapy applied when breast conserving surgery was used. Results confirm the screening effects expected from the scientific literature and demonstrate the value of opportunistic use of available registry and linked screening data for indicating to local health administrations, practitioners, and consumers whether local screening services are having the effects expected. © 2016 John Wiley & Sons, Ltd.

  11. Evaluation of dynamic properties, local site effects and design ground motions: recent advances

    International Nuclear Information System (INIS)

    Sitharam, T.G.; Vipin, K.S.; James, Naveen

    2011-01-01

    Evidences from past earthquakes clearly shows that the damages due to an earthquake and its severity at a site are controlled mainly by three factors i.e., earthquake source and path characteristics, local geological and geotechnical characteristics, structural design and quality of the construction. Seismic ground response at a site is strongly influenced by local geological and soil conditions. The exact information of the geological, geomorphological and geotechnical data along with seismotectonic details are necessary to evaluate the ground response. The geometry of the subsoil structure, the soil type, the lateral discontinuities and the surface topography will also influence the site response at a particular location. In the case of a nuclear power plant, the details obtained from the site investigation will have multiple objectives: (i) for the effective design of the foundation (ii) assessment of site amplification (iii) for liquefaction potential evaluation. Since the seismic effects on the structure depend fully on the site conditions and assessment of site amplification. The first input required in evaluation of geotechnical aspect of seismic hazard is the rock level peak horizontal acceleration (PHA) values. The surface level acceleration values need to be calculated based on the site conditions and site amplification values. This paper discusses various methods for evaluating the site amplification values, dynamic soil properties, different field and laboratory tests required and various site classification schemes. In addition to these aspects, the evaluation of liquefaction potential of the site is also presented. The paper highlights on the latest testing methods to evaluate dynamic properties (shear modulus and damping ratio) of soils and techniques for estimating local site effects. (author)

  12. Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation.

    Science.gov (United States)

    Akkari, Alessandra C S; Papini, Juliana Z Boava; Garcia, Gabriella K; Franco, Margareth K K Dias; Cavalcanti, Leide P; Gasperini, Antonio; Alkschbirs, Melissa Inger; Yokaichyia, Fabiano; de Paula, Eneida; Tófoli, Giovana R; de Araujo, Daniele R

    2016-11-01

    In this study, we reported the development and the physico-chemical characterization of poloxamer 407 (PL407) and poloxamer 188 (PL188) binary systems as hydrogels for delivering ropivacaine (RVC), as drug model, and investigate their use in infiltrative local anesthesia for applications on the treatment of post-operative pain. We studied drug-micelle interaction and micellization process by light scattering and differential scanning calorimetry (DSC), the sol-gel transition and hydrogel supramolecular structure by small-angle-X-ray scattering (SAXS) and morphological evaluation by Scanning Electron Microscopy (SEM). In addition, we have presented the investigation of drug release mechanisms, in vitro/in vivo toxic and analgesic effects. Micellar dimensions evaluation showed the formation of PL407-PL188 mixed micelles and the drug incorporation, as well as the DSC studies showed increased enthalpy values for micelles formation after addition of PL 188 and RVC, indicating changes on self-assembly and the mixed micelles formation evoked by drug incorporation. SAXS studies revealed that the phase organization in hexagonal structure was not affected by RVC insertion into the hydrogels, maintaining their supramolecular structure. SEM analysis showed similar patterns after RVC addition. The RVC release followed the Higuchi model, modulated by the PL final concentration and the insertion of PL 188 into the system. Furthermore, the association PL407-PL188 induced lower in vitro cytotoxic effects, increased the duration of analgesia, in a single-dose model study, without evoking in vivo inflammation signs after local injection. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Comparative evaluation of local poultry breeds status in Algeria, Vietnam and the Democratic Republic of Congo

    OpenAIRE

    Moula, Nassim; Farnir, Frédéric; Abdellah, Salhi; Do Duc, Luc; Vu Dinh, Ton; Leroy, Pascal; Antoine-Moussiaux, Nicolas

    2012-01-01

    Local chicken breeds contribute significantly to the world production of meat and eggs. Indigenous breeds represent 80% of the world poultry population. However, the majority of these breeds has not been recorded and studied. About 40% of poultry breeds have an unknown risk status. Hence, considerable efforts are necessary to evaluate them. Obviously, managing animal genetic resources requires the identification of the concerned phenotypes, population sizes, their geographical ...

  14. Evaluation of the functionality of biodegradable polymeric platforms for drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Gioti, M., E-mail: mgiot@physics.auth.gr; Karagkiozaki, V.; Basgiouraki, A.; Karagiannidis, P.G.; Logothetidis, S.

    2013-09-15

    We present the development of a drug-loaded triple-layer platform consisting of thin film biodegradable polymers, in a properly designed form for the desired gradual degradation. Poly(DL-lactide-co-glycolide) (PLGA (65:35), PLGA (75:25)) and polycaprolactone (PCL) were grown by spin coating technique, to synthesize the platforms with the order PCL/PLGA (75:25)/PLGA (65:35) that determine their degradation rates. The outer PLGA (65:35) layer was loaded with dipyridamole, an antiplatelet drug. Spectroscopic ellipsometry (SE) in the Vis-far UV range was used to determine the nanostructure, as well as the content of the incorporated drug in the as-grown platforms. In situ and real-time SE measurements were carried out using a liquid cell for the dynamic evaluation of the fibrinogen and albumin protein adsorption processes. Atomic force microscopy studies justified the SE results concerning the nanopores formation in the polymeric platforms, and the dominant adsorption mechanisms of the proteins, which were defined by the drug incorporation in the platforms.

  15. In vitro evaluation of paclitaxel loaded amorphous chitin nanoparticles for colon cancer drug delivery.

    Science.gov (United States)

    Smitha, K T; Anitha, A; Furuike, T; Tamura, H; Nair, Shantikumar V; Jayakumar, R

    2013-04-01

    Chitin and its derivatives have been widely used in drug delivery applications due to its biocompatible, biodegradable and non-toxic nature. In this study, we have developed amorphous chitin nanoparticles (150±50 nm) and evaluated its potential as a drug delivery system. Paclitaxel (PTX), a major chemotherapeutic agent was loaded into amorphous chitin nanoparticles (AC NPs) through ionic cross-linking reaction using TPP. The prepared PTX loaded AC NPs had an average diameter of 200±50 nm. Physico-chemical characterization of the prepared nanoparticles was carried out. These nanoparticles were proven to be hemocompatible and in vitro drug release studies showed a sustained release of PTX. Cellular internalization of the NPs was confirmed by fluorescent microscopy as well as by flow cytometry. Anticancer activity studies proved the toxicity of PTX-AC NPs toward colon cancer cells. These preliminary results indicate the potential of PTX-AC NPs in colon cancer drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Hanna M Vesterinen

    Full Text Available To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil as lead candidates for clinical evaluation.We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

  17. Self-microemulsifying drug delivery system for improved oral bioavailability of dipyridamole: preparation and evaluation.

    Science.gov (United States)

    Guo, Feng; Zhong, Haijun; He, Jing; Xie, Baogang; Liu, Fen; Xu, Helin; Liu, Minmin; Xu, Chunlian

    2011-07-01

    Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying drug delivery system (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile WL 1349, 42% Solutol HS 15 and 28% isopropyl alcohol. It was found that the performance of self-microemulsification with the combination of oleic acid and Labrafac lipophile WL 1349 increased compared with just one oil. The results obtained from an in vitro dissolution assay indicated that dipyridamole in SMEDDS dissolved rapidly and completely in pH 6.8 aqueous media, while the commercial drug tablet was less soluble. An oral bioavailability study in rats showed that dipyridamole in the SMEDDS formulation had a 2.06-fold increased absorption compared with the simple drug suspension. It was evident that SMEDDS may be an effective approach to improve the oral absorption for drugs having pH-dependent solubility.

  18. Evaluation of a needle social marketing strategy to control HIV among injecting drug users in China.

    Science.gov (United States)

    Wu, Zunyou; Luo, Wei; Sullivan, Sheena G; Rou, Keming; Lin, Peng; Liu, Wei; Ming, Zhongqiang

    2007-12-01

    To evaluate the effectiveness of a needle social marketing strategy to reduce needle sharing and hepatitis C Virus (HCV)/HIV transmission among injecting drug users (IDU) in China. Two-armed, prospective, community-randomized prevention trial. Four counties/townships in Guangxi and Guangdong provinces; one randomized to intervention the other to control in each province. Injecting drug users: 823 (443 intervention, 382 control) at baseline and 852 (415 intervention, 407 control) at the second cross-sectional survey 12 months later. A needle social marketing programme, including promotion of safe injection norms and increased access to clean needles over a 12 month period. Cross sectional surveys at baseline and follow-up compared changes in drug using behaviours and HIV and HCV rates in the intervention and control communities. Needle sharing behaviours were similar in the two groups at baseline (68.4 vs. 67.8%), and dropped significantly to 35.3% in the intervention community and remained relatively stable in the control community (62.3%; P marketing can reduce risky injecting behaviour and HIV/HCV transmission among injecting drug users in China and should be expanded.

  19. Association of localized hypersensitivity and in-stent neoatherosclerosis with the very late drug-eluting stent thrombosis.

    Directory of Open Access Journals (Sweden)

    Kyohei Yamaji

    Full Text Available Localized hypersensitivity reaction, delayed arterial healing, and neoatherosclerosis inside the stent have been suggested as the underlying pathologic mechanisms of very late stent thrombosis (VLST of drug-eluting stent (DES. The present study sought to explore the prevalence of inflammatory cell infiltrates and evidence for fragments of atherosclerotic plaques in the aspirated thrombi in patients with DES VLST.From April 2004 to September 2012, 48 patients with stent thrombosis (ST of DES underwent thrombus aspiration with retrieved material sufficient for the histopathologic analysis; early ST (EST, within 30 days: N = 17, late ST (LST, between 31 and 365 days: N = 7, and very late ST (VLST, >1 year: N = 24. Eosinophil fraction in the aspirated thrombi was significantly higher in patients with VLST (8.2±5.7% as compared with those with EST (4.3±3.0% and LST (5.5±3.8% (P = 0.03. Eosinophil fraction in the aspirated thrombi was significantly higher in 12 VLST patients with angiographic peri-stent contrast staining (PSS and/or incomplete stent apposition (ISA by intravascular ultrasound than in 12 VLST patients without PSS or ISA (10.6±6.1% versus 5.8±4.1%, P = 0.03. Evidences for fragments of atherosclerotic plaques in the aspirated thrombi were observed only in 3 (13% out of 24 patients with DES VLST.Eosinophil fraction in the aspirated thrombi was significantly higher in patients with DES VLST as compared with those with EST and LST. Evidences for fragments of atherosclerotic plaques were relatively uncommon in patients with DES VLST.

  20. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

    Science.gov (United States)

    Patel, Meghavi

    Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core

  1. Carboxytherapy for treatment of localized chronic plaque psoriasis: Clinical and histopathologic evaluation.

    Science.gov (United States)

    Kamel, Abeer Mostafa; Abdelghani, Rania

    2018-01-17

    Multiple treatment options are introduced in treatment of chronic localized plaque psoriasis but with poor adherence and poor patients' satisfaction resulting in poor treatment outcome. In this pilot study, we investigated the safety and efficacy of carboxytherapy in treatment of chronic localized plaque psoriasis. Thirty adult patients with chronic localized plaque psoriasis were enrolled in this study. The patients received carboxytherapy injection once/week for 8 weeks. Patients were clinically and histpathologically evaluated 2 weeks after the last treatment. Clinical response was evaluated by investigator's global assessment, total sign score, and 5-point scale for perilesional erythema. We performed 10-point visual analog scale for patient's satisfaction, and side effects. Three months after the last session we evaluate recurrence using 10-point scale. Carboxytherapy achieved treatment success in 26.6% according to investigator's global assessment and total sign score and 70% of the patients demonstrated absence of perilesional erythema. Patients were satisfied with no reported side effects. Recurrence area was within 1% -10% of the baseline area in 83.3% of the improved patients. © 2018 Wiley Periodicals, Inc.

  2. Vertebral hemangioma: an important differential in the evaluation of locally aggressive spinal lesions.

    Science.gov (United States)

    Alexander, Justin; Meir, Adam; Vrodos, Nikitas; Yau, Yun-Hom

    2010-08-15

    A case report and a discussion of recent published data. To highlight the importance of vertebral hemangioma (VH) as a differential diagnosis in the evaluation of locally aggressive spinal lesions. VH commonly occur as incidental findings, however, locally aggressive VH have been described. Difficulties in diagnosing these lesions are well reported and relate to changes in fat content causing uncharacteristic appearances on imaging. The management options for these lesions include a combination of observation, embolization, sclerotherapy, surgical decompression, or stabilization and radiotherapy. A 45-year-old patient who was previously well presented with back pain and rapidly progressive paraparesis. Imaging confirmed the presence of an extensive lesion centered within the right T3 vertebral pedicle with intrusion into the spinal canal. Urgent surgical decompression was undertaken and was complicated by extensive intraoperative hemorrhage requiring massive transfusion. Histologically, the lesion was shown to be a cavernous VH with no evidence of malignancy. Following radiation oncology review, he was offered adjuvant radiotherapy to minimize the risks of recurrence. He achieved a near full neurologic recovery within 2 weeks and had a full recovery by 12 months. VH should be considered in the evaluation of locally aggressive spinal lesions. Angiography is a useful adjunct in the evaluation of these lesions, both as a diagnostic and therapeutic tool. After diagnosed correctly a wide range of treatment options exist that may prevent the patient from undergoing major surgical resection and reconstruction procedures, which may be associated with high rates of morbidity.

  3. Evaluating the engagement of universities in capacity building for sustainable development in local communities.

    Science.gov (United States)

    Shiel, Chris; Leal Filho, Walter; do Paço, Arminda; Brandli, Luciana

    2016-02-01

    Universities have the potential to play a leading role in enabling communities to develop more sustainable ways of living and working however, sustainable communities may only emerge with facilitation, community learning and continual efforts to build their capacities. Elements of programme planning and evaluation on the one hand, and capacity building on the other, are needed. The latter entails approaches and processes that may contribute to community empowerment; universities may either lead such approaches, or be key partners in an endeavour to empower communities to address the challenges posed by the need for sustainable development. Although capacity building and the promotion of sustainable development locally, are on the agenda for universities who take seriously regional engagement, very little is published that illustrates or describes the various forms of activities that take place. Further, there is a paucity of studies that have evaluated the work performed by universities in building capacity for sustainable development at the local level. This paper is an attempt to address this need, and entails an empirical study based on a sample of universities in the United Kingdom, Germany, Portugal and Brazil. The paper examines the extent to which capacity building for sustainable development is being undertaken, suggests the forms that this might take and evaluates some of the benefits for local communities. The paper concludes by reinforcing that universities have a critical role to play in community development; that role has to prioritise the sustainability agenda. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Evaluation of local power distribution with fine-mesh core model for the HTTR

    International Nuclear Information System (INIS)

    Murata, Isao; Yamashita, Kiyonobu; Maruyama, So; Shindo, Ryuichi; Fujimoto, Nozomu; Sudo, Yukio; Nakata, Tetsuo.

    1991-01-01

    An evaluation method of the local power distribution was developed considering the radial and axial heterogeneity caused by fuel rods, BP rods and block end graphite for the High Temperature Engineering Test Reactor (HTTR) in Japan Atomic Energy Research Institute (JAERI). The evaluation method was verified through the analyses of critical assembly experiments. A good agreement was obtained between calculations and measurements and the difference was less than 3 % on the power distribution. This method was applied to the core design for the HTTR to evaluate the maximum fuel temperature. From these results, it was confirmed that this evaluation method has an enough accuracy and is able to predict the detailed power distribution of the HTTR. (author)

  5. Development of engineering program for integrity evaluation of pipes with local wall thinned defects

    International Nuclear Information System (INIS)

    Park, Chi Yong; Lee, Sung Ho; Kim, Tae Ryong; Park, Sang Kyu

    2008-01-01

    Integrity evaluation of pipes with local wall thinning by erosion and corrosion is increasingly important in maintenance of wall thinned carbon steel pipes in nuclear power plants. Though a few program for integrity assessment of wall thinned pipes have been developed in domestic nuclear field, however those are limited to straight pipes and methodology proposed in ASME Sec.XI Code Case N-597. Recently, the engineering program for integrity evaluation of pipes with all kinds of local wall defects such as straight, elbow, reducer and branch pipes was developed successfully. The program was designated as PiTEP (Pipe Thinning Evaluation Program), which name was registered as a trademark in the Korea Intellectual Property Office. A developed program is carried out by sequential step of four integrity evaluation methodologies, which are composed of construction code, code case N-597, its engineering method and two developed owner evaluation method. As PiTEP program will be performed through GUI (Graphic User Interface) with user's familiarity, it would be conveniently used by plant engineers with only measured thickness data, basic operation conditions and pipe data

  6. Comparative evaluation of the drug interaction screening programs MediQ and ID PHARMA CHECK in neurological inpatients.

    Science.gov (United States)

    Zorina, Olesya I; Haueis, Patrick; Semmler, Alexander; Marti, Isabelle; Gonzenbach, Roman R; Guzek, Markus; Kullak-Ublick, Gerd A; Weller, Michael; Russmann, Stefan

    2012-08-01

    The comparative evaluation of clinical decision support software (CDSS) programs regarding their sensitivity and positive predictive value for the identification of clinically relevant drug interactions. In this research, we used a cross-sectional study that identified potential drug interactions using the CDSS MediQ and the ID PHARMA CHECK in 484 neurological inpatients. Interactions were reclassified according to the Zurich Interaction System, a multidimensional classification that incorporates the Operational Classification of Drug Interactions. In 484 patients with 2812 prescriptions, MediQ and ID PHARMA CHECK generated a total of 1759 and 1082 alerts, respectively. MediQ identified 658 unique potentially interacting combinations, 8 classified as "high danger," 164 as "average danger," and 486 as "low danger." ID PHARMA CHECK detected 336 combinations assigned to one or several of 12 risk and management categories. Altogether, both CDSS issued alerts relating to 808 unique potentially interacting combinations. According to the Zurich Interaction System, 6 of these were contraindicated, 25 were provisionally contraindicated, 190 carried a conditional risk, and 587 had a minimal risk of adverse events. The positive predictive value for alerts having at least a conditional risk was 0.24 for MediQ and 0.48 for ID PHARMA CHECK. CDSS showed major differences in the identification and grading of interactions, and many interactions were only identified by one of the two CDSS. For both programs, only a small proportion of all identified interactions appeared clinically relevant, and the selected display of alerts that imply management changes is a key issue in the further development and local setup of such programs. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Evaluation of Patients Hospitalized in Intensive Care Unit Due to Drug-Related Suicide Attempt and Access to Drugs: A Single Center Prospective Study

    Directory of Open Access Journals (Sweden)

    Fatih Doğu Geyik

    2014-06-01

    Full Text Available Aim: We aimed to evaluate patients who were hospitalized in our intensive care unit due to drug-related suicide attempt (medical or insecticides and their access to these drugs. Methods: We prospectively recorded the demographic characteristics and medical data of 50 patients (32 females and 18 males who were hospitalized in our intensive care unit due to drug-related suicide attempt. Results: 66% of subjects were between the ages of 15 and 24 years with a mean age of 25.4±8.8 years. Multiple drug overdose was observed in 28% of patients. The unemployment rate was higher for women than men (p<0.001. Men obtained drugs from pharmacy more often than women (27.8% vs 6.2%, p=0,03. Of the patients, 86% got the drugs from home medicine cabinet while this rate was 93% among women (n=30. The level of toxicity was higher among patients who got the drugs from pharmacy than in those who used drugs at home (p=0.06. The length of stay in the intensive care unit was longer among patients with toxic level of medication (p=0.001. Conclusion: Patients usually use drugs or insecticides available at home to commit suicide. We believe that in patients with risk of suicide attempt, access to drugs should be limited and state regulations should be applied. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52:111-5

  8. Comparative evaluation of polymersome versus micelle structures as vehicles for the controlled release of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Alibolandi, Mona [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of); Ramezani, Mohammad; Abnous, Khalil [Mashhad University of Medical Sciences, Pharmaceutical Research Center, School of Pharmacy (Iran, Islamic Republic of); Sadeghi, Fatemeh, E-mail: sadeghif@mums.ac.ir [Mashhad University of Medical Sciences, Targeted Drug Delivery Research Center, School of Pharmacy (Iran, Islamic Republic of); Hadizadeh, Farzin, E-mail: hadizadehf@mums.ac.ir [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of)

    2015-02-15

    Di-block copolymers composed of two biocompatible polymers, poly(ethylene glycol) and poly(d,l-lactide), were synthesized by ring-opening polymerization for the preparation of doxorubicin-loaded self-assembled nanostructures, including polymeric vesicles (polymersomes) and micelles. The capability and stability of the nanostructures prepared for the controlled release of DOX are discussed in this paper. The in vitro drug release at 37 °C was evaluated up to 6 days at pH 7.4 and 5.5 and in the presence of 50 % FBS. The cellular uptake and cytotoxicity effect of both formulations were also evaluated in the MCF-7 cell line. The SEM and AFM images confirmed the hollow spherical structure of the polymersomes and the solid round structures of the micelles. The TEM results also revealed the uniformity in size and shape of the drug-loaded micelle and polymersome nanostructures. The DOX-loaded micelles and polymersomes presented efficient anticancer performance, as verified by flow cytometry and MTT assay tests. The most important finding of this study is that the prepared nanopolymersomes presented significant increases in the doxorubicin encapsulation efficiency and the stability of the formulation in comparison with the micelle formulation. In vitro studies revealed that polymersomes may be stable in the blood circulation and meet the requirements for an effective drug delivery system.

  9. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kejian, E-mail: kejian.wang.bio@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

  10. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

    International Nuclear Information System (INIS)

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-01-01

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development

  11. MARKETING STUDIES OF LOCAL MARKET OF DRUGS WHICH ARE APPLIED FOR PREVENTION AND TREATMENT OF ORAL CAVITY DISEASES

    Directory of Open Access Journals (Sweden)

    O. A. Tsarakhov

    2015-01-01

    Full Text Available Stomatological market has actively developed recent years. Domestic experts received an access to contemporary technologies of dental diseases treatment in the world. This conditioned the appearance of new drugs and parapharmaceutical products applied in dental practice on the pharmaceutical market. In this connection, study of these drugs market, their price policy, demand and supply. Assortment of parapharmaceutical products applied in dental practice for oral cavity hygiene is represented mainly by liquid forms, such as mouth rinse, balms, elixirs, and a special place is occupied by toothpastes. Their assortment amounts to more than 700 types. Drugs, applied in dental practice are represented by the following groups: anti-inflammatory, antimicrobial, antiallergenic, anesthetics, drugs which stimulate tissues regeneration, fluoric drugs. The purpose of this study was the analysis of regional pharmaceutical market assortment, which offers parapharmaceutical goods and drugs for prevention and treatment of oral cavity diseases to the stomatological establishments. Pharmaceutical market of the Republic of North Ossetia – Alania is represented by a wide range of drugs for dental diseases treatment. This group is represented in the assortment of practically all distributors. The drugs for dental diseases treatment is not only supplied by domestic producers but also go from pharmaceutical companies of 29 foreign countries, which influences positively on the state of drug therapy of paradontum in the region.

  12. AVIDITY EVALUATION OF LOCAL IgA ANTIBODIES IN PERSONS IMMUNIZED WITH LIVE INFLUENZA VACCINE

    Directory of Open Access Journals (Sweden)

    S. A. Donina

    2008-01-01

    Full Text Available Abstract. At present, immunogenicity evaluation of influenza vaccines is performed by quantitative assessment of increased serum antibodies. It was, however, shown that the degree of human defense against influenza is mostly related to their qualitative characteristics, i.e., avidity (functional activity. Leading role of local immunity is demonstrated in protection against influenza. Such immunity is mediated by IgA antibodies from mucosal airways. Meanwhile, the avidity issues for local antibodies still remain open.In present study, an attempt was undertaken to evaluate post-vaccination local immunological memory for influenza A virus, according to IgA antibodies from upper respiratory secretions. Two techniques were used to evaluate antibody avidity, that were previously applied for studying this phenomenon with serum imunoglobulins, i.e., a dynamic test (measurement of antigen-antibody reaction rates, and a test with urea, a chaotropic agent (avidity is determined as a strength of antigen-antibody complex. A total of 202 persons (18 to 20 years old were enrolled into the study.With both tests, a broad range of individual avidity values was observed for the antibodies. A significant cohort (up to 30 per cent of persons immunized with live influenza vaccine, showed sharply increased avidity of secretory IgA antibodies by both methods, along with accumulation of these immunoglobulins after vaccination. A reverse relationship is revealed between avidity levels of these antibodies before vaccination, and increase of this parameter post-immunization. The data present convincing arguments for specific renewal of local humoral immunological memory, as induced by live influenza vaccine. The study substantiates a necessity for application of the both tests in parallel, when determining avidity of secretory IgA antibodies. (Med. Immunol., vol. 10, N 4-5, pp 423-430.

  13. Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

    Science.gov (United States)

    Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

    2016-04-01

    Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

  14. Evaluation of China's local enforcement of energy efficiency standards and labeling programs for appliances and equipment

    International Nuclear Information System (INIS)

    Khanna, Nina Zheng; Zhou, Nan; Fridley, David; Fino-Chen, Cecilia

    2013-01-01

    Aims: This paper aims to evaluate local enforcement of China's mandatory appliance and equipment energy efficiency standards and labeling programs, two increasingly important policies for meeting national energy and carbon reduction targets. The expected energy savings of efficiency standards and labels can be fully realized only with strong enforcement to ensure compliance for all products sold. This paper provides comprehensive retrospective evaluation of the methodologies, results, progress and remaining challenges in pilot enforcement projects initiated in the absence of consistent national check-testing focused on energy efficiency. Scope: This paper's scope is focused on 2006–2009 pilot local check-tests conducted to verify appliance and equipment compliance with China's mandatory energy label and efficiency standards. Conclusions: This paper finds both improvement and some backsliding in compliance rates over time. Compared to earlier efforts, 2009 check-tests covered a wider regional and product scope but demonstrated greater variation in compliance rates. Labeling display and energy efficiency compliance was generally high across regions and most products, but lower compliance rates were observed in less economically developed regions and for lighting and industrial products. Based on these findings, areas for improvement in local awareness, product sampling methodology, check-testing tools and procedures are identified. - Highlights: • China's mandatory standards and labeling crucial to national energy saving goals. • China's 2006–2009 pilot efficiency check-testing for standards and labeling evaluated. • Wider geographic and product scope in 2009, but greater variation in compliance. • Generally high compliance, but lower rates for less economically developed region. • Local check-test capacity improving but methodological challenges remain

  15. Evaluation and appraisal of drug information services in a rural secondary level care hospital, Anantapur, AP

    Directory of Open Access Journals (Sweden)

    Rohit Bhavsar

    2012-01-01

    Full Text Available Background: Drug Information Center (DIC is an information center which provides drug information (DI to healthcare professionals. The aim was to evaluate the performance of DIC for improving the quality and quantity of information services provided to the healthcare professionals. The service was provided free of cost to the customers. Materials and Methods: This descriptive study was conducted for the period of 6 months from February to August 2011 excluding May due to vacation. Customers were asked: how did they find the service provided to them? Was it good, satisfactory, or need improvement? There were written feedback forms to be filled by the customers, including customer satisfaction questions. The official publication of the DIC, RIPER PDIC Bulletin was screened for its types of articles/number of drug news published. The bulletin is circulated for free to the healthcare professionals electronically. Results and Discussion: A total of 232 queries were obtained during the study period of 6 months. Average number of queried received to the DIC was 39 per month. Most preferred mode of queries was personal access (89%. Majority of queries were received from nurses, i.e., 162 (70% queries and 81% of all queries were drug oriented for improving knowledge. There were only 19% of the queries for individual patients; doctors asked most of those queries. Only 3% queries answered were rated as need improvement by the healthcare professionals. Rest were considered as either Good (56% or satisfactory (49%. Range of drug news published in each bulletin was 3-4 and most of the other articles include expert opinion to improve practice or training. Conclusion: The DI services were satisfactorily used for academic interests. Nurses used the service for the highest compared to other health care professionals. Future studies should plan to establish the usefulness of DI to improve healthcare practice.

  16. The American Medicine Chest Challenge: Evaluation of a Drug Take-Back and Disposal Campaign.

    Science.gov (United States)

    Yanovitzky, Itzhak

    2016-07-01

    Prescription drug take-back programs provide a safe and convenient way to dispose of expired, unwanted, or unused medications that people store in homes, thus limiting the potential misuse of prescription drugs. This study evaluated public response to a social marketing campaign promoting a community-based drug take-back program, the American Medicine Chest Challenge. A telephone survey was conducted with a representative sample of adults in New Jersey (N = 906) 2 weeks following the conclusion of the statewide collection day event in November 2010. The survey assessed public exposure to the campaign and the extent to which it is associated with public perceptions and behaviors the campaign was designed to influence. The campaign, which relied heavily on community channels for the dissemination of messages, was able to reach directly more than 60% of its target audience. When potential confounders were controlled for, campaign exposure was a strong predictor of a respondent having one or more conversations with others about medicine disposal (odds ratio [OR] = 2.4, 95% CI [1.5, 3.6]); actually disposing of expired, unwanted, or unused medicine in a collection site (OR = 2.14, 95% CI [1.15, 3.9]); and talking to kids about the dangers of prescription drug abuse (OR = 1.65, 95% CI [1.1, 2.45])-all of which were exclusively promoted through the campaign. This case illustrates the potential efficacy of community-based prevention marketing efforts to stimulate community discourse regarding the dangers of prescription drug misuse and to decrease the availability of expired, unwanted, or unused medicine in the community.

  17. Evaluation of anti-GERD activity of gastro retentive drug delivery system of itopride hydrochloride.

    Science.gov (United States)

    Satapathy, Trilochan; Panda, Prasana K; Goyal, Amit K; Rath, Goutam

    2010-08-01

    The present work describes the formulation and evaluation of the gastroretentive system of Itopride hydrochloride. In this research, we have formulated floating hydrogel-based microspheres employing calcium carbonate (CaCO(3)) as a gas forming agent dispersed in alginate matrix. In vitro characterizations such as drug content, particle size, and drug release were carried out. GI motility was determined by administration of charcoal meal to rats. Results demonstrated that prepared microspheres were spherical in shape with smooth surface, good loading efficiency, and excellent buoyancy. The gastro retentive dosage form of itiopride demonstrated significant antacid, anti-ulcer, and anti-GERD activity after 12 hours in comparison with the conventional dosage form.

  18. Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.

    Science.gov (United States)

    Carmona-Moran, Carlos A; Zavgorodnya, Oleksandra; Penman, Andrew D; Kharlampieva, Eugenia; Bridges, S Louis; Hergenrother, Robert W; Singh, Jasvinder A; Wick, Timothy M

    2016-07-25

    Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, ptransdermal drug formulations with adjustable drug transport kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. DRUG COURTS: Better DOJ Data Collection and Evaluation Efforts Needed to Measure Impact of Drug Court Programs

    National Research Council Canada - National Science Library

    2002-01-01

    .... Under this concept, in exchange for the possibility of dismissed charges or reduced sentences, defendants are diverted to drug court programs in various ways and at various stages in the judicial process...

  20. A Reliable Method for the Evaluation of the Anaphylactoid Reaction Caused by Injectable Drugs

    Directory of Open Access Journals (Sweden)

    Fang Wang

    2016-10-01

    Full Text Available Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat and different modes of administration (intramuscular, intravenous and intraperitoneal injection and different times (15 min, 30 min and 60 min were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which

  1. Novel approaches to improve iris recognition system performance based on local quality evaluation and feature fusion.

    Science.gov (United States)

    Chen, Ying; Liu, Yuanning; Zhu, Xiaodong; Chen, Huiling; He, Fei; Pang, Yutong

    2014-01-01

    For building a new iris template, this paper proposes a strategy to fuse different portions of iris based on machine learning method to evaluate local quality of iris. There are three novelties compared to previous work. Firstly, the normalized segmented iris is divided into multitracks and then each track is estimated individually to analyze the recognition accuracy rate (RAR). Secondly, six local quality evaluation parameters are adopted to analyze texture information of each track. Besides, particle swarm optimization (PSO) is employed to get the weights of these evaluation parameters and corresponding weighted coefficients of different tracks. Finally, all tracks' information is fused according to the weights of different tracks. The experimental results based on subsets of three public and one private iris image databases demonstrate three contributions of this paper. (1) Our experimental results prove that partial iris image cannot completely replace the entire iris image for iris recognition system in several ways. (2) The proposed quality evaluation algorithm is a self-adaptive algorithm, and it can automatically optimize the parameters according to iris image samples' own characteristics. (3) Our feature information fusion strategy can effectively improve the performance of iris recognition system.

  2. Evaluation of a cloud-based local-read paradigm for imaging evaluations in oncology clinical trials for lung cancer

    International Nuclear Information System (INIS)

    Sueoka-Aragane, Naoko; Kobayashi, Naomi; Bonnard, Eric; Charbonnier, Colette; Yamamichi, Junta; Mizobe, Hideaki; Kimura, Shinya

    2015-01-01

    Although tumor response evaluated with radiological imaging is frequently used as a primary endpoint in clinical trials, it is difficult to obtain precise results because of inter- and intra-observer differences. To evaluate usefulness of a cloud-based local-read paradigm implementing software solutions that standardize imaging evaluations among international investigator sites for clinical trials of lung cancer. Two studies were performed: KUMO I and KUMO I Extension. KUMO I was a pilot study aiming at demonstrating the feasibility of cloud implementation and identifying issues regarding variability of evaluations among sites. Chest CT scans at three time-points from baseline to progression, from 10 patients with lung cancer who were treated with EGFR tyrosine kinase inhibitors, were evaluated independently by two oncologists (Japan) and one radiologist (France), through a cloud-based software solution. The KUMO I Extension was performed based on the results of KUMO I. KUMO I showed discordance rates of 40% for target lesion selection, 70% for overall response at the first time-point, and 60% for overall response at the second time-point. Since the main reason for the discordance was differences in the selection of target lesions, KUMO I Extension added a cloud-based quality control service to achieve a consensus on the selection of target lesions, resulting in an improved rate of agreement of response evaluations. The study shows the feasibility of imaging evaluations at investigator sites, based on cloud services for clinical studies involving multiple international sites. This system offers a step forward in standardizing evaluations of images among widely dispersed sites

  3. Comprehensive evaluation of carboxylated nanodiamond as a topical drug delivery system

    Directory of Open Access Journals (Sweden)

    Lim DG

    2016-05-01

    Full Text Available Dae Gon Lim,1,* Ki Hyun Kim,1,* Eunah Kang,2 Sun Hee Lim,3 Jeremy Ricci,3 Si Kwon Sung,3 Myoung Taek Kwon,3 Seong Hoon Jeong1 1College of Pharmacy, Dongguk University-Seoul, Gyeonggi, 2School of Chemical Engineering and Material Science, Chung-Ang University, 3NanoResource Co. Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Abstract: The best strategy in the development of topical drug delivery systems may be to facilitate the permeation of drugs without any harmful effects, while staying on the skin surface and maintaining stability of the system. Nanodiamonds (NDs play a key role with their excellent physicochemical properties, including high biocompatibility, physical adsorption, reactive oxygen species (ROS scavenging capability, and photostabilizing activity. Z-average sizes of carboxylated ND (ND–COOH agglutinate decreased significantly as the pH increased. Fluorescein-conjugated ND was observed only on the stratum corneum, and no sample diffused into the dermal layer even after 48 hours. Moreover, ND–COOH and ND–COOH/eugenol complex did not show significant toxic effects on murine macrophage cells. ND improved in vitro skin permeation >50% acting as a “drug reservoir” to maintain a high drug concentration in the donor chamber, which was supported by quartz crystal microbalance results. Moreover, ND–COOH could adsorb a drug amount equivalent to 80% of its own weight. A photostability study showed that ND–COOH increased the photostability ~47% with regard to rate constant of the eugenol itself. A significant decrease in ROS was observed in the ND–COOH and ND–COOH/eugenol complex compared with the negative control during intracellular ROS assay. Moreover, ROS and cupric reducing antioxidant capacity evaluation showed that ND–COOH had synergistic effects of antioxidation with eugenol. Therefore, ND–COOH could be used as an excellent topical drug delivery system with improved permeability

  4. Monitoring and evaluation of disaster response efforts undertaken by local health departments: a rapid realist review.

    Science.gov (United States)

    Gossip, Kate; Gouda, Hebe; Lee, Yong Yi; Firth, Sonja; Bermejo, Raoul; Zeck, Willibald; Jimenez Soto, Eliana

    2017-06-29

    Local health departments are often at the forefront of a disaster response, attending to the immediate trauma inflicted by the disaster and also the long term health consequences. As the frequency and severity of disasters are projected to rise, monitoring and evaluation (M&E) efforts are critical to help local health departments consolidate past experiences and improve future response efforts. Local health departments often conduct M&E work post disaster, however, many of these efforts fail to improve response procedures. We undertook a rapid realist review (RRR) to examine why M&E efforts undertaken by local health departments do not always result in improved disaster response efforts. We aimed to complement existing frameworks by focusing on the most basic and pragmatic steps of a M&E cycle targeted towards continuous system improvements. For these purposes, we developed a theoretical framework that draws on the quality improvement literature to 'frame' the steps in the M&E cycle. This framework encompassed a M&E cycle involving three stages (i.e., document and assess, disseminate and implement) that must be sequentially completed to learn from past experiences and improve future disaster response efforts. We used this framework to guide our examination of the literature and to identify any context-mechanism-outcome (CMO) configurations which describe how M&E may be constrained or enabled at each stage of the M&E cycle. This RRR found a number of explanatory CMO configurations that provide valuable insights into some of the considerations that should be made when using M&E to improve future disaster response efforts. Firstly, to support the accurate documentation and assessment of a disaster response, local health departments should consider how they can: establish a culture of learning within health departments; use embedded training methods; or facilitate external partnerships. Secondly, to enhance the widespread dissemination of lessons learned and facilitate

  5. [Indicators of statin use as a model for qualitative evaluation of chronic disease management in the Local Health Unit Roma B].

    Science.gov (United States)

    Ciaralli, Fabrizio; Summaria, Francesco; Mustilli, Marina; Vasselli, Loredana; D'Urso, Antonio; Degrassi, Flori

    2010-01-01

    In chronic diseases the adherence and persistence to therapeutic treatments are often lower than guidelines said. This leads to a worse therapeutic effect of the treatments and to a misuse in healthcare costs. Our study evaluates the impact of a pharmacoutilization analysis model, derived from the administrative database of the Local Health Unit Roma B. In particularly we calculate some indicators of adherence, persistence, occasional treatment and switch in patients on statins secondary prevention treatment (patients discharged from Hospital with Acute Myocardial Infarction diagnosis). The model that we developed would be successfully used in the cost-effective analysis of other drugs.

  6. Evaluating Local Primary Dendrite Arm Spacing Characterization Techniques Using Synthetic Directionally Solidified Dendritic Microstructures

    Science.gov (United States)

    Tschopp, Mark A.; Miller, Jonathan D.; Oppedal, Andrew L.; Solanki, Kiran N.

    2015-10-01

    Microstructure characterization continues to play an important bridge to understanding why particular processing routes or parameters affect the properties of materials. This statement certainly holds true in the case of directionally solidified dendritic microstructures, where characterizing the primary dendrite arm spacing is vital to developing the process-structure-property relationships that can lead to the design and optimization of processing routes for defined properties. In this work, four series of simulations were used to examine the capability of a few Voronoi-based techniques to capture local microstructure statistics (primary dendrite arm spacing and coordination number) in controlled (synthetically generated) microstructures. These simulations used both cubic and hexagonal microstructures with varying degrees of disorder (noise) to study the effects of length scale, base microstructure, microstructure variability, and technique parameters on the local PDAS distribution, local coordination number distribution, bulk PDAS, and bulk coordination number. The Voronoi tesselation technique with a polygon-side-length criterion correctly characterized the known synthetic microstructures. By systematically studying the different techniques for quantifying local primary dendrite arm spacings, we have evaluated their capability to capture this important microstructure feature in different dendritic microstructures, which can be an important step for experimentally correlating with both processing and properties in single crystal nickel-based superalloys.

  7. A study on regional comprehensive performance evaluation indicator system of rational use of drugs

    Directory of Open Access Journals (Sweden)

    Sun Tongda

    2017-01-01

    Full Text Available The current research presents the design of a 4-degree-3-level performance evaluation indicator system of rational use of drugs for health care institutions accord with the Balanced Score Card (BSC method. Financial index, patient index, professional process index, and development and blazing new trials index are adopted in the light of scientific, guiding, operable and generalizable principles. The index weight is based on the analytic hierarchy process, and comprehensive performance evaluation indicators are calculated by a linear integrated weighting method. Its practical application in 21 state-run health care institutions in Ningbo, from 2008 to 2012, has arrived at the finding that the comprehensive performance evaluation indicator system offers a scientific, practical and effective performance management quantification and is thus worth popularizing.

  8. Localization of Broca's Area Using Functional MR Imaging: Quantitative Evaluation of Paradigms.

    Science.gov (United States)

    Kim, Chi Heon; Kim, Jae-Hun; Chung, Chun Kee; Kim, June Sic; Lee, Jong-Min; Lee, Sang Kun

    2009-04-01

    Functional magnetic resonance imaging (fMRI) is frequently used to localize language areas in a non-invasive manner. Various paradigms for presurgical localization of language areas have been developed, but a systematic quantitative evaluation of the efficiency of those paradigms has not been performed. In the present study, the authors analyzed different language paradigms to see which paradigm is most efficient in localizing frontal language areas. Five men and five women with no neurological deficits participated (mean age, 24 years) in this study. All volunteers were right-handed. Each subject performed 4 tasks, including fixation (Fix), sentence reading (SR), pseudoword reading (PR), and word generation (WG). Fixation and pseudoword reading were used as contrasts. The functional area was defined as the area(s) with a t-value of more than 3.92 in fMRI with different tasks. To apply an anatomical constraint, we used a brain atlas mapping system, which is available in AFNI, to define the anatomical frontal language area. The numbers of voxels in overlapped area between anatomical and functional area were individually counted in the frontal expressive language area. Of the various combinations, the word generation task was most effective in delineating the frontal expressive language area when fixation was used as a contrast (plocalizing Broca's area was 81% and specificity was 70%. Word generation versus fixation could effectively and reliably delineate the frontal language area. A customized effective paradigm should be analyzed in order to evaluate various language functions.

  9. Localization of Transversal Cracks in Sandwich Beams and Evaluation of Their Severity

    Directory of Open Access Journals (Sweden)

    G. R. Gillich

    2014-01-01

    Full Text Available An algorithm to assess transversal cracks in composite structures based on natural frequency changes due to damage is proposed. The damage assessment is performed in two steps; first the crack location is found, and afterwards an evaluation of its severity is performed. The technique is based on a mathematical relation that provides the exact solution for the frequency changes of bending vibration modes, considering two terms. The first term is related to the strain energy stored in the beam, while the second term considers the increase of flexibility due to damage. Thus, it is possible to separate the problems of localization and severity assessment, which makes the localization process independent of the beams cross-section shape and boundary conditions. In fact, the process consists of comparing vectors representing the measured frequency shifts with patterns constructed using the mode shape curvatures of the undamaged beam. Once the damage is localized, the evaluation of its severity is made taking into account the global rigidity reduction. The damage identification algorithm was validated by experiments performed on numerous sandwich panel specimens.

  10. Evaluation of Local Wheat Cultivars Susceptibility to infection with Black Stem Rust

    International Nuclear Information System (INIS)

    Batta, Y.A.

    2007-01-01

    The present study was conducted to assess the susceptibility of seven local wheat cultivars from Palestine to infection with black stem rust caused by Puccinia graminis f. sp. tritici. Two techniques of disease inoculation were applied during bioassays: global inoculation of entire wheat plants with urediospores and localized inoculation with urediospores and localized inoculation with urediospores on wheat leaf-pieces incubated under humid conditions. Susceptibility of tested cultivars was evaluated according to disease scale based on number and size of typical unredial pustules that appeared after inoculation on entire plants or leaf pieces. Results obtained on bioassay of susceptibility and disease rating on entire plants indicated that Anbar, Kamata and Hetiya safra cultivars were the least susceptible to P. g. tritici infection, whereas Debiya beda cultivar was the most susceptible. The other tested cultivars such as Nab-El-Jama, sawda and Senf 870 were moderately susceptible. On leaf-pieces, Anbar and Kamatat were the least susceptible cultivars, whereas Debiya beda and Nab-El-Jamal were the most susceptible cultivars. The other tested cultivars such as Debiya swada, Senf 870 and Hetiya safra were moderately susceptible. Significant reductions were obtained for the size of unredial postules formed on leaf-pieces when inoculated in an unwounded state compared to the wounded indicating the importance of wounds during inoculation. The global results indicated the possibility of using above method of disease inoculating, scaling and rating for evaluation of wheat cultivars susceptibility for the eventual use in breeding program for resistant varieties in Palestine. (author)

  11. Evaluation of Forming Limit by the 3 Dimensional Local Bifurcation Theory

    International Nuclear Information System (INIS)

    Nishimura, Ryuichi; Nakazawa, Yoshiaki; Ito, Koichi; Uemura, Gen; Mori, Naomichi

    2007-01-01

    A theoretical prediction and evaluation method for the sheet metal formability is developed on the basis of the three-dimensional local bifurcation theory previously proposed by authors. The forming limit diagram represented on the plane defined by the ratio of stress component to work-hardening rate is perfectly independent of plastic strain history. The upper and the lower limit of the sheet formability are indicated by the 3D critical line and the Stoeren-Rice's critical line on this plane, respectively. In order to verify the above mentioned behavior of the proposed forming limit diagram, the experimental research is also conducted. From the standpoint of the mechanical instability theory, a new concept called instability factor is introduced. It represents a degree of acceleration by current stress for developing the local bifurcation mode toward a fracture. The instability factor provides a method to evaluate a forming allowance which is useful to appropriate identification for a forming limit and to optimize the forming condition. The proposed criterion provides not only the moment to initiate the necking but also the local bifurcation mode vector and the direction of necking line

  12. [Construction of abridged life table for health evaluation of local resident using Excel program].

    Science.gov (United States)

    Chen, Qingsha; Wang, Feng; Li, Xiaozhen; Yang, Jian; Yu, Shouyi; Hu, Jun

    2012-05-01

    To provide an easy computational tool for evaluating the health condition of local residents. An abridged life table was programmed by applying mathematical functions and formula in Excel program and tested with the real study data to evaluate the results computed. The Excel was capable of computing group death probability of age in the life table ((n)q(x)), number of survivors (l(x)), number of death ((n)d(x)), survival per person-year ((n)L(x)), survival total per person-year (T(x)) and life expectancy (e(x)). The calculated results were consistent with those by SAS. The abridged life table constructed using Microsoft Excel can conveniently and accurately calculate the relevant indices for evaluating the health condition of the residents.

  13. Evaluation of the ASCO Value Framework for Anticancer Drugs at an Academic Medical Center.

    Science.gov (United States)

    Wilson, Leslie; Lin, Tracy; Wang, Ling; Patel, Tanuja; Tran, Denise; Kim, Sarah; Dacey, Katie; Yuen, Courtney; Kroon, Lisa; Brodowy, Bret; Rodondi, Kevin

    2017-02-01

    Anticancer drug prices have increased by an average of 12% each year from 1996 to 2014. A major concern is that the increasing cost and responsibility of evaluating treatment options are being shifted to patients. This research compared 2 value-based pricing models that were being considered for use at the University of California, San Francisco (UCSF) Medical Center to address the growing burden of high-cost cancer drugs while improving patient-centered care. The Medication Outcomes Center (MOC) in the Department of Clinical Pharmacy, University of California, San Francisco (UCSF), School of Pharmacy focuses on assessing the value of medication-related health care interventions and disseminating findings to the UCSF Medical Center. The High Cost Oncology Drug Initiative at the MOC aims to assess and adopt tools for the critical assessment and amelioration of high-cost cancer drugs. The American Society of Clinical Oncology (ASCO) Value Framework (2016 update) and a cost-effectiveness analysis (CEA) framework were identified as potential tools for adoption. To assess 1 prominent value framework, the study investigators (a) asked 8 clinicians to complete the ASCO Value Framework for 11 anticancer medications selected by the MOC; (b) reviewed CEAs assessing the drugs; (c) generated descriptive statistics; and (d) analyzed inter-rater reliability, convergence validity, and ranking consistency. On the scale of -20 to 180, the mean ASCO net health benefit (NHB) total score across 11 drugs ranged from 7.6 (SD = 7.8) to 53 (SD = 9.8). The Kappa coefficient (κ) for NHB scores across raters was 0.11, which is categorized as "slightly reliable." The combined κ score was 0.22, which is interpreted as low to fair inter-rater reliability. Convergent validity indicates that the correlation between NHB scores and CEA-based incremental cost-effectiveness ratios (ICERs) was low (-0.215). Ranking of ICERs, ASCO scores, and wholesale acquisition costs indicated different results

  14. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

    Science.gov (United States)

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation

    International Nuclear Information System (INIS)

    Akkari, Alessandra C.S.; Papini, Juliana Z. Boava; Garcia, Gabriella K.; Franco, Margareth K.K. Dias; Cavalcanti, Leide P.; Gasperini, Antonio; Alkschbirs, Melissa Inger; Yokaichyia, Fabiano; Paula, Eneida de; Tófoli, Giovana R.; Araujo, Daniele R. de

    2016-01-01

    In this study, we reported the development and the physico-chemical characterization of poloxamer 407 (PL407) and poloxamer 188 (PL188) binary systems as hydrogels for delivering ropivacaine (RVC), as drug model, and investigate their use in infiltrative local anesthesia for applications on the treatment of post-operative pain. We studied drug-micelle interaction and micellization process by light scattering and differential scanning calorimetry (DSC), the sol-gel transition and hydrogel supramolecular structure by small-angle-X-ray scattering (SAXS) and morphological evaluation by Scanning Electron Microscopy (SEM). In addition, we have presented the investigation of drug release mechanisms, in vitro/in vivo toxic and analgesic effects. Micellar dimensions evaluation showed the formation of PL407-PL188 mixed micelles and the drug incorporation, as well as the DSC studies showed increased enthalpy values for micelles formation after addition of PL 188 and RVC, indicating changes on self-assembly and the mixed micelles formation evoked by drug incorporation. SAXS studies revealed that the phase organization in hexagonal structure was not affected by RVC insertion into the hydrogels, maintaining their supramolecular structure. SEM analysis showed similar patterns after RVC addition. The RVC release followed the Higuchi model, modulated by the PL final concentration and the insertion of PL 188 into the system. Furthermore, the association PL407-PL188 induced lower in vitro cytotoxic effects, increased the duration of analgesia, in a single-dose model study, without evoking in vivo inflammation signs after local injection. - Highlights: • We present the development and relationships between physico-chemical and biopharmaceutical/pharmacological parameters for the PL407-PL188 binary hydrogel, as well as its use for infiltrative local anesthesia • The addition of PL188 and RVC evoked changes on enthalpy values, self-assembly and the mixed micelles formation • The

  16. Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Akkari, Alessandra C.S. [Human and Natural Sciences Center, ABC Federal University, Santo André, SP (Brazil); Papini, Juliana Z. Boava [São Francisco University, Bragança Paulista, São Paulo (Brazil); Garcia, Gabriella K. [Human and Natural Sciences Center, ABC Federal University, Santo André, SP (Brazil); Franco, Margareth K.K. Dias [Nuclear and Energy Research Institute, São Paulo, SP (Brazil); Cavalcanti, Leide P. [School of Chemical Engineering, University of Campinas, SP (Brazil); Gasperini, Antonio; Alkschbirs, Melissa Inger [Brazilian Synchrotron Light Laboratory, Campinas, SP (Brazil); Yokaichyia, Fabiano [Department Quantum Phenomena in Novel Materials Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Berlin (Germany); Paula, Eneida de [Department of Biochemistry, Institute of Biology, State University of Campinas, Campinas, SP (Brazil); Tófoli, Giovana R. [Faculty of Dentistry São Leopoldo Mandic, Campinas, São Paulo (Brazil); Araujo, Daniele R. de, E-mail: daniele.araujo@ufabc.edu.br [Human and Natural Sciences Center, ABC Federal University, Santo André, SP (Brazil)

    2016-11-01

    In this study, we reported the development and the physico-chemical characterization of poloxamer 407 (PL407) and poloxamer 188 (PL188) binary systems as hydrogels for delivering ropivacaine (RVC), as drug model, and investigate their use in infiltrative local anesthesia for applications on the treatment of post-operative pain. We studied drug-micelle interaction and micellization process by light scattering and differential scanning calorimetry (DSC), the sol-gel transition and hydrogel supramolecular structure by small-angle-X-ray scattering (SAXS) and morphological evaluation by Scanning Electron Microscopy (SEM). In addition, we have presented the investigation of drug release mechanisms, in vitro/in vivo toxic and analgesic effects. Micellar dimensions evaluation showed the formation of PL407-PL188 mixed micelles and the drug incorporation, as well as the DSC studies showed increased enthalpy values for micelles formation after addition of PL 188 and RVC, indicating changes on self-assembly and the mixed micelles formation evoked by drug incorporation. SAXS studies revealed that the phase organization in hexagonal structure was not affected by RVC insertion into the hydrogels, maintaining their supramolecular structure. SEM analysis showed similar patterns after RVC addition. The RVC release followed the Higuchi model, modulated by the PL final concentration and the insertion of PL 188 into the system. Furthermore, the association PL407-PL188 induced lower in vitro cytotoxic effects, increased the duration of analgesia, in a single-dose model study, without evoking in vivo inflammation signs after local injection. - Highlights: • We present the development and relationships between physico-chemical and biopharmaceutical/pharmacological parameters for the PL407-PL188 binary hydrogel, as well as its use for infiltrative local anesthesia • The addition of PL188 and RVC evoked changes on enthalpy values, self-assembly and the mixed micelles formation • The

  17. Evaluation of Risk Versus Benefit Information in Direct-To-Consumer (DTC) Prescription Drug Television Advertisements.

    Science.gov (United States)

    Fahim, Germin; Toscani, Michael; Barone, Joseph A; Wang, Chris; Gandhi, Shivani

    2018-01-01

    The FDA's Presenting Risk Information draft guidance from May 2009 states that the time of risk versus benefit is a factor taken into consideration when evaluating audio and video direct-to-consumer (DTC) broadcasts. The objective of the study is to evaluate the proportion of risk narration on television (TV) advertisements in comparison to the actual proportion of serious adverse effects findings across select therapeutic areas. The study reviews prescription drug TV advertisements between the years 2010 and 2015 separated by therapeutic class. Indicators to assess risk versus benefit are as follows: total benefit time, total risk time, total ad time, percentage proportion of risk, and number of serious adverse effects (SAEs) listed in the package insert. The objective is establishing proportion of risk-to-benefit narration across therapeutic areas and the proportion of risk narration compared to the number of SAEs in the package insert. These outcomes will reflect whether TV advertisements abide by the "fair balance" rule and if the time spent on risk narrations is proportional to the number of SAEs across therapeutic areas. An analysis of risk versus benefit showed that there was a vast range of percentage differences in risk versus benefit narration across the products selected. The majority of the products narrated showed a 40% to 60% risk-to-benefit ratio. Six out of the 10 products evaluated communicated applicable black box warnings. There was variability among the SAE percentages presented between products. Lack of consistency exists between risks versus benefit proportions among different drug products.

  18. Evaluation of secure capability-based access control in the M2M local cloud platform

    DEFF Research Database (Denmark)

    Anggorojati, Bayu; Prasad, Neeli R.; Prasad, Ramjee

    2016-01-01

    delegation. Recently, the capability based access control has been considered as method to manage access in the Internet of Things (IoT) or M2M domain. In this paper, the implementation and evaluation of a proposed secure capability based access control in the M2M local cloud platform is presented......Managing access to and protecting resources is one of the important aspect in managing security, especially in a distributed computing system such as Machine-to-Machine (M2M). One such platform known as the M2M local cloud platform, referring to BETaaS architecture [1], which conceptually consists...... of multiple distributed M2M gateways, creating new challenges in the access control. Some existing access control systems lack in scalability and flexibility to manage access from users or entity that belong to different authorization domains, or fails to provide fine grained and flexible access right...

  19. Presurgical language localization with visual naming associated ECoG high- gamma modulation in pediatric drug-resistant epilepsy.

    Science.gov (United States)

    Arya, Ravindra; Wilson, J Adam; Fujiwara, Hisako; Rozhkov, Leonid; Leach, James L; Byars, Anna W; Greiner, Hansel M; Vannest, Jennifer; Buroker, Jason; Milsap, Griffin; Ervin, Brian; Minai, Ali; Horn, Paul S; Holland, Katherine D; Mangano, Francesco T; Crone, Nathan E; Rose, Douglas F

    2017-04-01

    This prospective study compared presurgical language localization with visual naming-associated high-γ modulation (HGM) and conventional electrical cortical stimulation (ECS) in children with intracranial electrodes. Patients with drug-resistant epilepsy who were undergoing intracranial monitoring were included if able to name pictures. Electrocorticography (ECoG) signals were recorded during picture naming (overt and covert) and quiet baseline. For each electrode the likelihood of high-γ (70-116 Hz) power modulation during naming task relative to the baseline was estimated. Electrodes with significant HGM were plotted on a three-dimensional (3D) cortical surface model. Sensitivity, specificity, and accuracy were calculated compared to clinical ECS. Seventeen patients with mean age of 11.3 years (range 4-19) were included. In patients with left hemisphere electrodes (n = 10), HGM during overt naming showed high specificity (0.81, 95% confidence interval [CI] 0.78-0.85), and accuracy (0.71, 95% CI 0.66-0.75, p oral motor function was regarded as the gold standard. Similar results were reproduced by comparing covert naming-associated HGM with ECS naming sites. With right hemisphere electrodes (n = 7), no ECS-naming deficits were seen without interference with oral-motor function. HGM mapping showed a high specificity (0.81, 95% CI 0.78-0.84), and accuracy (0.76, 95% CI 0.71-0.81, p = 0.006), but modest sensitivity (0.44) compared to ECS interference with oral-motor function. Naming-associated ECoG HGM was consistently observed over Broca's area (left posterior inferior-frontal gyrus), bilateral oral/facial motor cortex, and sometimes over the temporal pole. This study supports the use of ECoG HGM mapping in children in whom adverse events preclude ECS, or as a screening method to prioritize electrodes for ECS testing. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  20. Mid-Term Assessment of the EU Drugs Strategy 2013-2020 and Final Evaluation of the Action Plan on Drugs 2013-2016: Final report.

    Science.gov (United States)

    Emilie, Balbirnie; Matthew, Davies; Emma, Disley; Cristina Gonzalez, Monsalve; Stephen, Hartka; Stijn, Hoorens; Kristy, Kruithof; Martin, Sacher; Jirka, Taylor

    2018-01-01

    The aim of the EU Drugs Strategy 2013-2020 is to contribute to a reduction in drug demand and drug supply within the EU. The Strategy has so far been implemented by an Action Plan covering the period 2013-2016. This article sets out the findings of an evaluation that assesses the degree of implementation of the Strategy and the Action Plan in terms of outputs and, where possible, impacts. It looks at the extent to which the objectives of the Strategy have been achieved. The evaluation aims to provide evidence to support the European Commission's decision about whether to propose a new Action Plan for the period 2017-2020 and, if so, what changes would be needed compared to the current plan. Through applying a mixed-methods approach, the evaluation examined the effectiveness, efficiency, relevance and coherence of the actions undertaken on the basis of the EU Drugs Strategy and the Action Plan, as well as their EU added value. The evaluation makes 20 recommendations, addressed to the European Commission, Member States, the European Council and other stakeholders. The key recommendation for the Commission is that a new Action Plan should be implemented for the period 2017-2020. This should be an updated version of the current Action Plan, rather than taking a new approach or introducing more new actions.

  1. A national drug related problems database: evaluation of use in practice, reliability and reproducibility

    DEFF Research Database (Denmark)

    Kjeldsen, Lene Juel; Birkholm, Trine; Fischer, Hanne Lis

    2014-01-01

    Background A drug related problems database (DRP-database) was developed on request by clinical pharmacists. The information from the DRP-database has only been used locally e.g. to identify focus areas and to communicate identified DRPs to the hospital wards. Hence the quality of the data...... by clinical pharmacists with categorization performed by the project group. Reproducibility was explored by re-categorization of a sample of existing records in the DRP-database by two project group members individually. Main outcome measures Observed proportion of agreement and Fleiss' kappa as measures...... reliability study of 34 clinical pharmacists showed high inter-rater reliability with the project group (Fleiss' kappa = 0.79 with 95 % CI (0.70; 0.88)), and the reproducibility study also documented high inter-rater reliability of a sample of 379 records from the DRP-database re-categorized by two project...

  2. Influence of local air velocity from air conditioner evaluated by salivary and skin biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Masaki; Takahashi, Takayuki; Yoshino, Yuichiro; Sasaki, Makoto [Graduate School of Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551 (Japan); Nishimiya, Hajime [Asahi Kasei Homes Corporation, R and D Laboratories, 2-1 Samejima, Fuji, Shizuoka 416-8501 (Japan)

    2010-11-15

    The purpose of this paper is to reveal both the psychosomatic and the physical effects of local air velocity from an air conditioner using biomarkers which can be collected noninvasively. Salivary {alpha}-amylase activity (SAA) and salivary cortisol were used as the indexes of psychosomatic effects. The total protein (TP) collected from stratum corneum was used as an index of the physical condition of dry skin. A continuous experiment over a 5 days period in summer was conducted using 8 healthy young male adults for 2-types of airflow conditioners, a whole ceiling-type air conditioner (without local air velocity) and a normal-type air conditioner (with local air velocity). The subjects felt cool, windy, dry and uncomfortable when under the normal-type air conditioner as determined in a subjective evaluation. The SAA under the normal-type air conditioner fluctuated more widely than with the whole ceiling-type air conditioner. The level of salivary cortisol decreased more in a day under the normal-type air conditioner than with the whole ceiling-type air conditioner. These results showed that reducing local air velocity may provide more healthy psychosomatic conditions over the long-term. Moreover, the TP of a drying-exposed skin area showed a significant change during this experiment whereas the TP of drying-protected area was relatively unchanged. It was indicated that one week's exposure to local air velocity conditions possibly influences the drying of facial skin. Thus, air movement at low velocity can be provides more comfortable conditions not only psychosomatically but also physically. (author)

  3. MRI evaluation following partial HIFU therapy for localized prostate cancer: A single-center study.

    Science.gov (United States)

    Hoquetis, L; Malavaud, B; Game, X; Beauval, J B; Portalez, D; Soulie, M; Rischmann, P

    2016-09-01

    To evaluate the value of MRI for surveillance of primary hemi-HIFU therapy for localized PCa in a single-center. Patients with localized prostate cancer were treated with hemi-HIFU from October 2009 to March 2014. All patients performed MRI before focal therapy, the reader was blinded to the treatment. Oncological failure was defined as positive biopsy or biochemical recurrence (Phoenix). Twenty-five patients were treated with hemi-HIFU in one center. The median nadir PSA was 1.45±1.4ng/mL. Prostate volume decreased from 45 cc to 25 cc on MRI findings. At 20 months, none of the patients had histological recurrence. Biochemical-free survival rate was 88%. MRI evaluation had a negative predictive value of 100% on the treated area and 81% on the untreated area. PSAd≥0.1ng/mL(2) was a predictive factor for cancer on untreated area (P=0.042). MRI control at 6 months is a potentially effective evaluation of treated area after hemi-HIFU and may replace randomized biopsies if PSAd<0.1ng/mL(2) during follow-up. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Comparison between continuous and localized methods to evaluate the flow rate through containment concrete structures

    Energy Technology Data Exchange (ETDEWEB)

    Jason, L., E-mail: ludovic.jason@cea.fr [Atomic Energy Commission (CEA), DEN, DANS, DM2S, SEMT, Mechanics and System Simulation Laboratory (LM2S), F-91191 Gif sur Yvette (France); LaMSID, UMR CNRS-EDF-CEA 8193, F-92141 Clamart (France); Masson, B. [Electricité de France (EDF), SEPTEN, F-69628 Villeurbanne (France)

    2014-10-01

    Highlights: • The contribution focuses on the gas transfer through reinforced concrete structures. • A continuous approach with a damage–permeability law is investigated. • It is significant, for this case, only when the damage variable crosses the section. • In this case, two localized approaches are compared. • It helps at evaluating a “reference” crack opening for engineering laws. - Abstract: In this contribution, different techniques are compared to evaluate the gas flow rate through a representative section of a reinforced and prestressed concrete containment structure. A continuous approach is first applied which is based on the evaluation of the gas permeability as a function of the damage variable. The calculations show that the flow rate becomes significant only when the damage variable crosses the section. But in this situation, the continuous approach is no longer fully valid. That is why localized approaches, based on a fine description of the crack openings, are then investigated. A comparison between classical simplified laws (Poiseuille flow) and a more refined model which takes into account the evolution of the crack opening in the depth of the section enables to define the validity domain of the simplified laws and especially the definition of the associated “reference opening”.

  5. Macrophage models of Gaucher disease for evaluating disease pathogenesis and candidate drugs.

    Science.gov (United States)

    Aflaki, Elma; Stubblefield, Barbara K; Maniwang, Emerson; Lopez, Grisel; Moaven, Nima; Goldin, Ehud; Marugan, Juan; Patnaik, Samarjit; Dutra, Amalia; Southall, Noel; Zheng, Wei; Tayebi, Nahid; Sidransky, Ellen

    2014-06-11

    Gaucher disease is caused by an inherited deficiency of glucocerebrosidase that manifests with storage of glycolipids in lysosomes, particularly in macrophages. Available cell lines modeling Gaucher disease do not demonstrate lysosomal storage of glycolipids; therefore, we set out to develop two macrophage models of Gaucher disease that exhibit appropriate substrate accumulation. We used these cellular models both to investigate altered macrophage biology in Gaucher disease and to evaluate candidate drugs for its treatment. We generated and characterized monocyte-derived macrophages from 20 patients carrying different Gaucher disease mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived macrophages from five fibroblast lines taken from patients with type 1 or type 2 Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed reduced glucocerebrosidase activity and increased storage of glucocerebroside and glucosylsphingosine in lysosomes. These macrophages showed efficient phagocytosis of bacteria but reduced production of intracellular reactive oxygen species and impaired chemotaxis. The disease phenotype was reversed with a noninhibitory small-molecule chaperone drug that enhanced glucocerebrosidase activity in the macrophages, reduced glycolipid storage, and normalized chemotaxis and production of reactive oxygen species. Macrophages differentiated from patient monocytes or patient-derived iPSCs provide cellular models that can be used to investigate disease pathogenesis and facilitate drug development. Copyright © 2014, American Association for the Advancement of Science.

  6. Evaluations of imidazolium ionic liquids as novel skin permeation enhancers for drug transdermal delivery.

    Science.gov (United States)

    Zhang, Ding; Wang, Huai-Ji; Cui, Xiu-Ming; Wang, Cheng-Xiao

    2017-06-01

    In this work, imidazolium ionic liquids (imidazolium ILs) were employed as the novel chemical permeation enhancers (CPEs) and their performances and mechanisms of action were deeply investigated. Testosterone was used as a model drug to investigate the transdermal delivery enhancement of twenty imdidazolium ILs. The results suggested that the promotion activity connected to the structure and composition of the ILs. The quantitative structure-activity relationship (QSAR) model revealed a good linearity between the electronic properties of ILs and their enhancements. Furthermore, the transepidermal water loss (TEWL) and scanning laser confocal microscope (CLSM) examinations showed the strong improvement of ILs on skin barrier permeability, which were well correlated with the drug penetration profiles. The total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscope (AFM) evaluations of skins indicated that the ILs can disrupt the regular and compact arrangements of the corneocytes, change the surface properties of stratum corneum, and make the skin structure more permeable. Our work demonstrated the significant skin permeation promotion profiles of the imidazolium ILs, which are of great potential in transdermal drug delivery systems.

  7. Calcium antagonistic effects of Chinese crude drugs: Preliminary investigation and evaluation by 45Ca

    International Nuclear Information System (INIS)

    Liu Ning; Yang Yuanyou; Mo Shangwu; Liao Jiali; Jin Jiannan

    2005-01-01

    Coronary and other diseases in cardiac or brain blood vessels are considered to be due to the excessive influx of Ca 2+ into cytoplasm. If Ca 2+ channels in cell membrane are blocked by medicines or other substances with considerable calcium antagonistic effects, these diseases might be cured or controlled. The influence of some Chinese crude drugs, including Crocus sativus, Carthamus tinctorius, Ginkgo biloba and Bulbus allii macrostemi on Ca 2+ influx in isolated rat aortas was investigated by using 45 Ca as a radioactive tracer, and their calcium antagonistic effects were evaluated. It can be noted that Ca 2+ uptake in isolated rat aorta rings in normal physiological status was not markedly altered by these drugs, whereas the Ca 2+ influxes induced by norepinephrine of 1.2 μmol/L and KCl of 100 mmol/L were significantly inhibited by Crocus, Carthamus and Bulbus in a concentration-dependent manner, but not by Ginkgo. The results show that extracellular Ca 2+ influx through receptor-operated Ca 2+ channels and potential-dependent Ca 2+ channels can be blocked by Crocus, Carthamus and Bulbus. This implies that these Chinese crude drugs have obvious calcium antagonistic effects

  8. Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine.

    Science.gov (United States)

    Chintalapudi, Ramprasad; Murthy, T E G K; Lakshmi, K Rajya; Manohar, G Ganesh

    2015-01-01

    The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 2(2) factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 2(2) factorial designs. The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology.

  9. Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

    Science.gov (United States)

    Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

    2015-12-01

    Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

  10. A Performance/Cost Evaluation for a GPU-Based Drug Discovery Application on Volunteer Computing

    Science.gov (United States)

    Guerrero, Ginés D.; Imbernón, Baldomero; García, José M.

    2014-01-01

    Bioinformatics is an interdisciplinary research field that develops tools for the analysis of large biological databases, and, thus, the use of high performance computing (HPC) platforms is mandatory for the generation of useful biological knowledge. The latest generation of graphics processing units (GPUs) has democratized the use of HPC as they push desktop computers to cluster-level performance. Many applications within this field have been developed to leverage these powerful and low-cost architectures. However, these applications still need to scale to larger GPU-based systems to enable remarkable advances in the fields of healthcare, drug discovery, genome research, etc. The inclusion of GPUs in HPC systems exacerbates power and temperature issues, increasing the total cost of ownership (TCO). This paper explores the benefits of volunteer computing to scale bioinformatics applications as an alternative to own large GPU-based local infrastructures. We use as a benchmark a GPU-based drug discovery application called BINDSURF that their computational requirements go beyond a single desktop machine. Volunteer computing is presented as a cheap and valid HPC system for those bioinformatics applications that need to process huge amounts of data and where the response time is not a critical factor. PMID:25025055

  11. A Performance/Cost Evaluation for a GPU-Based Drug Discovery Application on Volunteer Computing

    Directory of Open Access Journals (Sweden)

    Ginés D. Guerrero

    2014-01-01

    Full Text Available Bioinformatics is an interdisciplinary research field that develops tools for the analysis of large biological databases, and, thus, the use of high performance computing (HPC platforms is mandatory for the generation of useful biological knowledge. The latest generation of graphics processing units (GPUs has democratized the use of HPC as they push desktop computers to cluster-level performance. Many applications within this field have been developed to leverage these powerful and low-cost architectures. However, these applications still need to scale to larger GPU-based systems to enable remarkable advances in the fields of healthcare, drug discovery, genome research, etc. The inclusion of GPUs in HPC systems exacerbates power and temperature issues, increasing the total cost of ownership (TCO. This paper explores the benefits of volunteer computing to scale bioinformatics applications as an alternative to own large GPU-based local infrastructures. We use as a benchmark a GPU-based drug discovery application called BINDSURF that their computational requirements go beyond a single desktop machine. Volunteer computing is presented as a cheap and valid HPC system for those bioinformatics applications that need to process huge amounts of data and where the response time is not a critical factor.

  12. Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

    Science.gov (United States)

    Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

    2003-07-01

    The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of

  13. Distributed Evaluation of Local Sensitivity Analysis (DELSA), with application to hydrologic models

    Science.gov (United States)

    Rakovec, O.; Hill, M. C.; Clark, M. P.; Weerts, A. H.; Teuling, A. J.; Uijlenhoet, R.

    2014-01-01

    This paper presents a hybrid local-global sensitivity analysis method termed the Distributed Evaluation of Local Sensitivity Analysis (DELSA), which is used here to identify important and unimportant parameters and evaluate how model parameter importance changes as parameter values change. DELSA uses derivative-based "local" methods to obtain the distribution of parameter sensitivity across the parameter space, which promotes consideration of sensitivity analysis results in the context of simulated dynamics. This work presents DELSA, discusses how it relates to existing methods, and uses two hydrologic test cases to compare its performance with the popular global, variance-based Sobol' method. The first test case is a simple nonlinear reservoir model with two parameters. The second test case involves five alternative "bucket-style" hydrologic models with up to 14 parameters applied to a medium-sized catchment (200 km2) in the Belgian Ardennes. Results show that in both examples, Sobol' and DELSA identify similar important and unimportant parameters, with DELSA enabling more detailed insight at much lower computational cost. For example, in the real-world problem the time delay in runoff is the most important parameter in all models, but DELSA shows that for about 20% of parameter sets it is not important at all and alternative mechanisms and parameters dominate. Moreover, the time delay was identified as important in regions producing poor model fits, whereas other parameters were identified as more important in regions of the parameter space producing better model fits. The ability to understand how parameter importance varies through parameter space is critical to inform decisions about, for example, additional data collection and model development. The ability to perform such analyses with modest computational requirements provides exciting opportunities to evaluate complicated models as well as many alternative models.

  14. Batch-to-Batch Quality Consistency Evaluation of Botanical Drug Products Using Multivariate Statistical Analysis of the Chromatographic Fingerprint

    OpenAIRE

    Xiong, Haoshu; Yu, Lawrence X.; Qu, Haibin

    2013-01-01

    Botanical drug products have batch-to-batch quality variability due to botanical raw materials and the current manufacturing process. The rational evaluation and control of product quality consistency are essential to ensure the efficacy and safety. Chromatographic fingerprinting is an important and widely used tool to characterize the chemical composition of botanical drug products. Multivariate statistical analysis has showed its efficacy and applicability in the quality evaluation of many ...

  15. Preparation and Evaluation of Taste Masked Famotidine Formulation Using Drug/β-cyclodextrin/Polymer Ternary Complexation Approach

    OpenAIRE

    Patel, Ashok R.; Vavia, Pradeep R.

    2008-01-01

    The main aim of the present study was to evaluate potential of ternary complexation (comprising of drug, cyclodextrin and polymer) as an approach for taste masking. For this purpose famotidine with property of bitter taste was selected as a model drug. Improvement in taste masking capability of cyclodextrin towards famotidine was evaluated by formulating a ternary complex including hydrophilic polymer hydroxyl propyl methyl cellulose (HPMC 5 cps) as the third component. Phase solubility analy...

  16. Evaluation of Drug-Drug Interaction Potential Between Sacubitril/Valsartan (LCZ696) and Statins Using a Physiologically Based Pharmacokinetic Model.

    Science.gov (United States)

    Lin, Wen; Ji, Tao; Einolf, Heidi; Ayalasomayajula, Surya; Lin, Tsu-Han; Hanna, Imad; Heimbach, Tycho; Breen, Christopher; Jarugula, Venkateswar; He, Handan

    2017-05-01

    Sacubitril/valsartan (LCZ696) has been approved for the treatment of heart failure. Sacubitril is an in vitro inhibitor of organic anion-transporting polypeptides (OATPs). In clinical studies, LCZ696 increased atorvastatin C max by 1.7-fold and area under the plasma concentration-time curve by 1.3-fold, but had little or no effect on simvastatin or simvastatin acid exposure. A physiologically based pharmacokinetics modeling approach was applied to explore the underlying mechanisms behind the statin-specific LCZ696 drug interaction observations. The model incorporated OATP-mediated clearance (CL int,T ) for simvastatin and simvastatin acid to successfully describe the pharmacokinetic profiles of either analyte in the absence or presence of LCZ696. Moreover, the model successfully described the clinically observed drug effect with atorvastatin. The simulations clarified the critical parameters responsible for the observation of a low, yet clinically relevant, drug-drug interaction DDI between sacubitril and atorvastatin and the lack of effect with simvastatin acid. Atorvastatin is administered in its active form and rapidly achieves C max that coincide with the low C max of sacubitril. In contrast, simvastatin requires a hydrolysis step to the acid form and therefore is not present at the site of interactions at sacubitril concentrations that are inhibitory. Similar models were used to evaluate the drug-drug interaction risk for additional OATP-transported statins which predicted to maximally result in a 1.5-fold exposure increase. Copyright © 2017. Published by Elsevier Inc.

  17. The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

    Science.gov (United States)

    Horii, Ikuo

    2016-01-01

    Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision

  18. Comparative evaluation of radiation injuries in skin histological structures under local irradiation

    International Nuclear Information System (INIS)

    Kolchanova, G.M.

    1978-01-01

    In order to evaluate quantitatively to what degree the various histologic structures of the skin undergo changes after a radiation injury and during the reparative process, white rats have been used to study these changes in relation to the radiation dose and the time elapsed after exposure. The rats have been locally exposed on a single occasion to long-wave (10.2 keV) x-radiation in doses of 250, 500, 1000, or 2000 R. Greatest changes in histologic structures occured with doses of 250-1000 R on days 96-115 postexposure. With higher doses, these changes are most clearly marked as early as on day 38

  19. Conformal radiation therapy of localized prostate cancer: acute tolerance and early evaluation of effectiveness

    International Nuclear Information System (INIS)

    Zierhut, D.; Flentje, M.; Sroka-Perez, G.; Rudat, V.; Engenhart-Cabillic, R.; Wannenmacher, M.

    1997-01-01

    Aim: In a prospective trial early effectiveness and acute toxicity of conformal 3D-planned radiotherapy for localized prostate cancer was quantified using dose-volume-histogramms and evaluated with respect of treatment technique. Results: Eleven patients (of 32) had none, 15 mild (RTOG grade 1) and 6 moderate symptoms (RTOG grade 2, mainly diarrhoea, dysuria and polyuria). Acute complications leading to treatment interruption did not occur. In 16 patients symptoms disappeared within 6 weeks after radiotherapy. Only 2 men had symptoms which lasted longer than 3 months and were endoscopically examined. Up to now no late complications were detected. Incidence and severity of toxicity was significantly (p [de

  20. IN VITRO MODELS TO EVALUATE DRUG-INDUCED HYPERSENSITIVITY: POTENTIAL TEST BASED ON ACTIVATION OF DENDRITIC CELLS

    Directory of Open Access Journals (Sweden)

    Valentina Galbiati

    2016-07-01

    Full Text Available Hypersensitivity drug reactions (HDRs are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ('allergic' and non immune-mediated ('pseudo allergic' reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon.We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells.

  1. Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

    Science.gov (United States)

    Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

    2010-01-01

    Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

  2. Performance evaluation of enzyme immunoassay for voriconazole therapeutic drug monitoring with automated clinical chemistry analyzers

    Directory of Open Access Journals (Sweden)

    Yongbum Jeon

    2017-08-01

    Full Text Available Objective: Voriconazole is a triazole antifungal developed for the treatment of fungal infectious disease, and the clinical utility of its therapeutic drug monitoring has been evaluated. Recently, a new assay for analyzing the serum voriconazole concentration with an automated clinical chemistry analyzer was developed. We evaluated the performance of the new assay based on standardized protocols. Methods: The analytical performance of the assay was evaluated according to its precision, trueness by recovery, limit of quantitation, linearity, and correlation with results from liquid chromatography-tandem mass spectrometry (LC-MS/MS. The evaluation was performed with the same protocol on two different routine chemistry analyzers. All evaluations were performed according to CLSI Guidelines EP15, EP17, EP6, and EP9 [1–4]. Results: Coefficients of variation for within-run and between-day imprecision were 3.2–5.1% and 1.5–3.0%, respectively, on the two different analyzers for pooled serum samples. The recovery rates were in the range of 95.4–102.2%. The limit of blank was 0.0049 μg/mL, and the limit of detection of the samples was 0.0266–0.0376 μg/mL. The percent recovery at three LoQ levels were 67.9–74.6% for 0.50 μg/mL, 75.5–80.2% for 0.60 μg/mL, and 89.9–96.6% for 0.70 μg/mL. A linear relationship was demonstrated between 0.5 μg/mL and 16.0 μg/mL (R2=0.9995–0.9998. The assay correlated well with LC-MS/MS results (R2=0.9739–0.9828. Conclusions: The assay showed acceptable precision, trueness, linearity, and limit of quantification, and correlated well with LC-MS/MS. Therefore, its analytical performance is satisfactory for monitoring the drug concentration of voriconazole. Keywords: Voriconazole, Antifungal agents, Therapeutic drug monitoring

  3. Creative Destruction: Next Generation Sequencing in Drug Development, Formulary Evaluations and Pricing

    Directory of Open Access Journals (Sweden)

    Paul C Langley

    2016-11-01

    Full Text Available Next generation sequencing (NGS has the potential to disrupt not only the accepted process of drug development but also the hurdles a drug manufacturer would be expected to face in securing formulary approval and a possible premium price for the new compound. The purpose of this commentary is to consider the role of NGS in this process, one which is characterized as a process of creative destruction, where adoption of NGS in personalized medicine sets in train a mechanism of incessant product and process review. A mechanism driven by continuing modifications and extensions to NGS platforms as our understanding of the role of mutations and mutation load in therapy choice expands. At the same time this mechanism has significant implications for the continued revision of treatment guidelines and their adoption of NGS as integral parts of the treatment pathway. There are, however, a number of unresolved issues which have to be addressed. These include the choice of NGS platform, barriers to integrating evidence to support NGS-based therapy choices in treatment guidelines, the implications of NGS for drug development and the modification or rejection of current trial structures, the integration of comorbid disease states and the standards that formulary committees should adopt to evaluate NGS claims. The overarching theme, however, is the need to invest in a robust and credible evidence base. While we are a long way from achieving this, the focus must be on putting claims for therapy choice forward that are credible, evaluable and replicable.   Type: Commentary

  4. Preclinical quantitative MicroPET imaging in evaluation of neuroprotective drug candidates

    International Nuclear Information System (INIS)

    Son, Ji Yeon; Kim, Yu Kyeong; Kim, Ji Sun; Lee, Byung Chul; Kim, Kyeong Min; Choi, Tae Hyun; Cheon, Gi Jeong; Lee, Won Woo; Kim, Sang Eun

    2007-01-01

    Using in vivo molecular imaging with microPET/SPECT has been expected to facilitate drug discovery and development. In this study, we applied quantitative microPET to the preclinical evaluation of the effects of two neuroprotective drug candidates to the nigrostriatal dopaminergic neuronal damage. Fifteen SD rats were divided into three groups. The rats of each group were orally administrated one of neuroprotective candidate; NeuProtec (100mg/kg bid) and SureCero (10mg/kg, qd) or normal saline (0.1ml, qd) for 3 weeks. 6-OHDA was sterotactically placed to the right striatum on eighth day after starting while continuing the medication for additional 14 days. [ 124 I]FP-ClT PET scans were obtained using microPET R4 scanner. The behavioral test by amphetamine-induced rotation and the histological examination after thyrosine hydroxylase (TH) immunohistochemical staining were performed. Different uptake in the lesioned striatum among the groups were demonstrated on [ 124 I]FP-CIT PET images. The rats with NeuProtec showed higher binding in the lesion than controls. No differences were observed in SureCere groups. The FP-CIT uptake in the lesioned striatum was well correlated with the % reduction of TH(+) cells (rho =0.73, p=0.025), and also correlated with rotation test (rho =0.79, p=0.001) [ 124 I]FP-CIT animal PET depicted the neuroprotective effects of NeuProtec to the 6-OHDA neurotoxicity in the rat striatum. No demonstrable effect of SureCero might indicate that inadequate dosage was used in this study. MicroPET imaging with small animal could be a great tool in preclinical evaluation of drug efficacy

  5. Evaluation of local muscle soreness treatment with anterior bite splint made of soft putty impression material

    Directory of Open Access Journals (Sweden)

    Harry Laksono

    2013-03-01

    Full Text Available Background: Local muscle soreness is the most common temporomandibular disorders complaint of patients seeking treatment in the dental clinics. The emergency treatment that can be done in the clinics to manage this disorder is by making anterior bite splint. Anterior bite splint is usually made of acrylic, but currently there is a soft putty impression material that can also be used for making anterior bite splint. The effectiveness of soft putty anterior bite splint in local muscle soreness treatment still has not clear. Purpose: To determine the effectiveness of the soft putty impression material as a material used for making anterior bite splint in the treatment of local muscle soreness. Case: Six patients was reported five female patients aged 20-40 years old and one male patient aged 37 years old with local muscle soreness. Four female patients with a “click” sound on TMJ. Case management: Make differential diagnosis with screening history (anamnesis, clinical examination consists of extra oral examination such as muscle and temporomandibular joint palpation, measure the mandibular movement, end-feel, load test, intra oral examination and radiographic evaluation. Record the results and make the diagnosis. Make a soft putty anterior bite splint, adjusted and inserted in the maxillary anterior teeth. Record the results based on signs and symptoms. Conclusion: It can be concluded that anterior bite splint made of soft putty impression material is effective for treatment the local muscle soreness.Latar belakang: Salah satu tipe temporomandibular disorders yang paling sering dijumpai di klinik dokter gigi adalah local muscle soreness. Perawatan yang dapat dengan segera dilakukan di klinik untuk mengelola gangguan tersebut adalah dengan pembuatan anterior bite splint. Biasanya anterior bite splint terbuat dari akrilik, namun saat ini telah ada bahan cetak soft putty yang memungkinkan untuk dipakai sebagai bahan pembuatan anterior bite splint

  6. Evaluation of the effect of localized skin cooling on nasal airway volume by acoustic rhinometry.

    Science.gov (United States)

    Yamagiwa, M; Hilberg, O; Pedersen, O F; Lundqvist, G R

    1990-04-01

    Ten healthy subjects (four men and six women) were subjected to localized skin cooling by submersion for 5 min of both feet and, in another experiment, one hand and forearm into ice-cold water. Repeated measurements of nasal cavity volumes by a new method, acoustic rhinometry, showed characteristic patterns ranging from marked increases in volumes lasting the entire exposure period to transient monophasic or biphasic responses to no change at all. The pattern in individual subjects was reproducible with the two methods of cooling, and it could be characterized by five types when related to baseline measurements during the preexposure period. Because of large minute-to-minute variations, probably determined by local differences and fluctuations in blood flow in tissues through the nose, evaluation of induced changes in the nasal cavity volume cannot be based on single measurements as has frequently been done in the past by using rhinomanometry as the experimental method. The mechanisms behind the characteristic patterns in immediate human nasal response to local skin cooling challenge remains to be explored.

  7. Evaluation of local stress for stress corrosion crack initiation by three-dimensional polycrystal model

    International Nuclear Information System (INIS)

    Kamaya, Masayuki; Kitamura, Takayuki

    2006-01-01

    In order to understand the initiation behavior of microstructurally small cracks in a stress corrosion cracking condition, it is important to know the tensile normal stress acting on the grain boundary (normal G.B. stress). The local stress in a polycrystalline body is greatly influenced by deformation constraint which is caused by anisotropic and/or inhomogeneous property of each grain. In present study, the local normal G.B. stress on bi- and tri-crystal bodies and a three-dimensional polycrystalline body consisting of 100 grains were evaluated by the finite element method under a remote uniform tensile stress condition. The polycrystalline body was generated by using a Monte Carlo procedure and random orientations were assigned to each grain. It was revealed that the local normal G.B. stress on the polycrystalline body is inhomogeneous under uniform applied stress. The stress tends to be large near the triple points due to the deformation constraint caused by adjacent grains, even though the grain boundary inclination to the load axis has large influence. It was also shown that particular high stress was not observed at corners of the polycrystalline body. (author)

  8. Evaluation of preoperative radiation combined with chemotherapy for prevention of local recurrence of rectal cancer

    International Nuclear Information System (INIS)

    Sarashina, Hiromi; Inoue, Ikuo; Saitoh, Norio

    1990-01-01

    A retrospective study of 44 patients with rectal cancer who received preoperative radiation (42.6 Gy) combined with chemotherapy and 37 who received resection alone (control group) was undertaken to evaluate the effect of preoperative radiation therapy on local recurrence of rectal cancer. The rate of local recurrence in the radiation group was reduced to 4.5% compared with that in the controls (18.9%). From a pathological point of view, factors that have a close association with recurrence, such as depth of invasion, ew (defined as the distance between the external surgical surface and the deepest site of invasion) and lymph nodal involvement, have been successfully changed after radiation therapy. It was also evident that the rate of recurrence in irradiated patients, depth of invasion of a 2 (defined as the invasion of cancer far beyond the muscle layer but without involvement of other organs) or ew less than 2 mm was significantly lower than in patients with the same pathological conditions in whom radiation was not used. However, especially in patients with remote lymph node metastasis, there was no difference in local recurrence rate between the two groups. From these findings, it was concluded that a careful follow up is necessary for patients with remote lymph node involvement even after radiation therapy. (author)

  9. Dosimetric evaluation of tomography and four-box field conformal radiotherapy in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Yu, Mina; Lee, Hyo Chun; Chung, Mi Joo; Kim, Sung Hwan; Lee, Jong Hoon; Jang, Hong Seok; Jeon, Dong Min; Cheon, Geum Seong

    2013-01-01

    To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer. Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, Vn Gy, Dmin, Dmax, radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose. Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p 0.001). But, V26.25 Gy and V27.5 Gywere not significantly different between the two modalities. Tomotherapy showed higher Dmax and lower Dmin. The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT. In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.

  10. Experimental evaluation of local bubble parameters of subcooled boiling flow in a pressurized vertical annulus channel

    Energy Technology Data Exchange (ETDEWEB)

    Chu, In-Cheol, E-mail: chuic@kaeri.re.kr; Lee, Seung-Jun; Youn, Young Jung; Park, Jong Kuk; Choi, Hae Seob; Euh, Dong-Jin; Song, Chul-Hwa

    2017-02-15

    Experiments were performed to quantify the local bubble parameters such as void fraction, bubble velocity, interfacial area concentration, and Sauter mean diameter for the subcooled boiling flow of a refrigerant R-134a in a pressurized vertical annulus channel. Optical fiber void probe and double pressure boundary visualization windows were installed at four measurement stations with different elevations, thus enabling the quantification of local bubble parameters and observation of global boiling structure. Using high-resolution traverse systems for the optical fiber void probes and the heating tube, the radial profiles of the bubble parameters and their axial propagation can be evaluated at any elevation of the whole heating region. At this first phase of the experiments, three tests were conducted by varying the pressure, heat flux, mass flux, and local liquid subcooling. The radial profiles of the bubble parameters were obtained at seven elevations. The pressure condition of the present experiments covered the normal operating pressure of PWRs according to the similarity criteria. The present experimental data will be useful for thorough validation and improvement of the CMFD (Computation Multi-Fluid Dynamics) codes and constitutive relations.

  11. Mobile Ground-Based Radar Sensor for Localization and Mapping: An Evaluation of two Approaches

    Directory of Open Access Journals (Sweden)

    Damien Vivet

    2013-08-01

    Full Text Available This paper is concerned with robotic applications using a ground-based radar sensor for simultaneous localization and mapping problems. In mobile robotics, radar technology is interesting because of its long range and the robustness of radar waves to atmospheric conditions, making these sensors well-suited for extended outdoor robotic applications. Two localization and mapping approaches using data obtained from a 360° field of view microwave radar sensor are presented and compared. The first method is a trajectory-oriented simultaneous localization and mapping technique, which makes no landmark assumptions and avoids the data association problem. The estimation of the ego-motion makes use of the Fourier-Mellin transform for registering radar images in a sequence, from which the rotation and translation of the sensor motion can be estimated. The second approach uses the consequence of using a rotating range sensor in high speed robotics. In such a situation, movement combinations create distortions in the collected data. Velocimetry is achieved here by explicitly analysing these measurement distortions. As a result, the trajectory of the vehicle and then the radar map of outdoor environments can be obtained. The evaluation of experimental results obtained by the two methods is presented on real-world data from a vehicle moving at 30 km/h over a 2.5 km course.

  12. Dosimetric evaluation of tomography and four-box field conformal radiotherapy in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Mina; Lee, Hyo Chun; Chung, Mi Joo; Kim, Sung Hwan; Lee, Jong Hoon [Dept. of Radiation Oncology, St. Vincent' s Hospital, The Catholic University of Korea College of Medicine, Suwon (Korea, Republic of); Jang, Hong Seok; Jeon, Dong Min; Cheon, Geum Seong [Dept. of Radiation Oncology, Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer. Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, Vn Gy, Dmin, Dmax, radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose. Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p 0.001). But, V26.25 Gy and V27.5 Gywere not significantly different between the two modalities. Tomotherapy showed higher Dmax and lower Dmin. The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT. In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.

  13. Basic evaluation of typical nanoporous silica nanoparticles in being drug carrier: Structure, wettability and hemolysis.

    Science.gov (United States)

    Li, Jing; Guo, Yingyu

    2017-04-01

    Herein, the present work devoted to study the basic capacity of nanoporous silica nanoparticles in being drug carrier that covered structure, wettability and hemolysis so as to provide crucial evaluation. Typical nanoporous silica nanoparticles that consist of nanoporous silica nanoparticles (NSN), amino modified nanoporous silica nanoparticles (amino-NSN), carboxyl modified nanoporous silica nanoparticles (carboxyl-NSN) and hierachical nanoporous silica nanoparticles (hierachical-NSN) were studied. The results showed that their wettability and hemolysis were closely related to structure and surface modification. Basically, wettability became stronger as the amount of OH on the surface of NSN was higher. Both large nanopores and surface modification can reduce the wettability of NSN. Furthermore, NSN series were safe to be used when they circulated into the blood in low concentration, while if high concentration can not be avoided during administration, high porosity or amino modification of NSN were safer to be considered. It is believed that the basic evaluation of NSN can make contribution in providing scientific instruction for designing drug loaded NSN systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Evaluation of package inserts of Ayurveda drug formulations from Mumbai city.

    Science.gov (United States)

    Shirolkar, Sudatta; Tripathi, Raakhi K; Potey, Anirudha V

    2015-01-01

    Package insert (PI) is a vital document accompanying a prescribed medication to provide information to the prescriber and end-user at a glance. Studies regarding PIs of Ayurvedic medicines in accordance with standard guidelines are lacking. Present study was undertaken to evaluate PI of Ayurveda drugs. PIs of Ayurveda drugs were obtained from five randomly selected Ayurveda medical shops located in three main zones of Mumbai. From each medical shop, a range of 15-20 PI was planned to be collected for different formulations. It was decided to collect a minimum fifty PIs/group for equitable distribution of various formulations in period of January-June2013. Checklist was prepared, and content validity was achieved. Final validated checklist contained a total of 13 items, and the presence or absence of information pertaining to these items on the PI was evaluated. Any other additional information present on PI was also noted. Each item was analyzed and expressed as percentages. The information on 258 PIs included: Name of ingredients (67%), quantity of ingredients (47.27%), route of administration (86.8%), dosage form (86.8%), indications (18%), dose (18%), contraindications (18%), side effects (9%), shelf life (5.81%), storage conditions (11%), and manufacturers name with contact details (34%). PIs accompanying Ayurveda medicinal products in India are deficient in information required to be furnished by them.

  15. A replication and methodological critique of the study "Evaluating drug trafficking on the Tor Network".

    Science.gov (United States)

    Munksgaard, Rasmus; Demant, Jakob; Branwen, Gwern

    2016-09-01

    The development of cryptomarkets has gained increasing attention from academics, including growing scientific literature on the distribution of illegal goods using cryptomarkets. Dolliver's 2015 article "Evaluating drug trafficking on the Tor Network: Silk Road 2, the Sequel" addresses this theme by evaluating drug trafficking on one of the most well-known cryptomarkets, Silk Road 2.0. The research on cryptomarkets in general-particularly in Dolliver's article-poses a number of new questions for methodologies. This commentary is structured around a replication of Dolliver's original study. The replication study is not based on Dolliver's original dataset, but on a second dataset collected applying the same methodology. We have found that the results produced by Dolliver differ greatly from our replicated study. While a margin of error is to be expected, the inconsistencies we found are too great to attribute to anything other than methodological issues. The analysis and conclusions drawn from studies using these methods are promising and insightful. However, based on the replication of Dolliver's study, we suggest that researchers using these methodologies consider and that datasets be made available for other researchers, and that methodology and dataset metrics (e.g. number of downloaded pages, error logs) are described thoroughly in the context of web-o-metrics and web crawling. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. [Professional practice evaluation of injectable drug preparation and administration in neonatology].

    Science.gov (United States)

    Morin, P; Guillois, B; Gloanec, L; Chatelier, N; Saint-Lorant, G

    2017-09-01

    Adverse drug events are a daily concern in neonatology departments. The aim of this study was to assess the professional practices of preparation and administration of injectable forms of medications in neonatology. A professional practice evaluation with regard to the preparation and administration of various injectable forms of medications in different neonatology units within a given department was conducted by a pharmacy intern based on an assessment grid comprising ten criteria. Following an initial assessment, the results were presented to the care team, which validated the corrective measures put forward by a multiprofessional work group. A second assessment was conducted following the same methodology. Fifty of the department's 76 pediatric nurses were assessed during the first round of the audit and 21 during the second round. Two improvement priorities were identified: taking account of the dead volume of medication in needles and syringe hubs, together with complete identification of syringes used to administer medication. During the second round, these two aspects were improved, progressing from 38% to 100% and from 59% to 89%, respectively. To improve drug administration in neonatology and consequently, to improve patient safety, professional practice evaluation is an essential tool that requires close collaboration between the paramedical team, physicians and pharmacists. Its main value lies in the mobilization of the entire team around the subject in question, hence generating improved understanding and application of corrective measures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Enhancement of the efficiency of magnetic targeting for drug delivery: Development and evaluation of magnet system

    International Nuclear Information System (INIS)

    Cao Quanliang; Han Xiaotao; Li Liang

    2011-01-01

    Deep magnetic capture and clinical application are the current trends for magnetic targeted drug delivery system. More promising and possible strategies are needed to overcome the current limitations and further improve the magnetic targeting technique. Recent advances in the development of targeting magnet system show promise in progressing this technology from the laboratory to the clinic. Starting from well-known basic concepts, current limitations of magnetic targeted drug delivery system are analyzed. Meanwhile, the design concepts and evaluations of some effective improvements in magnet system are discussed and reviewed with reference to (i) reasonable design of magnet system; (ii) control modes of magnet system used to generate dynamical magnetic fields; and (iii) magnetic field driving types. - Research Highlights: → The current limitations of MTDDS for deep capture and clinical application are analyzed. → The development of magnet system shows promise in progressing MTDDS to clinical application. → The design concepts and evaluations of improvements in magnet system are reviewed and discussed. → The key to improve magnet system lies in controllable magnets and different excitations.

  18. Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse.

    Science.gov (United States)

    Hall, E S; Wexelblatt, S L; Greenberg, J M

    2016-10-01

    The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse. The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection. Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (Pdrugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures. Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources.

  19. Inter relationship between some routine semen evaluation parameters in Jersey X local hill cattle crossbred bulls

    Directory of Open Access Journals (Sweden)

    S. Kapoor

    2012-05-01

    Full Text Available The present study was conducted with an objective of establishing a relationship between various routine semen evaluation parameters. Work was conducted at Sperm Station Palampur, Himachal Pradesh, on the semen from five Jersey X local hill cattle crossbred breeding bulls. A total of 40 ejaculates (8 from each bull, were analysed at five different stages of processing namely post dilution, post equilibration, post thaw and after 1 and 2 hours incubation post thaw at 37°C for progressive motility, live dead count, reaction to hypo-osmotic solution, acrosomal integrity and gross morphological abnormalities. The results of the study revealed a highly significant (P<0.01 correlation between the various semen evaluation parameters except for the gross morphological abnormalities where there was a significant (P<0.05 negative correlation between the acrosomal integrity and gross morphological abnormalities.

  20. Scintigraphic method for evaluating reductions in local blood volumes in human extremities

    DEFF Research Database (Denmark)

    Blønd, L; Madsen, Jan Lysgård

    2000-01-01

    in the experiment. Evaluation of one versus two scintigraphic projections, trials for assessment of the reproducibility, a comparison of the scintigraphic method with a water-plethysmographic method and registration of the fractional reduction in blood volume caused by exsanguination as a result of simple elevation......% in the lower limb experiment and 6% in the upper limb experiment. We found a significant relation (r = 0.42, p = 0.018) between the results obtained by the scintigraphic method and the plethysmographic method. In fractions, a mean reduction in blood volume of 0.49+0.14 (2 SD) was found after 1 min of elevation......We introduce a new method for evaluating reductions in local blood volumes in extremities, based on the combined use of autologue injection of 99mTc-radiolabelled erythrocytes and clamping of the limb blood flow by the use of a tourniquet. Twenty-two healthy male volunteers participated...

  1. Reduction in sodium content of local anesthetics for peripheral nerve blocks: a comparative evaluation of saline with 5% dextrose--a randomized controlled double-blind study.

    Science.gov (United States)

    Dhir, Shalini; Tureanu, Luminita; Bouzari, Amir; Masood, Amna; Francispragasam, Mario; Ganapathy, Sugantha

    2012-06-01

    Commercially available local anesthetic drugs when diluted with normal saline have high sodium content. High perineural sodium concentration has been implicated in antagonizing the analgesic effects of local anesthetics by preventing and/or delaying neural blockade. Five percent dextrose is not known to cause any short- or long-term injury when injected around neural tissue. In this study, we prospectively compared and evaluated block characteristics when local anesthetic drug was diluted with these 2 different agents. Patients scheduled for upper limb surgery were randomly assigned to receive axillary brachial plexus block with 0.5% ropivacaine (1% diluted with either 5% dextrose or normal saline). Motor and sensory block were tested every 5 minutes for 30 minutes. Postoperatively, a telephone interview was conducted after 24 hours and 7 days along with surgical follow-up at days 3, 10, and/or 14 to 28 days to document side effects, patient satisfaction, and time for block resolution. Any nerve deficits were followed until resolution. The primary outcome was time to onset of sensory nerve block. Five hundred fifty patients were recruited for this study. The mean time to complete sensory block was 18.3 ± 6.1 minutes in the dextrose group and 22.5 ± 6.4 minutes in the saline group (P dextrose provides earlier onset of axillary brachial plexus block with ropivacaine.

  2. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Louise, E-mail: louise.marks@astrazeneca.com [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Kirk, Sarah [Innovative Medicines, Discovery Sciences, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Valentin, Jean-Pierre [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom)

    2012-09-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt{sub max} and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability.

  3. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    International Nuclear Information System (INIS)

    Marks, Louise; Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew; Kirk, Sarah; Valentin, Jean-Pierre

    2012-01-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt max and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability. ► Haemodynamic

  4. Evaluation of the Prostate Bed for Local Recurrence After Radical Prostatectomy Using Endorectal Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Liauw, Stanley L.; Pitroda, Sean P.; Eggener, Scott E.; Stadler, Walter M.; Pelizzari, Charles A.; Vannier, Michael W.; Oto, Aytek

    2013-01-01

    Purpose: To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study. Methods and Materials: Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP. The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4. Results: Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA ≤0.3 ng/mL (P 3 and was directly associated with PSA (r=0.5, P=.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins (r=0.8, P<.01). Conclusions: Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA. Further study is necessary to determine whether eMRI can

  5. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment.

    Science.gov (United States)

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. The multimodality treatment was feasible, and triple

  6. Non-Destructive Evaluation of Kissing Bonds using Local Defect Resonance (LDR) Spectroscopy: A Simulation Study

    Science.gov (United States)

    Delrue, S.; Tabatabaeipour, M.; Hettler, J.; Van Den Abeele, K.

    With the growing demand from industry to optimize and further develop existing Non-Destructive Testing & Evaluation (NDT&E) techniques or new methods to detect and characterize incipient damage with high sensitivity and increased quality, ample efforts have been devoted to better understand the typical behavior of kissing bonds, such as delaminations and cracks. Recently, it has been shown experimentally that the nonlinear ultrasonic response of kissing bonds could be enhanced by using Local Defect Resonance (LDR) spectroscopy. LDR spectroscopy is an efficient NDT technique that takes advantage of the characteristic fre- quencies of the defect (defect resonances) in order to provide maximum acoustic wave-defect interaction. In fact, for nonlinear methodologies, the ultrasonic excitation of the sample should occur at either multiples or integer ratios of the characteristic defect resonance frequencies, in order to obtain the highest signal-to-noise response in the nonlinear LDR spectroscopy. In this paper, the potential of using LDR spectroscopy for the detection, localization and characterization of kissing bonds is illustrated using a 3D simulation code for elastic wave propagation in materials containing closed but dynamically active cracks or delaminations. Using the model, we are able to define an appropriate method, based on the Scaling Subtraction Method (SSM), to determine the local defect resonance frequencies of a delamination in a composite plate and to illustrate an increase in defect nonlinearity due to LDR. The simulation results will help us to obtain a better understanding of the concept of LDR and to assist in the further design and testing of LDR spectroscopy for the detection, localization and characterization of kissing bonds.

  7. A rural CT scanner: evaluating the effect on local health care

    International Nuclear Information System (INIS)

    Merkens, B.J.; Mowbray, R.D.; Creeden, L.; Engels, P.T.; Rothwell, D.M.; Chan, B.T.B.; Tu, K.

    2006-01-01

    The first small rural hospital in Ontario to propose a computed tomography (CT) scanner was in Walkerton, a town 160 km north of London. The Ontario Ministry of Health approved the proposal as a pilot project to evaluate the effect on local health care of a rural scanner. This evaluation study had 3 parts: a survey of physicians, a survey of patients, and an analysis of population CT scanning rates. The physicians in the area served by the scanner were asked about its impact on their care of their patients in a mailed questionnaire and in semistructured interviews. Scanner outpatients were given a questionnaire in which they rated the importance of its advantages. The analysis of scanning rates--the ratio of number of scans to estimated population--compared rates in the area with other Ontario rates before and after the scanner was introduced. The physicians reported that local CT allowed them to diagnose and treat patients sooner, closer to home, and with greater confidence. On average, 75% of the patients ranked faster and closer access as very important. Scanning rates in the area rose, although they did not match urban rates. The study confirms that the rural scanner changed the area's health care in significant ways and that it helped to narrow the gap between rural and urban service levels. We recommend that CT be expanded to other rural regions. (author)

  8. DRUG EVALUATION AND DECISION MAKING IN CATALONIA: DEVELOPMENT AND VALIDATION OF A METHODOLOGICAL FRAMEWORK BASED ON MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR ORPHAN DRUGS.

    Science.gov (United States)

    Gilabert-Perramon, Antoni; Torrent-Farnell, Josep; Catalan, Arancha; Prat, Alba; Fontanet, Manel; Puig-Peiró, Ruth; Merino-Montero, Sandra; Khoury, Hanane; Goetghebeur, Mireille M; Badia, Xavier

    2017-01-01

    The aim of this study was to adapt and assess the value of a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan drugs in Catalonia (Catalan Health Service). The standard evaluation and decision-making procedures of CatSalut were compared with the EVIDEM methodology and contents. The EVIDEM framework was adapted to the Catalan context, focusing on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with sixteen PASFTAC members. The criteria weighting was done using two different techniques (nonhierarchical and hierarchical). Reliability was assessed by re-test. The EVIDEM framework and methodology was found useful and feasible for Orphan drugs evaluation and decision making in Catalonia. All the criteria considered for the development of the CatSalut Technical Reports and decision making were considered in the framework. Nevertheless, the framework could improve the reporting of some of these criteria (i.e., "unmet needs" or "nonmedical costs"). Some Contextual criteria were removed (i.e., "Mandate and scope of healthcare system", "Environmental impact") or adapted ("population priorities and access") for CatSalut purposes. Independently of the weighting technique considered, the most important evaluation criteria identified for orphan drugs were: "disease severity", "unmet needs" and "comparative effectiveness", while the "size of the population" had the lowest relevance for decision making. Test-retest analysis showed weight consistency among techniques, supporting reliability overtime. MCDA (EVIDEM framework) could be a useful tool to complement the current evaluation methods of CatSalut, contributing to standardization and pragmatism, providing a method to tackle ethical dilemmas and facilitating discussions related to decision making.

  9. Evaluation of the effect of locally administered amitriptyline gel as adjunct to local anesthetics in irreversible pulpitis pain

    Directory of Open Access Journals (Sweden)

    Moghadamnia A

    2009-01-01

    Full Text Available Background: Amitriptyline is one of the most common tricyclic antidepressants, which binds to pain sensory nerve fibers close to the sodium channel; hence, it could interact to some degree with receptors of local anesthetics. This study was designed to assess the additional analgesic effects of 2% Amitriptyline local gel administration in irreversible pulpitis pain of the molars. Materials and Methods: This study was a randomized, double-blind clinical trial that was performed on 56 consented adult patients who did not receive enough analgesia after a lidocaine nerve block for their tooth pulpitis pain. Patients were treated with 0.2 ml of either 2% amitriptyline or placebo, which was directly injected into their mandibular molar pulp chamber after they had received two routine lidocaine injections. Patients were asked to score their pain as a mark on a 10-cm Visual Analogue Scale (VAS at different timepoints: 0 (just before gel administration, 1, 3, 5, 7, and 9 minutes after the treatments. Results: There was a 92.5% decrease in VAS scores of patients 9 minutes after amitriptyline administration compared to Time 0, while in the placebo group this difference was only 13.5%. Further, in the amitriptyline group, the VAS score at all timepoints was statistically different from Time 0 ( P < 0.01. The overall pain reduction and its trend was significantly higher in the amitriptyline group compared with the placebo group ( P < 0.001. Conclusion: Inter-pulp space administration of amitriptyline 2% gel for completing analgesia in irreversible pulpitis pain could be effective and useful as a conjunctive therapy to injections of local anesthetics.

  10. Maximizing Health or Sufficient Capability in Economic Evaluation? A Methodological Experiment of Treatment for Drug Addiction.

    Science.gov (United States)

    Goranitis, Ilias; Coast, Joanna; Day, Ed; Copello, Alex; Freemantle, Nick; Frew, Emma

    2017-07-01

    Conventional practice within the United Kingdom and beyond is to conduct economic evaluations with "health" as evaluative space and "health maximization" as the decision-making rule. However, there is increasing recognition that this evaluative framework may not always be appropriate, and this is particularly the case within public health and social care contexts. This article presents a methodological case study designed to explore the impact of changing the evaluative space within an economic evaluation from health to capability well-being and the decision-making rule from health maximization to the maximization of sufficient capability. Capability well-being is an evaluative space grounded on Amartya Sen's capability approach and assesses well-being based on individuals' ability to do and be the things they value in life. Sufficient capability is an egalitarian approach to decision making that aims to ensure everyone in society achieves a normatively sufficient level of capability well-being. The case study is treatment for drug addiction, and the cost-effectiveness of 2 psychological interventions relative to usual care is assessed using data from a pilot trial. Analyses are undertaken from a health care and a government perspective. For the purpose of the study, quality-adjusted life years (measured using the EQ-5D-5L) and years of full capability equivalent and years of sufficient capability equivalent (both measured using the ICECAP-A [ICEpop CAPability measure for Adults]) are estimated. The study concludes that different evaluative spaces and decision-making rules have the potential to offer opposing treatment recommendations. The implications for policy makers are discussed.

  11. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model -

    Directory of Open Access Journals (Sweden)

    Himanshu R Gupta

    2016-12-01

    Full Text Available Objectives: Advancements in nanotechnology have led to nanoparticle (NP use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio. Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED. For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and

  12. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs: - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model.

    Science.gov (United States)

    Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty; Thakur, Mansee

    2016-12-01

    Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos ( Danio rerio ). Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish

  13. Strategies for the early detection of drug-induced hepatic steatosis in preclinical drug safety evaluation studies

    International Nuclear Information System (INIS)

    Amacher, David E.

    2011-01-01

    Hepatic steatosis is characterized by the accumulation of lipid droplets in the liver. Although relatively benign, simple steatosis can eventually lead to the development of steatohepatitis, a more serious condition characterized by fibrosis, cirrhosis, and eventual liver failure if the underlying cause is not eliminated. According to the 'two hit' theory of steatohepatitis, the initial hit involves fat accumulation in the liver, and a second hit leads to inflammation and subsequent tissue injury. Because some xenobiotics target liver fatty acid metabolism, especially mitochondrial β-oxidation, it is important to avoid potential drug candidates that can contribute to either the initiation of liver steatosis or progression to the more injurious steatohepatitis. The gold standard for the detection of these types of hepatic effects is histopathological examination of liver tissue. In animal studies, these examinations are slow, restricted to a single sampling time, and limited tissue sections. Recent literature suggests that rapid in vitro screening methods can be used early in the drug R and D process to identify compounds with steatotic potential. Further, progress in the identification of potential serum or plasma protein biomarkers for these liver changes may provide additional in vivo tools to the preclinical study toxicologist. This review summarizes recent developments for in vitro screening and in vivo biomarker detection for steatotic drug candidates.

  14. Intrabronchial Microdialysis: Effects of Probe Localization on Tissue Trauma and Drug Penetration into the Pulmonary Epithelial Lining Fluid

    DEFF Research Database (Denmark)

    Rottbøll, Lisa Amanda Holm; Skovgaard, Kerstin; Barington, Kristiane

    2015-01-01

    (PELF). The objective of this study was to investigate the effect of intrabronchial microdialysis on the integrity of the bronchial epithelium. Microdialysis sampling in PELF in proximal (n=4) and distal bronchi (n=4) was performed after intravenous inulin and florfenicol administration in anaesthetized...... pigs. Inulin was used as a marker molecule of permeability of the epithelium, and florfenicol was used as test drug. Bronchial tissue was examined by histopathology (distal and proximal bronchi) and gene expression analysis (RT-qPCR, proximal bronchi) at the termination of the experiment (6.5hr....... Likewise, florfenicol penetration into PELF was unaffected by bronchial histopathology. However, this independency of pathology on drug penetration may not be valid for other antibiotics. We conclude that short-term microdialysis drug quantification can be performed in proximal bronchi without disruption...

  15. Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

    Science.gov (United States)

    Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

    2013-12-01

    Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Development of an Official Guideline for the Economic Evaluation of Drugs/Medical Devices in Japan.

    Science.gov (United States)

    Shiroiwa, Takeru; Fukuda, Takashi; Ikeda, Shunya; Takura, Tomoyuki; Moriwaki, Kensuke

    2017-03-01

    In Japan, cost-effectiveness evaluation was implemented on a trial basis from fiscal year 2016. The results will be applied to the future repricing of drugs and medical devices. On the basis of a request from the Central Social Insurance Medical Council (Chuikyo), our research team drafted the official methodological guideline for trial implementation. Here, we report the process of developing and the contents of the official guideline for cost-effectiveness evaluation. The guideline reflects discussions at the Chuikyo subcommittee (e.g., the role of quality-adjusted life-year) and incorporates our academic perspective. Team members generated research questions for each section of the guideline and discussions on these questions were carried out. A draft guideline was prepared and submitted to the Ministry of Health, Labour and Welfare (MHLW), and then to the subcommittee. The draft guideline was revised on the basis of the discussions at the subcommitte, if appropriate. Although the "public health care payer's perspective" is standard in this guideline, other perspectives can be applied as necessary depending on the objective of analysis. On the basis of the discussions at the subcommittee, quality-adjusted life-year will be used as the basic outcome. A discount rate of 2% per annum for costs and outcomes is recommended. The final guideline was officially approved by the Chuikyo general assembly in February 2016. This is the first officially approved guideline for the economic evaluation of drugs and medical devices in Japan. The guideline is expected to improve the quality and comparability of submitted cost-effectiveness data for decision making. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  17. [An evaluation of a symposium via satellite on alcoholism and drug dependence].

    Science.gov (United States)

    Ríos-Espinosa, E; Martínez-Salgado, H; Ruíz-Tapia, R; Domínguez-Cherit, L

    1993-01-01

    Results of a test given to participants in a symposium on alcoholism and drug abuse are presented. The symposium was broadcast via satellite simultaneously to five cities in Mexico, and included 8 pretaped panels covering topics on alcoholism and drug abuse. The methodology used for broadcasting the symposium allowed the interactive exchange of information between expert lecturers and participants. The quantitative and qualitative evaluation used the pretest-posttest design. Most of the participants were physicians (28.9%) followed by psychologists (25.7%) and social workers (18.1%). The global cognitive change among participants was 6 per cent. Almost 77 per cent of participants had scores between 51 and 70 points (over a possible maximum score of 100) in the pre-evaluation test, and 76.4 per cent had scores between 61 and 80 points in the postevaluation test. Health professionals with 1-3 years of experience had the largest change in scores (9%), followed by those with 3 to 5 years experience (8%). Professionals with 5 to 10 years of experience had a change of 5 per cent. Physicians showed the greatest cognitive change (7%) followed by psychologists and social workers with 5 per cent change. In the qualitative evaluation, 87.6 per cent of participants thought that the educational method used was "Excellent" of "Good". With respect to the satellite transmission, 79.4 per cent of participants thought it was "Excellent" or "Good". It is concluded that this type of educational events are useful in reaching health professionals who otherwise would not have access to specialized and updated information.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Evaluation of local trace element status and 8-Iso-prostaglandin F2α concentrations in patients with Tinea pedis.

    Science.gov (United States)

    Miraloglu, Meral; Kurutas, Ergul Belge; Ozturk, Perihan; Arican, Ozer

    2016-01-01

    Tinea pedis (TP) is an infection of the feet caused by fungi. The infectious diseases caused by dermatophytes are mainly related to the enzymes produced by these fungi. Up to the now, the local 8-iso-prostaglandin F2α (8-iso-PGF2α), concentration as oxidative stress biomarker and trace elements status have not been published in patients with TP. The aim of this study is to evaluate the relationship between oxidative stress and trace elements (Cu, Zn, Se), and to evaluate the ratios of Cu/Zn and Cu/Se in this disorder. Forty-three consecutive patients with a diagnosis of unilateral interdigital TP were enrolled in this study. The samples were obtained by scraping the skin surface. 8-iso-PGF2α concentrations in scraping samples were determined by ELISA. In addition, the levels of Se, Zn and Cu in scraping samples were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction. Oxidative stress was confirmed by the significant elevation in 8-iso-PGF2α concentrations (p iso-PGF2α parameters, but negative correlations between Se-Cu; Se-8-iso-PGF2α parameters in lesional area. Furthermore, the ratios of Cu/Zn and Cu/Se were significantly higher on the lesional area than the non-lesional area (p iso-PGF2α and trace elements in patients with TP (p > 0.05). Our results showed that there is a possible link between oxidative stress (increased 8-iso-PGF2α concentrations) and imbalanced of trace elements status in lesional area of TP patients. The use of antifungal agents together with both Zn and Se drugs could be helpful in the both regression of disease and in shortening the duration of disease.

  19. Field installation versus local integration of photovoltaic systems and their effect on energy evaluation metrics

    International Nuclear Information System (INIS)

    Halasah, Suleiman A.; Pearlmutter, David; Feuermann, Daniel

    2013-01-01

    In this study we employ Life-Cycle Assessment to evaluate the energy-related impacts of photovoltaic systems at different scales of integration, in an arid region with especially high solar irradiation. Based on the electrical output and embodied energy of a selection of fixed and tracking systems and including concentrator photovoltaic (CPV) and varying cell technology, we calculate a number of energy evaluation metrics, including the energy payback time (EPBT), energy return factor (ERF), and life-cycle CO 2 emissions offset per unit aperture and land area. Studying these metrics in the context of a regionally limited setting, it was found that utilizing existing infrastructure such as existing building roofs and shade structures does significantly reduce the embodied energy requirements (by 20–40%) and in turn the EPBT of flat-plate PV systems due to the avoidance of energy-intensive balance of systems (BOS) components like foundations. Still, high-efficiency CPV field installations were found to yield the shortest EPBT, the highest ERF and the largest life-cycle CO 2 offsets—under the condition that land availability is not a limitation. A greater life-cycle energy return and carbon offset per unit land area is yielded by locally-integrated non-concentrating systems, despite their lower efficiency per unit module area. - Highlights: ► We evaluate life-cycle energy impacts of PV systems at different scales. ► We calculate the energy payback time, return factor and CO 2 emissions offset. ► Utilizing existing structures significantly improves metrics of flat-plate PV. ► High-efficiency CPV installations yield best return and offset per aperture area. ► Locally-integrated flat-plate systems yield best return and offset per land area.

  20. Compulsory Project-Level Involvement and the Use of Program-Level Evaluations: Evaluating the Local Systemic Change for Teacher Enhancement Program

    Science.gov (United States)

    Johnson, Kelli; Weiss, Iris R.

    2011-01-01

    In 1995, the National Science Foundation (NSF) contracted with principal investigator Iris Weiss and an evaluation team at Horizon Research, Inc. (HRI) to conduct a national evaluation of the Local Systemic Change for Teacher Enhancement program (LSC). HRI conducted the core evaluation under a $6.25 million contract with NSF. This program…

  1. Evaluation of optical localization in the visible band for ultrasound guidance in radiotherapy using a robotic arm

    NARCIS (Netherlands)

    Camps, S.M.; Costa, M.; Stevens, E.; Sanches, P.G.; Paiva Fonesca, G.; Bellezzo, M.; Verhaegen, F.

    2017-01-01

    In many medical fields, spatial localization of devices is of paramount importance to e.g. deliver treatments correctly or to perform accurate diagnostic evaluations. Among the different technologies available, optical localization in the visible band of the spectrum offers many advantages: minimum

  2. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    Directory of Open Access Journals (Sweden)

    Bonanno L

    2016-06-01

    Full Text Available Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs. No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1, paclitaxel (200 mg/m2, d1, and gemcitabine (1,000 mg/m2 d1, 8 for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS and overall survival (OS were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system. A total of 36 (62% patients achieved partial response (PR, and six (10% progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62% cases. After chemotherapy, 37 (64% patients underwent surgery

  3. Evaluation of Electronic Healthcare Databases for Post-Marketing Drug Safety Surveillance and Pharmacoepidemiology in China.

    Science.gov (United States)

    Yang, Yu; Zhou, Xiaofeng; Gao, Shuangqing; Lin, Hongbo; Xie, Yanming; Feng, Yuji; Huang, Kui; Zhan, Siyan

    2018-01-01

    Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. Three major types of EHDs in China (i.e., a regional community-based database, a national claims database, and an electronic medical records [EMR] database) were selected for evaluation. Forty core variables were derived based on the US Mini-Sentinel (MS) Common Data Model (CDM) as well as the data features in China that would be desirable to support drug safety surveillance. An email survey of these core variables and eight general questions as well as follow-up inquiries on additional variables was conducted. These 40 core variables across the three EHDs and all variables in each EHD along with those in the US MS CDM and Observational Medical Outcomes Partnership (OMOP) CDM were compared for availability and labeled based on specific standards. All of the EHDs' custodians confirmed their willingness to share their databases with academic institutions after appropriate approval was obtained. The regional community-based database contained 1.19 million people in 2015 with 85% of core variables. Resampled annually nationwide, the national claims database included 5.4 million people in 2014 with 55% of core variables, and the EMR database included 3 million inpatients from 60 hospitals in 2015 with 80% of core variables. Compared with MS CDM or OMOP CDM, the proportion of variables across the three EHDs available or able to be transformed/derived from the original sources are 24-83% or 45-73%, respectively. These EHDs provide potential value to post-marketing drug safety surveillance and pharmacoepidemiology in China. Future research is warranted to assess the quality and completeness of these EHDs or additional data sources in China.

  4. Pseudomonas aeruginosa: evaluation of pathogen burden and drug-resistance trends in a tertiary care hospital

    International Nuclear Information System (INIS)

    Saeed, M.; Hussain, S.; Ahmad, A.

    2018-01-01

    To evaluate the pathogen burden and antibiotic-resistance trends of Pseudomonas aeruginosa among hospitalised patients at a tertiary care hospital. Study Design:Retrospective, hospital record-based, cross-sectional study. Place and Duration of Study:Microbiology Laboratory, Allama Iqbal Medical College/Jinnah Hospital, Lahore, from January 2014 to December 2016. Methodology:A total of 5,960 samples were collected from clinically suspected cases of bacterial infections, admitted to the hospital. Microbial identification and antibiotic susceptibility pattern were carried out and analysed. Results:Out of a total of 5,960 samples, Pseudomonas aeruginosawas isolated from 1,268 (21.2%) specimens. Department-wise isolation rate was n=600 (42.9%), n=268 (15.4%), n=201 (12.6%), and n=199 (16.0%) from intensive care unit (ICU), surgical units, medical units, and Gynae wards, respectively (p<0.0001). Sample-wise isolation rate was, wound swabs n=448 (35%), urine n=356 (28%), sputum n=187 (14 %), tracheal aspirate n=127 (10%), blood n=99 (7%), and broncho-alveolar lavage n=51 (4%) (p<0.0001). Drug-resistance pattern showed low rates for carbapenems (meropenem n=440 (35%), Imipenem n=436 (34%) and beta-lactam + beta-lactamase inhibitor combination (piperacillin+ tazobactam n=437 (34%) while alarming rates were observed for cephalosporins (ceftazidime n=716 (56%), fluoroquinolones (ciprofloxacin n=690 (54%), cefoperazone+sulbactam n=685 (54%), aminoglycosides (gentamicin, n=669 (53%), amikacin n=608 (48%), and monobactams (aztreonam n=666 (52%). Decreasing trend was observed only for amikacin 63% to 37%, aztreonam showed similar pattern throughout, while there was an increasing trend of drug resistance in all groups of antibiotics. Conclusion:Emerging drug-resistant strains of Pseudomonas aeruginosaare probably linked to the injudicious use of antibiotics, leading to ineffective empirical therapy. Therefore, we suggest that culture and antimicrobial susceptibility testing should

  5. Cost evaluation of therapeutic drug monitoring of gentamicin at a teaching hospital in Malaysia

    Directory of Open Access Journals (Sweden)

    Ibrahim MI

    2014-03-01

    Full Text Available Background: Therapeutic drug monitoring (TDM makes use of serum drug concentrations as an adjunct to decision-making. Preliminary data in our hospital showed that approximately one-fifth of all drugs monitored by TDM service were gentamicin. Objective: In this study, we evaluated the costs associated with providing the service in patients with bronchopneumonia and treated with gentamicin. Methods: We retrospectively collected data from medical records of patients admitted to the Hospital Universiti Sains Malaysia over a 5-year period. These patients were diagnosed with bronchopneumonia and were on gentamicin as part of their treatment. Five hospitalisation costs were calculated; (i cost of laboratory and clinical investigations, (ii cost associated with each gentamicin dose, (iii fixed and operating costs of TDM service, (iv cost of providing medical care, and (v cost of hospital stay during gentamicin treatment. Results: There were 1920 patients admitted with bronchopneumonia of which 67 (3.5% had TDM service for gentamicin. Seventy-three percent (49/67 patients were eligible for final analysis. The duration of gentamicin therapy ranged from 3 to 15 days. The cost of providing one gentamicin assay was MYR25, and the average cost of TDM service for each patient was MYR104. The average total hospitalisation cost during gentamicin treatment for each patient was MYR442 (1EUR approx. MYR4.02. Conclusion: Based on the hospital perspective, in patients with bronchopneumonia and treated with gentamicin, the provision of TDM service contributes to less than 25% of the total cost of hospitalization.

  6. [Safe injection rooms and police crackdowns in areas with heavy drug dealing. Evaluation by counting discarded syringes collected from the public space].

    Science.gov (United States)

    Vecino, Carmen; Villalbí, Joan R; Guitart, Anna; Espelt, Albert; Bartroli, Montserrat; Castellano, Yolanda; Brugal, M Teresa

    2013-01-01

    The evolution of drug injection in public places is analysed using as indicator the number of syringes collected from public spaces, evaluating as well the influence of public health harm reduction interventions and of police actions, with a before and after quasi experimental study. Monthly syringe counts on the semester before and after each intervention were compared both in the involved district and in the city as a whole, using the U and z tests with a 95% confidence level. The average number of collected syringes drops from 13.132 in 2004 to 3.190 in 2012. Comparing indicators before and after health and police interventions, the opening of a facility with a supervised drug consumption room in the inner city was associated with a huge reduction in the number of abandoned syringes in the city, while its number did not rise in the district where the facility was located. The subsequent opening of another drug consumption room did not have a significant impact in collected syringes in the area. Some police interventions in 2005-2006 and 2011 had a significant impact in the indicators of the involved districts, while others did not. Harm reduction programs might have a favourable impact on drug injection in public spaces and related syringe presence. Some police interventions appear to have an impact while others do not or just have a modest local and temporary effect.

  7. Evaluation of transporters in drug development: Current status and contemporary issues.

    Science.gov (United States)

    Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

    2017-07-01

    Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

  8. Needle-less local anesthesia: clinical evaluation of the effectiveness of the jet anesthesia Injex in local anesthesia in dentistry.

    Science.gov (United States)

    Dabarakis, Nikolaos N; Alexander, Veis; Tsirlis, Anastasios T; Parissis, Nikolaos A; Nikolaos, Maroufidis

    2007-01-01

    To clinically evaluate the jet injection Injex (Rösch AG Medizintechnik) using 2 different anesthetic solutions, and to compare the jet injection and the standard needle injection techniques. Of the 32 patients in the study, 10 received mepivacaine 3% anesthetic solution by means of the jet injection technique, while the remaining 22 patients received lidocaine 2% with epinephrine 1:80,000 by the same method. The 14 patients in whom pulp anesthesia was achieved were selected for an additional evaluation of the pulp reaction using standard needle injection anesthesia. The differences between the 2 compounds with Injex were statistically evaluated by means of independent-samples t test analysis. The differences between subgroups receiving both jet injection and needle injection anesthesia were evaluated by means of paired t test analysis. The administration of mepivacaine 3% using Injex did not achieve pulp anesthesia in any of the 10 patients, although the soft tissue anesthesia was successful. The administration of lidocaine with epinephrine using Injex resulted in pulp anesthesia in only 14 patients; soft tissue anesthesia was observed in all patients of this group. There was no statistically significant difference between Injex and the needle injection technique in onset of anesthesia. However, the duration of anesthesia was significantly longer for the needle infiltration group than for the Injex injection group. The anesthetic solution should be combined with a vasoconstriction agent when the Injex technique is implemented.

  9. Evaluation of local stress and local hydrogen concentration at grain boundary using three-dimensional polycrystalline model

    International Nuclear Information System (INIS)

    Ebihara, Ken-ichi; Itakura, Mitsuhiro; Yamaguchi, Masatake; Kaburaki, Hideo; Suzudo, Tomoaki

    2010-01-01

    The decohesion model in which hydrogen segregating at grain boundaries reduces cohesive energy is considered to explain hydrogen embrittlement. Although there are several experimental and theoretical supports of this model, its total process is still unclear. In order to understand hydrogen embrittlement in terms of the decohesion model, therefore, it is necessary to evaluate stress and hydrogen concentration at grain boundaries under experimental conditions and to verify the grain boundary decohesion process. Under this consideration, we evaluated the stress and the hydrogen concentration at grain boundaries in the three-dimensional polycrystalline model which was generated by the random Voronoi tessellation. The crystallographic anisotropy was given to each grain. As the boundary conditions of the calculations, data extracted from the results calculated in the notched round-bar specimen model under the tensile test condition in which fracture of the steel specimen is observed was given to the polycrystalline model. As a result, it was found that the evaluated stress does not reach the fracture stress which was estimated under the condition of the evaluated hydrogen concentration by first principles calculations. Therefore, it was considered that the initiation of grain boundary fracture needs other factors except the stress concentration due to the crystallographic anisotropy. (author)

  10. Cationic Gelatin Nanoparticles for Drug Delivery to the Ocular Surface: In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Ching-Li Tseng

    2013-01-01

    Full Text Available To develop an effective ocular drug delivery carrier, we prepared two different charged gelatin nanoparticles (GPs and evaluated particle size, surface charge, and morphology. The in vitro biocompatibility of GPs was assessed using human corneal epithelium (HCE cells and in vivo safety by administering them as eye drops to New Zealand rabbits. The GPs prepared using type A gelatin were positively charged (GP(+, +33 mV; size, 180.6±45.7 nm. Water-soluble tetrazolium salt (WST-1 assay showed that both GPs were nontoxic to HCE cells. The fluorescence intensity of HCE cells cultured with cationic GPs conjugated with a fluorescent dye was higher than that of the anionic GP-treated HCE cells. In vivo examination showed no serious irritation to the rabbit eyes. Furthermore, corneal thickness and ocular pressure in the eyes of the treated rabbits were similar to those in the eyes of normal rabbits. Microscopic examination of corneal cryosections showed widely distributed fluorescent nanocarriers, from the anterior to the posterior part of the cornea of the GP(+ group, and higher fluorescence intensity in the GP(+ group was also observed. In conclusion, GPs as cationic colloidal carriers were efficiently adsorbed on the negatively charged cornea without irritating the eyes of the rabbits and can be retained in the cornea for a longer time. Thus, GPs(+ have a great potential as vehicles for ocular drug delivery.

  11. Relationship between xerostomia and psychotropic drugs in patients with schizophrenia: evaluation using an oral moisture meter.

    Science.gov (United States)

    Okamoto, A; Miyachi, H; Tanaka, K; Chikazu, D; Miyaoka, H

    2016-12-01

    Patients with schizophrenia are most commonly treated with antipsychotic medications, often with the addition of anxiolytics. This study used an oral moisture meter to evaluate xerostomia in patients with schizophrenia taking typical and atypical antipsychotics, anxiolytics and non-psychotropic medications. Patients diagnosed with schizophrenia according to ICD-10 criteria in the Department of Psychiatry, Kitasato University East, and affiliated hospitals were studied. All patients were on psychotropic medications. Patients with diseases associated with xerostomia, such as Sjögren's syndrome I, were excluded. A total of 127 patients were enrolled. Mean oral moisture was 27·81 ± 2·27% (normal, ≥30·0%). A significant association was observed between objective oral moisture and the subjective sense of dry mouth. Multivariate analysis revealed a negative correlation between the number of antipsychotics and, especially, anxiolytics, and the degree of oral moisture. Drug dosages themselves were not significantly correlated with dry mouth. These findings suggest that objective oral moisture measurements show decreased moisture in patients on these medications and that the degree of moisture shows a greater negative correlation with the number, as opposed to the dosages, of psychotropic drugs administered. When patients with schizophrenia visit a dental clinic, it is important for the dentist to accurately assess the degree of oral moisture and to determine the medications being taken. Based on these findings of the association of polypharmacy with xerostomia, dentists are encouraged to inform the psychiatrist of the need to actively manage patients' xerostomia. © 2016 John Wiley & Sons Ltd.

  12. Toxicity Evaluation of Through Fish Bioassay Raw Bulk Drug Industry Wastewater After Electrochemical Treatment

    Directory of Open Access Journals (Sweden)

    S Satyanarayan

    2011-10-01

    Full Text Available Considering the high pollution potential that the synthetic Bulk Drug industry Wastewater (BDW possesses due to the presence of variety of refractory organics, toxicity evaluation is of prime importance in assessing the efficiency of the applied wastewater treatment system and in establishing the discharge standards. Therefore, in this study the toxic effects of high strength bulk drug industry wastewater before and after electrochemical treatment on common fish Lebistes reticulatus-(peter were studied under laboratory conditions. Results indicated that wastewater being very strong in terms of color, COD and BOD is found to be very toxic to the studied fish. The LC50 values for raw wastewater and after electrochemical treatment with carbon and aluminium electrodes for 24, 48, 72 and 96 hours ranged between, 2.5-3.6%, 6.8-8.0%, 5.0-5.8% respectively. Carbon electrode showed marginally better removals for toxicity than aluminium electrode. It was evident from the studies that electrochemical treatment reduces toxicity in proportion to the removal efficiency shown by both the electrodes. The reduction in toxicity after treatment indicates the intermediates generated are not toxic than the parent compounds. Furthermore, as the electrochemical treatment did not result in achieving disposal standards it could be used only as a pre-treatment and the wastewater needs further secondary treatment before final disposal.

  13. Pharmacokinetic drug evaluation of pazopanib for the treatment of uterine leiomyosarcomas.

    Science.gov (United States)

    Ferrero, Simone; Leone Roberti Maggiore, Umberto; Aiello, Nicoletta; Barra, Fabio; Ditto, Antonino; Bogani, Giorgio; Raspagliesi, Francesco; Lorusso, Domenica

    2017-08-01

    Uterine leiomyosarcomas (ULMS) represent 1.3% of all uterine malignant tumors. Surgery is the curative treatment for patients with early stage disease. In case of advanced, persistent or recurrent tumor, chemotherapy represents the standard of care, but these patients have a poor prognosis. As the results with available therapies are far from being satisfactory, research is focusing on identification of new compounds. In 2012 the Food and Drug Administration (FDA) licensed pazopanib for the treatment of advanced soft-tissue sarcomas failing previous chemotherapy. Areas covered: The aim of this article is to review the literature on the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of the tyrosine kinase inhibitor (TKI), pazopanib in the treatment of ULMS. Expert opinion: The discovery of some relevant signalling pathways in LMS cells led to the development of new targeted drugs with promising results in the management of these tumors. Pazopanib is a multi-target second-generation TKI with activity against growth factors involved in angiogenesis. It has shown promising results both in terms of efficacy and safety, as shown in the EORTC 62043 Study and the PALETTE trial. Further studies are awaited to evaluate its efficacy in uterine leiomyosarcomas.

  14. Xenon-133 determination of muscle blood flow: Use in evaluating cardioactive drugs

    International Nuclear Information System (INIS)

    Wexler, J.P.; Davis, L.; Mancini, D.; Chadwick, B.; Le Jemtel, T.

    1985-01-01

    Cardioactive drugs may effect both the central and peripheral circulatory systems. The effects on the central and peripheral circulatory systems of chronic Captorpril therapy in 7 pts with severe congestive heart failure (CHF) were evaluated simultaneously. Skeletal muscle blood flow (SMBF) determined using 133-Xe washout and a Cd/Te detector, oxygen consumption (VO/sub 2/), and radial artery and femoral vein O/sub 2/ concentration difference (A-V) were determined at rest and peak upright bicycle exercise before (BT) and after (AT) 6-12 weeks of Captopril therapy. In CI pts there was a significant increase in VO/sub 2/ and SMBF AT vs BT. In contrast, in CNC pts there was no change in VO/sub 2/ and a significant decrease in SMBF AT vs BT. In pts with severe CHF who are CI, there is an apparent fall in peripheral vascular resistance (PVR). In contrast, in CNC pts there is an increase in PVR. This study demonstrates that SMBF determines using 133-Xe is an important method for determining the effects of cardioactive drugs

  15. Evaluating an approach to improving the adoption rate of wireless drug library updates for smart pumps.

    Science.gov (United States)

    Poppe, Lindsey B; Eckel, Stephen F

    2011-01-15

    An academic medical center's approach to improving the adoption rate of wireless drug library updates for smart pumps was evaluated. A multidisciplinary team composed of pharmacy, nursing, medical engineering, materials management, and patient equipment personnel at an academic medical center collaborated to update the drug libraries of more than 1800 smart pumps via a wireless control system. Two pilot tests were completed to identify and resolve issues before the live wireless update was attempted. The second pilot test, a passive approach, produced an adoption rate of 42% of 1804 pumps at the end of one week and a rate of 56% on day 10. The goal of 80% was not achieved until day 22. The change to an active multidisciplinary process three months later produced an adoption rate of 80% for 1869 pumps on day 10, resulting in a 45.4% increase in the adoption rate between the two trials on day 10 (p libraries reduced the amount of time required to reach a goal adoption rate of 80%.

  16. Feasibility evaluation of 3 automated cellular drug screening assays on a robotic workstation.

    Science.gov (United States)

    Soikkeli, Anne; Sempio, Cristina; Kaukonen, Ann Marie; Urtti, Arto; Hirvonen, Jouni; Yliperttula, Marjo

    2010-01-01

    This study presents the implementation and optimization of 3 cell-based assays on a TECAN Genesis workstation-the Caspase-Glo 3/7 and sulforhodamine B (SRB) screening assays and the mechanistic Caco-2 permeability protocol-and evaluates their feasibility for automation. During implementation, the dispensing speed to add drug solutions and fixative trichloroacetic acid and the aspiration speed to remove the supernatant immediately after fixation were optimized. Decontamination steps for cleaning the tips and pipetting tubing were also added. The automated Caspase-Glo 3/7 screen was successfully optimized with Caco-2 cells (Z' 0.7, signal-to-base ratio [S/B] 1.7) but not with DU-145 cells. In contrast, the automated SRB screen was successfully optimized with the DU-145 cells (Z' 0.8, S/B 2.4) but not with the Caco-2 cells (Z' -0.8, S/B 1.4). The automated bidirectional Caco-2 permeability experiments separated successfully low- and high-permeability compounds (Z' 0.8, S/B 84.2) and passive drug permeation from efflux-mediated transport (Z' 0.5, S/B 8.6). Of the assays, the homogeneous Caspase-Glo 3/7 assay benefits the most from automation, but also the heterogeneous SRB assay and Caco-2 permeability experiments gain advantages from automation.

  17. Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

    Science.gov (United States)

    Dube, T S; Ranpise, N S; Ranade, A N

    2014-01-01

    The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

  18. PLGA nano/microparticles loaded with cresyl violet as a tracer for drug delivery: Characterization and in-situ hyperspectral fluorescence and 2-photon localization

    Energy Technology Data Exchange (ETDEWEB)

    Lunardi, Claure N., E-mail: clunardi@unb.br [Laboratory of Photochemistry and Nanobiotechnology, University of Brasília, Brasília (Brazil); Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY (United States); Gomes, Anderson J. [Laboratory of Photochemistry and Nanobiotechnology, University of Brasília, Brasília (Brazil); Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY (United States); Palepu, Sandeep; Galwaduge, P. Thilanka; Hillman, Elizabeth M.C. [Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY (United States)

    2017-01-01

    Here we present the production, characterization and in-vivo assessment of cresyl violet-loaded biodegradable PLGA nano/microparticles (CV-NP and CV-MP). We demonstrate that the beneficial spectral characteristics of cresyl violet make it suitable as a tracer for particle-based drug delivery using both hyperspectral wide field and two-photon excited fluorescence microscopy. Particles were prepared using a cosolvent method, after which the physicochemical properties such as morphology, particle size, drug entrapment efficiency, drug loading and in vitro drug release behavior were measured in addition to spectroscopic properties, such as absorption, fluorescence and infrared spectra. The particles were then tested in an in vivo mouse model to assess their biodistribution characteristics. The location and integrity of particles after injection was determined using both hyperspectral fluorescence and two-photon microscopy within intact organs in situ. Our results show that cresyl violet is efficiently entrapped into PLGA particles, and that the particles are spherical in shape, ranging from 300 to 5070 nm in diameter. Particle biodistribution in the mouse was found to depend on particle size, as expected. Cresyl violet is shown to be an ideal tracer to assess the properties PLGA particle-based drug delivery in combination with our novel multi-scale optical imaging techniques for in-situ particle localization. - Highlights: • Cresyl violet entrapment into polymeric particles • Cresyl violet suitable as a tracer for particle-based drug delivery • Hyperspectral analysis of polymer nano/microparticles • Two-photon microscopy of polymeric nano/microparticles.

  19. Evaluation of local strain in Si using UV-Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ogura, Atsushi [School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571 (Japan)], E-mail: a_ogura@isc.meiji.ac.jp; Kosemura, Daisuke; Takei, Munehisa [School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571 (Japan); Uchida, Hidetsugu; Hattori, Nobuyoshi [Semiconductor Technology Academic Research Center, 3-17-2 Shinyokohama, Kouhoku-ku, Yokohama 220-0033 (Japan); Yoshimaru, Masaki [Semiconductor Business Group, Sony Corporation, Atsugi Tec., 4-14-1 Asahi-cho, Atsugi-shi, Kanagawa 243-0014 (Japan); Mayuzumi, Satoru [School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571 (Japan); Semiconductor Business Group, Sony Corporation, Atsugi Tec., 4-14-1 Asahi-cho, Atsugi-shi, Kanagawa 243-0014 (Japan); Wakabayashi, Hitoshi [Semiconductor Business Group, Sony Corporation, Atsugi Tec., 4-14-1 Asahi-cho, Atsugi-shi, Kanagawa 243-0014 (Japan)

    2009-03-15

    'Strained-Si', in which intentional strain is introduced in Si crystal to improve carrier mobility by using a modulated band structure, is recognized as one of the most important technologies in post-scaling-generation LSIs. Strain-evaluation technology to probe strain in shallow surfaces that correspond to the channels of MOSFETs is crucial to achieving strained-Si technology. In this paper, we introduce the results we obtained by evaluating strain with the new UV-Raman spectroscopy we developed. Quasi-line shape illumination enabled Raman measurements with 200-nm intervals on the sample. The local-strain mechanism caused by SiN stressors covering a MOSFET was clarified by measuring one-dimensional strain profiles induced by patterned SiN film on Si. We also demonstrated that the induced strain was proportional to the inner stresses of SiN film and that it is more effective to introduce strain in SOI substrates than in bulk substrates. In the evaluation of a actual device fabricated by using the gate-last process in which strain was significantly enhanced after the dummy gate was removed, the size effect, i.e., an increase in induced strain with a decrease in gate length, was confirmed through one-dimensional strain-profile measurements with various gate lengths.

  20. Evaluation of local strain in Si using UV-Raman spectroscopy

    International Nuclear Information System (INIS)

    Ogura, Atsushi; Kosemura, Daisuke; Takei, Munehisa; Uchida, Hidetsugu; Hattori, Nobuyoshi; Yoshimaru, Masaki; Mayuzumi, Satoru; Wakabayashi, Hitoshi

    2009-01-01

    'Strained-Si', in which intentional strain is introduced in Si crystal to improve carrier mobility by using a modulated band structure, is recognized as one of the most important technologies in post-scaling-generation LSIs. Strain-evaluation technology to probe strain in shallow surfaces that correspond to the channels of MOSFETs is crucial to achieving strained-Si technology. In this paper, we introduce the results we obtained by evaluating strain with the new UV-Raman spectroscopy we developed. Quasi-line shape illumination enabled Raman measurements with 200-nm intervals on the sample. The local-strain mechanism caused by SiN stressors covering a MOSFET was clarified by measuring one-dimensional strain profiles induced by patterned SiN film on Si. We also demonstrated that the induced strain was proportional to the inner stresses of SiN film and that it is more effective to introduce strain in SOI substrates than in bulk substrates. In the evaluation of a actual device fabricated by using the gate-last process in which strain was significantly enhanced after the dummy gate was removed, the size effect, i.e., an increase in induced strain with a decrease in gate length, was confirmed through one-dimensional strain-profile measurements with various gate lengths.

  1. Performance evaluation of enzyme immunoassay for voriconazole therapeutic drug monitoring with automated clinical chemistry analyzers.

    Science.gov (United States)

    Jeon, Yongbum; Han, Minje; Han, Eun Young; Lee, Kyunghoon; Song, Junghan; Song, Sang Hoon

    2017-08-01

    Voriconazole is a triazole antifungal developed for the treatment of fungal infectious disease, and the clinical utility of its therapeutic drug monitoring has been evaluated. Recently, a new assay for analyzing the serum voriconazole concentration with an automated clinical chemistry analyzer was developed. We evaluated the performance of the new assay based on standardized protocols. The analytical performance of the assay was evaluated according to its precision, trueness by recovery, limit of quantitation, linearity, and correlation with results from liquid chromatography-tandem mass spectrometry (LC-MS/MS). The evaluation was performed with the same protocol on two different routine chemistry analyzers. All evaluations were performed according to CLSI Guidelines EP15, EP17, EP6, and EP9 [1-4]. Coefficients of variation for within-run and between-day imprecision were 3.2-5.1% and 1.5-3.0%, respectively, on the two different analyzers for pooled serum samples. The recovery rates were in the range of 95.4-102.2%. The limit of blank was 0.0049 μg/mL, and the limit of detection of the samples was 0.0266-0.0376 μg/mL. The percent recovery at three LoQ levels were 67.9-74.6% for 0.50 μg/mL, 75.5-80.2% for 0.60 μg/mL, and 89.9-96.6% for 0.70 μg/mL. A linear relationship was demonstrated between 0.5 μg/mL and 16.0 μg/mL ( R 2 =0.9995-0.9998). The assay correlated well with LC-MS/MS results ( R 2 =0.9739-0.9828). The assay showed acceptable precision, trueness, linearity, and limit of quantification, and correlated well with LC-MS/MS. Therefore, its analytical performance is satisfactory for monitoring the drug concentration of voriconazole.

  2. Synthesis and evaluation of amphiphilic peptides as nanostructures and drug delivery tools

    Science.gov (United States)

    Sayeh, Naser Ali

    us to explore requirements for generating peptides with optimized drug encapsulation and to establish correlations between the structure of peptides with their drug entrapment properties. Thus, the general objective of this dissertation was to design and evaluate additional cyclic or amphiphilic peptides as nanostructures, compare their efficiency in delivery of small molecules with the previously reported cyclic peptides containing tryptophan and arginine residues. This dissertation consists of three chapters. Chapter 1. MANUSCRIPT (published in Current Organic Chemistry 2014). The objective of this work was to design amphiphilic linear and cyclic peptides containing hydrophobic tryptophan W residues that were linked through a triazole ring to positively charged arginine R and lysine (K) residues. The peptides were synthesized through click chemistry between hydrophobic peptides containing alkyne and positively charged peptides containing azide groups. Characterization of their structures like solubility, CD, TEM, cytotoxicity were investigated. The conjugates were showed minimal cytotoxicity at two cell lines. The secondary structures of both peptides were similar to a distorted α-helix as shown by CD spectroscopy. TEM imaging also showed that linear-linear (WG(triazole-KR-NH2))3 and cyclic-linear [WG(triazole-KR-NH2)]3 peptides formed nano-sized structures. Chapter 2. MANUSCRIPT I (Submitted to Journal of Molecular Modeling). In this work, we investigated the structural and dynamical aspects of cyclic-linear peptide ([WG(triazole-KR-NH2)] 3 and linear-linear peptide (WG(triazole-KR-NH2))3) formed nanostructures compared to a drug delivery system with [WR]4. While [WR]4 was found to be an efficient molecular transporter for small molecule drugs, such as lamivudine and dasatinib, cyclic-linear peptide ([WG(triazole-KR-NH2)]3 was inefficient. Molecular modeling was used to explain the differential behavior of these peptides. We showed how the morphology of these

  3. EGFR-targeted anti-cancer drugs in radiotherapy: Preclinical evaluation of mechanisms

    International Nuclear Information System (INIS)

    Baumann, Michael; Krause, Mechthild; Dikomey, Ekkehard; Dittmann, Klaus; Doerr, Wolfgang; Kasten-Pisula, Ulla; Rodemann, H. Peter

    2007-01-01

    Preclinical and clinical results indicate that the EGFR can mediate radioresistance in different solid human tumours. Combination of radiotherapy and EGFR inhibitors can improve local tumour control compared to irradiation alone and has been introduced into clinical radiotherapy practice. So far several mechanisms have been identified in preclinical studies to contribute to improved local tumour control after radiation combined with EGFR inhibitors. These include direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization through modified signal transduction, inhibition of repair of DNA damage, reduced repopulation and improved reoxygenation during fractionated radiotherapy. Effects and mechanisms may differ for different classes of EGFR inhibitors, for different tumours and for normal tissues. The mechanisms underlying this heterogeneity are currently poorly understood, and predictive assays are not available yet. Importantly, mechanisms and predictors for the combined effects of radiation with EGFR inhibitors appear to be considerably different to those for application of EGFR inhibitors alone or in combination with chemotherapy. Therefore to further evaluate the efficacy and mechanisms of EGFR-inhibition in combined treatments, radiotherapy-specific preclinical research strategies, which include in vivo experiments using local tumour control as an endpoint, as well as animal studies on normal tissue toxicity are needed

  4. Economic Evaluation of the Juvenile Drug Court/Reclaiming Futures (JDC/RF) Model.

    Science.gov (United States)

    McCollister, Kathryn; Baumer, Pamela; Davis, Monica; Greene, Alison; Stevens, Sally; Dennis, Michael

    2018-07-01

    Juvenile drug court (JDC) programs are an increasingly popular option for rehabilitating juvenile offenders with substance problems, but research has found inconsistent evidence regarding their effectiveness and economic impact. While assessing client outcomes such as reduced substance use and delinquency is necessary to gauge program effectiveness, a more comprehensive understanding of program success and sustainability can be attained by examining program costs and economic benefits. As part of the National Cross-Site Evaluation of JDC and Reclaiming Futures (RF), an economic analysis of five JDC/RF programs was conducted from a multisystem and multiagency perspective. The study highlights the direct and indirect costs of JDC/RF and the savings generated from reduced health problems, illegal activity, and missed school days. Results include the average (per participant) cost of JDC/RF, the total economic benefits per JDC/RF participant, and the net savings of JDC/RF relative to standard JDC.

  5. Evaluating a policing strategy intended to disrupt an illicit street-level drug market.

    Science.gov (United States)

    Corsaro, Nicholas; Brunson, Rod K; McGarrell, Edmund F

    2010-12-01

    The authors examined a strategic policing initiative that was implemented in a high crime Nashville, Tennessee neighborhood by utilizing a mixed-methodological evaluation approach in order to provide (a) a descriptive process assessment of program fidelity; (b) an interrupted time-series analysis relying upon generalized linear models; (c) in-depth resident interviews. Results revealed that the initiative corresponded with a statistically significant reduction in drug and narcotics incidents as well as perceived changes in neighborhood disorder within the target community. There was less-clear evidence, however, of a significant impact on other outcomes examined. The implications that an intensive crime prevention strategy corresponded with a reduction in specific forms of neighborhood crime illustrates the complex considerations that law enforcement officials face when deciding to implement this type of crime prevention initiative.

  6. Exchange Sex Among Persons Who Inject Drugs in the New York Metropolitan Area: The Importance of Local Context, Gender and Sexual Identity.

    Science.gov (United States)

    Walters, Suzan M; Rivera, Alexis V; Reilly, Kathleen H; Anderson, Bridget J; Bolden, Barbara; Wogayehu, Afework; Neaigus, Alan; Braunstein, Sarah

    2018-02-21

    Exchanging sex for money or drugs is known to increase risk for HIV among persons who inject drugs (PWID). To better understand determinants of exchange sex among PWID we examined factors associated with exchange sex in the New York metropolitan area-defined as New York City (NYC), NY; Newark, NJ; and Long Island, NY-using data from the 2012 National HIV Behavioral Surveillance system cycle on injection drug use. Of the 1160 PWID in this analysis, 24% reported exchange sex, with differences in gender and sexual identity by location. In multivariable analysis gay/bisexual men, heterosexual women, and lesbian, gay, or bisexual (LGB) women were more likely to exchange sex compared to heterosexual men. Exchange sex was also associated with race/ethnicity, homelessness, incarceration, location, and non-injection crack and cocaine use. We find that heterosexual women and LGB women who injected drugs residing in Newark were more likely to report exchange sex compared to NYC. This study highlights how local conditions impact exchange sex.

  7. Evaluating mental workload of two-dimensional and three-dimensional visualization for anatomical structure localization.

    Science.gov (United States)

    Foo, Jung-Leng; Martinez-Escobar, Marisol; Juhnke, Bethany; Cassidy, Keely; Hisley, Kenneth; Lobe, Thom; Winer, Eliot

    2013-01-01

    Visualization of medical data in three-dimensional (3D) or two-dimensional (2D) views is a complex area of research. In many fields 3D views are used to understand the shape of an object, and 2D views are used to understand spatial relationships. It is unclear how 2D/3D views play a role in the medical field. Using 3D views can potentially decrease the learning curve experienced with traditional 2D views by providing a whole representation of the patient's anatomy. However, there are challenges with 3D views compared with 2D. This current study expands on a previous study to evaluate the mental workload associated with both 2D and 3D views. Twenty-five first-year medical students were asked to localize three anatomical structures--gallbladder, celiac trunk, and superior mesenteric artery--in either 2D or 3D environments. Accuracy and time were taken as the objective measures for mental workload. The NASA Task Load Index (NASA-TLX) was used as a subjective measure for mental workload. Results showed that participants viewing in 3D had higher localization accuracy and a lower subjective measure of mental workload, specifically, the mental demand component of the NASA-TLX. Results from this study may prove useful for designing curricula in anatomy education and improving training procedures for surgeons.

  8. Distribution and absorption of local anesthetics in inferior alveolar nerve block: evaluation by magnetic resonance imaging.

    Science.gov (United States)

    Ay, Sinan; Küçük, Dervisşhan; Gümüş, Cesur; Kara, M Isa

    2011-11-01

    The aim of this study was to evaluate the distribution and absorption of local anesthetic solutions in inferior alveolar nerve block using magnetic resonance imaging. Forty healthy volunteers were divided into 4 groups and injected with 1.5 mL for inferior alveolar nerve block and 0.3 mL for lingual nerve block. The solutions used for the different groups were 2% lidocaine, 2% lidocaine with 0.125 mg/mL epinephrine, 4% articaine with 0.006 mg/mL epinephrine, and 4% articaine with 0.012 mg/mL epinephrine. All subjects had axial T2-weighted and fat-suppressed images at 0, 60, and 120 minutes after injection. The localization, area, and intensity (signal characteristics) of the solutions were analyzed and onset and duration times of the anesthesia were recorded. There were no significant differences between groups with regard to the intensity and area of the solutions at 0, 60, and 120 minutes after injection, but differences were found within each group. No between-group differences were found on magnetic resonance imaging in the distribution and absorption of lidocaine with or without epinephrine and articaine with 0.006 and 0.012 mg/mL epinephrine. All solutions were noticeably absorbed at 120 minutes after injection. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation.

    Science.gov (United States)

    Fridman, Jordan S; Scherle, Peggy A; Collins, Robert; Burn, Timothy; Neilan, Claire L; Hertel, Denise; Contel, Nancy; Haley, Patrick; Thomas, Beth; Shi, Jack; Collier, Paul; Rodgers, James D; Shepard, Stacey; Metcalf, Brian; Hollis, Gregory; Newton, Robert C; Yeleswaram, Swamy; Friedman, Steven M; Vaddi, Kris

    2011-09-01

    JAKs are required for signaling initiated by several cytokines (e.g., IL-4, IL-12, IL-23, thymic stromal lymphopoietin (TSLP), and IFNγ) implicated in the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis (AD). Direct antagonism of cytokines, such as IL-12 and IL-23 using ustekinumab, has proven effective in randomized studies in psoriasis patients. We hypothesized that local inhibition of cytokine signaling using topical administration of INCB018424, a small molecule inhibitor of JAK1 and JAK2, would provide benefit similar to systemic cytokine neutralization. In cellular assays, INCB018424 inhibits cytokine-induced JAK/signal transducers and activators of transcription (STAT) signaling and the resultant production of inflammatory proteins (e.g., IL-17, monocyte chemotactic protein-1, and IL-22) in lymphocytes and monocytes, with half-maximal inhibitory concentration values keratinocyte proliferation in a murine contact hypersensitivity model and inhibited tissue inflammation induced by either intradermal IL-23 or TSLP. Topical INCB018424 was also well tolerated in a 28-day safety study in Gottingen minipigs. These results suggest that localized JAK1/JAK2 inhibition may be therapeutic in a range of inflammatory skin disorders such as psoriasis and AD. Clinical evaluation of topical INCB018424 is ongoing.

  10. Local Preparation and Evaluation of Double - antibody Liquid Phase Radioimmunoassay System for Detection of Human Testosterone

    International Nuclear Information System (INIS)

    Shafik, H.M.; Sallam, Kh.M.; Ebeid, N.H.; Elshaer, M.R.; Elshae, M.R.

    2016-01-01

    Preparation, evaluation and optimization of testosterone radioimmunoassay (RIA) system using liquid phase double antibody is considered to be the main objective. Three primary components were p